Biochemistry

Question 1

What is a cell?

Answer 1

Basic structural, functional and biological unit of all living organisms
Smallest unit of life replicate indecently
Require nutrients and produce waste

Question 2

Describe the cell membrane

Answer 2

Selectively permeable biological membrane separating interior and exterior of cell and protecting from surroundings
Involved in cell adhesion, ion conductivity, cell signalling, attachment surface for cell wall, glycocalyx (glycoprotein-polysaccharide surrounding CM of some bacteria and epithelial) and intracellular cytoskeleton

Question 3

Describe the phospholipid bilayer

Answer 3

Made of hydrophilic heads and hydrophobic tails
Phospholipids spontaneously form self-sealing bilayers
Due to hydrophobic interior charged ions cannot diffuse
Fluid - components move around easily
Mosaic - variety of lipids and proteins

Question 4

Describe centrosomes

Answer 4

Associated with nuclear membrane in prophase
In mitosis, NM breaks down and centrosome nucleated microtubules (cytoskeleton) interact with chromosomes to build mitotic spindle
Mother centrosome (oldest) role in making cilia and flagella

Question 5

Describe lysosomes

Answer 5

Membrane bound organelle that functions as recycling centre by digesting unwanted material in cytoplasm from extracellular and obsolete intracellular components
Contains hydrolytic enzymes capable of digesting almost all biomolecules: proteins, nucleic acids, carbs, lipids, debris
50+ enzymes all active at about pH 5

Question 6

Describe the cytosol/ICF

Answer 6

Liquid found inside cells separated into compartments by membranes i.e. mitochondrial matrix separates cells into compartments
Eukaryotes - ICF in CM and part of cytoplasm (mitochondria, plastids, organelles minus internal fluids and nucleus

Question 7

Describe the vacuole

Answer 7

Membrane bound organelle filled with water containing in/organic molecules (enzymes in solution), sometimes engulfed solids
Formed by fusion of multiple vesicles
Shape and function varies depending on needs and type of cell
Role in autophagy, balance between biogenesis and degradation, lysis and recycling of mis-folded proteins

Question 8

Describe mitochondria

Answer 8

Membrane bound organelles
Main functions are to produce ATP in TCA (respiration) and regulate metabolism
Role in - signalling through mitochondrial reactive O2 specifies
Regulate - MP, apoptosis, Ca signalling (including Ca-apoptosis), cellular metabolism, heme and steroid synthesis
Have oestrogen receptors (mtERs) thus sensitive to hormones
In liver cells, have enzymes that detoxify ammonia (waste product of protein metabolism)

Question 9

Describe the smooth ER

Answer 9

Site of lipid, phospholipid and steroid synthesis connected to nuclear envelope
Abundant in cells (ovaries, testes, skin oil glands) that secrete these products
Metabolism of carbs and steroids, drug detoxification, attachments of receptors on CMPs
Muscle cell - regulates Ca ion conc.

Question 10

Describe the cytoskeleton

Answer 10

Dynamic structure made of microfilaments (actin), microtubules (tubulin) and intermediate filaments (only found in animal cells) forming framework for movement of organelles and cell shape

Question 11

Describe the Golgi body

Answer 11

Modifies, sorts and packages macromolecules for exocytosis or use with in cell primarily those delivered by RER
Transports lipids and involved in creation of lysosomes
N/O-linked goycosylation

Question 12

Describe the rough ER

Answer 12

Complex responsible for manufacture of lysosomal enzymes (mannose-6-phosphate marker added in cis-Golgi network)
Manufacture of secreted proteins secreted either constitutively (no tag) or regulatory (clathrin and basic AA in signal peptide)
Initial stage of N-linked glycosylation

Question 13

Describe a vesicle

Answer 13

Variety of functions
Internal environment different from cytosolic as is separate from cytosol thus used for organising cellular substances
Involved in metabolism, transport, buoyancy control, enzyme storage (ready for immediate release), chemical reaction chambers

Question 14

Describe ribosomes

Answer 14

Site of gene translation
Attaches to mRNA, reads codon. tRNA with complementary anti-codon recruited bringing specific AA building protein.
Continues until reaches stop codon, if none will remain attached forming complex

Question 15

Describe the nucleus

Answer 15

Cell control centre: maintains integrity of genes and regulates gene expression
Contains DNA and histone proteins to form chromosomes
Has double membrane enclosing entire organelle isolating from cytoplasm, nuclear envelopes and nucleoskeleton (like cytoskeleton)

Question 16

Describe nucleolus

Answer 16

Organelle found in nucleus that forms around specific chromosomal a previous in nucleus
Made of proteins and RNA
Transcribe and modify rRNA and integrate ribosomal proteins into immature ribosomes
Stress sensor and able to regulate rRNA synthesis based on cell environment

Question 17

Describe the differences between prokaryotes and eukaryotes

Answer 17

Lack membrane bound nucleus (have nucleoid) and complex organelles
Ribosomal binding site in mRNA is the Shine Delgarno sequence: 8 bases up from AUG
Have mesosomes - folds inwards in PM that increase SA, can be artefact (damage to PM during chemical fixation)
Have cell wall, capsules and flagella (chemotaxis - movement of organism in response to chemical stimuli

Question 18

Describe gram +ve bacteria (purple)

Answer 18

Thick cell wall of peptidoglycan which is mesh that gives strength
Cell would be spherical and v sensitive to osmotic changes without

Question 19

Describe gram -ve bacteria (red)

Answer 19

Complex cell wall external to PM with thin peptidoglycan layer
Have outer membrane with lipopolysaccharides conferring
Structural integrity, resistance to chem. attack, toxicity (septic shock, death)

Question 20

How do many antibiotics work?

Answer 20

Act by inhibiting cell wall synthesis

B-lactam antibiotics (Penicillins) interfere with peptidoglycan synthesis causing cell lysis

Question 21

What is pH?

Answer 21

Logarithmic measure of conc. of H+ ions (protons) in solution
pH = -log[H+]

Question 22

What is the physiological pH of the body and why is this important?

Answer 22

pH 7.4
pH affects solubility of substances and the activity of biological systems thus keeping pH constant is important for body
Blood pH<7.3 acidosis
Blood pH>7.5 alkalosis

Question 23

Define acid, base, conjugated acid and conjugated base

Answer 23

Acid - proton donator, gains -ve charge
Base - proton acceptor, gains +ve charge
Conjugated acid - species formed from addition of H+
Conjugated base - what is left after acid donates proton

Question 24

What is the major respiratory acid in the body and how is it formed?

Answer 24

CO2
Dissolved in water forming carbonic acid which dissociates releasing H+
CO2 + H2O H2CO3 H+ + HCO3-

Question 25

Name some metabolic acids and how they produced

Answer 25

Organic (lactic, uric) and inorganic (sulphuric) produced by metabolism of AAs containing phosphorus and sulphur Lactic - product of anaerobic glycolysis Keto acids - ketoacidosis, lack of insulin Drugs - aspirin

Question 26

Define buffer

Answer 26

Solution that resists changes in pH when acid/alkali is added to it Usually a solution of weak acid and its conjugate base Biological fluids have ENDOGENOUS buffers

Question 27

How do buffers work?

Answer 27

Weak acid will partially dissociate and salt will fully dissociate allowing H+/OH- ions to be added and equilibrium will shift to replace the lost molecules As one fully dissociates more ions will be produced and not removed

Question 28

What are the main buffers in the body and where are they found?

Answer 28

Haemoglobin (HHb) found in red blood cells Proteins (HProt) in intracellular fluid Phosphate (H2PO4-) in intracellular fluid BICARBONATE (CO2->H2CO3) - blood plasma, interstitial fluid

Question 29

Define buffer capacity

Answer 29

Extent of resistance to pH change i.e. how much acid/base added before pH changes dramatically

Question 30

What is the dissociation constant?

Answer 30

Kd - Type of equilibrium constant that measures the dissociation of larger compound to split reversible to smaller components

Question 31

What is pK(a)?

Answer 31

The pH at which 50% of the HA (acid) has ionised

Question 32

What is the Henderson-Hasselbalch equation?

Answer 32

pH = pK + log[A-]/[HA]

Question 33

What is the relationship between pH, pKa and ionisation?

Answer 33

If the pKa is higher than pH, acid is less likely to be ionised

Question 34

What is critical pH?

Answer 34

pH at which tooth becomes unsaturated with respect to Ca and PO43- allowing hydroxyapatite in enamel to dissolve Region of pH 5.2-5.5

Question 35

How does saliva protect teeth from decay?

Answer 35

Produces many buffers (principally bicarbonate) which prevent resting pH falling much lower than pH 6.3

Question 36

What are the main buffers in saliva and how effective are they?

Answer 36

Proteins - not effective as nearly all charged groups from peptide bonds Phosphate - good but not in high enough conc. to be effective Bicarbonate - good

Question 37

What is the role of bicarbonate in plaque?

Answer 37

Acts to neutralise acid rather than buffer acid | Produces H+ pushing reaction to right producing CO2 and H2O - CO2 released as mouth open system

Question 38

What conc. does carbonic acid stay at in the mouth and what changes?

Answer 38

About 1.3mMol/L | pH and [HCO3-] change, bicarbonate varies with flow rate

Question 39

What must all AAs have?

Answer 39

Amino (NH2), carboxyl (COOH), H and R group | a-carbon is C atom amino and carboxyl groups are attached

Question 40

What is the role of side chains?

Answer 40

Are the functional groups Determine structure, function and charge of AAs Charged, polar or hydrophilic R groups exposed on surface Non-polar, hydrophobic R groups buried in interior

Question 41

What confers an AAs' optical activity?

Answer 41

An asymmetric C atom - C attached to 4 different groups | All AAs except GLYCINE (R group = H) are asymmetric

Question 42

What does being asymmetric mean?

Answer 42

Means compound has spatially distinct but chemically identical isomers that are mirror images of each other (enamtiomers) Both are optically active (rotate plane polarised light) to right (Dextro) or to left (Levo - majority of AAs)

Question 43

What is a zwitterion?

Answer 43

A molecule that bears groups of opposite polarity | As amino and carboxylic acid groups readily ionise AAs are dipolar/zwitterions

Question 44

How does the charge of AAs change with increasing pH?

Answer 44

Low pH - amino protonated, carboxyl normal pH 7 - amino protonated, carboxyl ionised High pH - amino normal, carboxyl ionised

Question 45

Define AMPHOTERIC

Answer 45

Molecules that have both acidic and basic groups | AAs are amphoteric

Question 46

Define anion

Answer 46

A negative ions from gain of e-

Question 47

Define cations

Answer 47

+ve charged molecule

Question 48

Name the aliphatic AAs? (Hydrophobic/non-polar) | VIGAL

Answer 48

``` V - valine I - isoleucine G - glycine A - alanine L - leucine ```

Question 49

Name the aromatic AAs | Y+T

Answer 49

Phenylalanine (phenol - aromatic) Tryptophan (Y + T = aromatic) Both non-polar Tyrosine (Y + T)

Question 50

Name the sulphur containing AAs | MC Sulphur

Answer 50

M - methionine C - cysteine (can from S-S, stabilise proteins) MC Sulphure

Question 51

Name the neutral polar AAs

Answer 51

Hydroxy-Soft Towel Serine Threonine Amide derivates of Acids Asparagine Glutamine

Question 52

What is the ImIno acid?

Answer 52

Proline - causes bends in polypeptides

Question 53

Name acidic AAs

Answer 53

Aspartic acid Glutamic acid COOH R group - ionised at pH 7

Question 54

Name the basic AAs | Larry is basic

Answer 54

L - lysine Ar - arginine His - histidine LArHis - extra +ve charge

Question 55

What formula is used to calculate the isoelectric point? How is this calculated for amino acids with 2 carboxyl/amino groups?

Answer 55

pI = (pKa + pKb)/2 a (acidic) = COOH b (basic) = NH2 For 2 carboxyl groups the (pKa1 + pKa2)/2 is used

Question 56

What is a dalton?

Answer 56

Da is a unit of molecular weight equivalent to 1 H atom | Compares how heavy something is to H

Question 57

Describe the primary structure of a protein

Answer 57

Unique sequence of AAs held by peptide bonds | Compare structure to find common sequences suggesting members of a multigene family

Question 58

Describe the secondary structure of proteins

Answer 58

H bonding determines secondary structure either a-helix or B-pleated sheet

Question 59

Describe boding in and structure of an a-helix

Answer 59

N atom in peptide bond shares H atom with CO group 4 residues upstream Polypeptide twists around in a spiral, each turn takes 3.6 AAs residues

Question 60

Describe B-pleated sheets

Answer 60

B strands laterally connected by 2/3 H bonds | Typically 3-10 AAs long

Question 61

Describe the tertiary structure of AAs

Answer 61

Folding of secondary requiring series of non-covalent interactions Held by electrostatic, VDWs, disulphide, hydrophobic interactions

Question 62

What are electrostatic bonds?

Answer 62

Strong interactions between ions/charged groups of opposite charge In protein called a salt bridge

Question 63

What are Van der Waals forces?

Answer 63

Weak, close range temporary dipole-dipole interactions

Question 64

What are disulphide bonds?

Answer 64

Strong covalent S-S bonds between specific cysteine residues Tend to lock molecule into configuration allowing it to withstand v high temperatures

Question 65

What are hydrophobic interactions?

Answer 65

Interactions between polar and non-polar molecules causing the spontaneous folding of hydrophobic residues away from water

Question 66

Describe the quaternary structure of proteins

Answer 66

Association of multiple tertiary polypeptides | Haemoglobin is association of 4 globin groups and 4 heme groups

Question 67

What is a protein domain?

Answer 67

Part of a polypeptide that can fold independently of polypeptide into compact, stable tertiary structure Usually identified by presence of prolIne Can be cut, isolated and studied separately from main chain

Question 68

What is protein folding?

Answer 68

Process by which higher structures are formed from primary (AA) sequence

Question 69

What are transitions in shape of tertiary or quaternary structures called?

Answer 69

Conformational changes - proteins may shift between several similar structures in performing their function (Tertiary and quaternary structures referred to as conformations)

Question 70

What is the reversible nature of protein folding dependent on?

Answer 70

Primary structure being maintained

Question 71

What are the three classes of proteins?

Answer 71

Fibrous Globular Membrane-associated

Question 72

Describe globular proteins

Answer 72

Are soluble, nearly all enzymes are globular | Carbonic anhydrase and haemoglobin are examples

Question 73

Describe carbonic anhydrase

Answer 73

Catalyses interconversion of CO2 + H2O to carbonic acid Different classes have little sequential or structural similarities but share identical AS thus all perform same function and require a Zn atom Contains large B sheet in centre

Question 74

Describe haemoglobin

Answer 74

Assembly of 4 globular protein subunits each composed of protein chain (2 a chains, 2 B chains) tightly associated with prosthetic heme group

Question 75

What is a prosthetic group?

Answer 75

Non-protein group tightly bound to protein that confers function Heme has an Fe atom held in heterocyclic ring equally to all 4 N atoms Fe is site of O2 binding

Question 76

Describe fibrous proteins

Answer 76

Form rod/wire like shapes, usually structural or storage proteins AA sequence often lacks repeating units From unusual 2ndary structures (collagen triple helix) due to cross-links between chains e.g. S-S bonds between keratin Usually used to construct CT, tendons, bone matrix, muscle fibre

Question 77

What are keratins and what do they form?

Answer 77

Family of fibrous structural proteins, they are tough and insoluble Form non-mineralised structures found in reptiles, birds, amphibians, mammals (hair)

Question 78

Describe the structure of keratin

Answer 78

High proportion of glycine (smallest) and alanine (2nd smallest) AAs High amounts of cysteine (sulphur containing) required for S-S bridges confer strength, rigidity by permanent, thermally stable cross-links

Question 79

Describe the structure of keratin monomer and the assembly into intermediate filaments

Answer 79

3 domains: head, rod, tail | Monomers associate to dimers, associate to tetramers, finally to intermediate filaments forming part of cytoskeleton

Question 80

What is collagen?

Answer 80

Family of fibrous proteins secreted by CTs with triple helix AA structure 28 different types Unique sequence of glycine-proline/hydroxyproline-alternative AA

Question 81

What are the 3 type of membrane-associated proteins?

Answer 81

``` Transmembrane (intrinsic) - cross membrane, usually a-helix Lipid associated (extrinsic) - bound to outer surface Proteins attached to transmembrane protein - increase ionic strength to detach i.e. add NaCl ```

Question 82

What are the 2 domains of membrane proteins?

Answer 82

Interdomain - intracellular | Outer domain - extracellular

Question 83

What are some of the functions of membrane proteins?

Answer 83

Transporters, linkers, receptors, enzymes

Question 84

Define enzyme

Answer 84

Proteins that catalyse biochemical reactions (biological catalysts)

Question 85

Define active site

Answer 85

Parts of enzyme that react with substrate (+ cofactors) in reaction

Question 86

Define co-enzyme

Answer 86

Small, diffusible organic residue that participates in enzyme catalysed reaction, is stable to heat

Question 87

Define prosthetic group

Answer 87

Coenzyme covalently bound to enzyme so that not removed by dialysis

Question 88

Define zymogen

Answer 88

Inactive precursor of enzyme

Question 89

Define holoenzyme

Answer 89

Protein (apoenzyme) with coenzyme/ions required for activity

Question 90

Define apoenzyme

Answer 90

Protein with coenzyme required for activity, liable to heat

Question 91

Define substrate

Answer 91

Molecule on which enzyme performs a reaction

Question 92

What is lysozyme?

Answer 92

An enzyme found in tissue fluids/secretions, tears, saliva, nasal mucus that protects against bacteria by causing cell to lyse and lose cell content

Question 93

What is peptidoglycan?

Answer 93

Polysaccharide formed from polymerisation of monosaccharides N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)

Question 94

Describe the structure of bacterial cell wall

Answer 94

Made of peptidoglycan - retains high internal osmotic pressure Layers of repeating peptidoglycan units with peptide chain bound to NAM Penta-glycine cross-links between last residue of chain and second last of opposite chain - added strength

Question 95

Describe alpha and beta linkages

Answer 95

Alpha: H atoms of the C atoms in bond in cis formation Beta: H atoms of C atoms in bond in trans formation

Question 96

Describe the lysis of the cell wall

Answer 96

Lysozyme hydrolyses B1:4 bond (between C1 and C4) in glycan between NAG and NAM Occurs rapidly at close to pH 7

Question 97

What else will lysozyme hydrolyse?

Answer 97

``` Oligo NAG (min 6 residues) Fit into groove round enzyme that closes on the strand ```

Question 98

What are serine proteases?

Answer 98

Enzymes with hyperactive serine residue at active site and appropriately spaced histidine and aspartate resides

Question 99

Name some serine proteases

Answer 99

Trypsin Chymotrypsin Elastase Thrombin

Question 100

How do serine proteases work?

Answer 100

Catalyse by breaking peptide bond using charge relay system

Question 101

Describe the charge relay system

Answer 101

Flow of electrons between 3 AAs making serine hyperactive | AAs are far apart in primary structure but close in 3D structure due to protein folding

Question 102

Why are proteolytic enzymes secreted as zymogens?

Answer 102

As are hazardous to body so secreted as zymogens that are activated in gut lumen

Question 103

Give examples of proteolytic enzymes

Answer 103

Pepsinogen Tryspinogen Chymotrypsinogen

Question 104

Describe the activation of pepsinogen

Answer 104

Chief cells in gastric gland produce pepsinogen Parietal cells produce HCl hydrolyses some peptide bonds to produce pepsin Left over pepsinogen is hydrolysed again to produce more pepsin

Question 105

Describe the activation of trypsinogen

Answer 105

Pancreatic duct secretes pancreatic zymogens Some zymogens converted to trypsinogen which is converted to trypsin by enterokinase (produced by brush border) Trypsin activates more enzymes such as chymotrypsinogen

Question 106

Describe the activation of chymotrypsinogen

Answer 106

Inactive state: single polypeptide, 245AAs with 5 SS bridges, three portions of AS caN'T come together Trypsin cuts bond between Arg15 and next residue - pi-chymotrypsin left Cut at Leu13 removes dipeptide bond Cut at Tyr146 and Asn148 removes another - a-chymotrypsin 3 parts held by SS bridges Active site resides come together Charge transfer complex with hyperactive serine formed

Question 107

How is specificity of enzymes dictated?

Answer 107

Pocket close to AS into which an AA side chain may fit thus size and nature of pocket are important

Question 108

Describe the specificity of trypsin, chymotrypsin and elastase

Answer 108

Trypsin: cuts basic R groups; Asp at bottom of pocket Chymotrypsin: cuts hydrophobic R; hydrophobic pocket Elastase: cuts small R; small pocket

Question 109

Describe the steady state hypothesis

Answer 109

In enzyme catalysed reaction, enzyme and substrate form complex which is a transient state (either breaking down or reversing) Initially conc. of complex will increase but will become steady as when broken down enzyme will form new complex

Question 110

What is Vmax?

Answer 110

The velocity a reaction approaches as substrate conc. is increased

Question 111

What is Michaelis constant (Km)?

Answer 111

Substrate conc. at 1/2Vmax Dependent on substrate and enzyme Measures affinity of enzyme for substrate - a high Km confers low affinity

Question 112

What is the relationship between substrate conc. and velocity?

Answer 112

Michaelis-Menten equation v = Vmax[S]/(Km+[S]) When [s]=Km v = 1/2Vmax When [s]>>Km v ~ Vmax

Question 113

What is the importance of Km?

Answer 113

Can use to compare 1 enzyme's affinity for different substrates or Multiple enzymes affinities' for 1 substrate

Question 114

Describe hexokinase

Answer 114

Phosphorylates glucose Widespread in tissue Low Km = high affinity Always active

Question 115

Describe glucokinase

Answer 115

Found in liver and pancreas High Km = low affinity only active at high glucose conc. At high conc. glucose stored in liver as glycogen, insulin produced by pancreas

Question 116

Explain the influencing factors of enzymes

Answer 116

Optimum temp. and pH range above optimum will denature and activity will suddenly drop Increasing temp. increases energy of collisions, internal energy of reactants and number of collisions

Question 117

What are lipids?

Answer 117

``` Diverse class of insoluble compounds that don't form polymers Are hydrophobic (mostly hydrocarbons) and soluble in organic solvents (ether, acetone, chloroform) ```

Question 118

Give examples of lipids

Answer 118

Fats, oils, fatty acids, triacylglycerols, glycolipids, phospholipids, steroids

Question 119

What is the main function of fatty acids?

Answer 119

Catabolised generating ATP or used to synthesise triglycerides and phospholipids

Question 120

Main function of triglycerides?

Answer 120

Energy storage, protection, insulation

Question 121

Phospholipids main function?

Answer 121

PM

Question 122

Main function of steroids

Answer 122

Component of many hormones, cholesterol

Question 123

Describe the structure of fatty acids

Answer 123

Long hydrocarbon chain with terminal carboxylic acid group Hydrocarbon chain: saturated (no double bonds), monounsaturated (1 C=C), polyunsaturated (2+ C=C) Unsaturation causes kink in chain All naturally occurring unsaturated fats are in cis formation whereas trans unsaturated fats found in manufacture of food

Question 124

Compare saturated and unsaturated fats

Answer 124

Palmitic (C16) is a saturated fat, MP 69.9 Oleic (C18) is monounsaturated, MP 13.4 - C=C makes packing of molecule difficult Most animal fats are saturated whereas most fish and plant fats are unsaturated

Question 125

What is glycerol and what is its importance?

Answer 125

Three C substance that forms backbone of fatty acids in fats | Important component of triglycerides and phospholipids

Question 126

What is triglyceride and describe its structure

Answer 126

Main component of vegetable oil and animal fats formed from the esterification of 3 fatty acids with glycerol Has chemical structure CH2COOHR-CHCOOHR'-CH2COOHR"; Rs are long alkyl groups The fatty acids can be all same, different or 2 the same

Question 127

What is the importance of triglycerides?

Answer 127

Metabolism: contain 2X energy as carbs and proteins Storage and transport form of fats High levels linked to atherosclerosis (heart disease, stroke)

Question 128

What is the role of adipocytes and adipose tissue?

Answer 128

Adipocytes specialised for synthesis and storage of triglycerides Found in subcutaneous layer and in abdominal layer Subcutaneous fat provides insulation

Question 129

What is lipolysis?

Answer 129

Breakdown of triglycerides into glycerol and fatty acids with release of energy Fatty acids released into blood, circulate body

Question 130

Describe the catabolism of glycerol

Answer 130

Converted to glyceraldehyde 3-P and then glucose OR enter TCA depending on ATP supply

Question 131

Describe the catabolism of fatty acids

Answer 131

Enzymes remove 2C atoms at a time to acetyl CoA to enter TCA

Question 132

Describe the process of FA activation

Answer 132

Acetyl-CoA synthases esterify long chain FAs to acyl-CoA | Is ATP dependant

Question 133

Describe the process of FA oxidation

Answer 133

Acyl-CoA dehydrogenase removes H2 from acyl-CoA, NAD is reduced to NADH2, acetyl-CoA oxidised to trans-enoyl-CoA enoyl-CoA hydratase, hydrates trans-enoyl-CoA to B-hydroxyacyl-CoA B-hydroxyacyl-CoA dehydrogenase oxides B-..-CoA to B-ketoacyl-CoA Acyl-CoAacetyl-transferase moves acetyl forming acyl-CoA (2Cs shorter) + acetyl-CoA

Question 134

What is lipogenesis?

Answer 134

Synthesis of lipids (anabolism) from smaller units Mainly occurs in liver and adipose tissue in conditions of excess sugar as glucose converted to glycogen It doesn't appear to be essential

Question 135

Compare glucose and fructose

Answer 135

Glucose used in cells throughout body, fructose only in liver Glucose converted to glycogen, some to FAs and triglycerides Fructose converted to acetyl them FAs and triglycerides

Question 136

What are essential fatty acids?

Answer 136

FAs that are required in human diet as humans lack specific enzyme so cannot be synthesised by the body

Question 137

What can a deficiency of a-linoleic acid and linoleic acid lead to?

Answer 137

Dry scaly rash, decreased growth (children/infants), susceptibility to infection, poor wound healing Present in variety of foods, represent omega 3 and 6 category of lipid structure

Question 138

Describe the structure of phospholipids

Answer 138

2 FAs and P group attached to glycerol | FAs from hydrophobic tail, P and its attachment form hydrophilic head

Question 139

What is meant by amphipathic?

Answer 139

Molecule with both hydrophobic and hydrophilic groups

Question 140

Describe saturation in phospholipids

Answer 140

1 chain saturated, other not | Degree of saturation alters ability of molecules to pack, affects fluidity

Question 141

What is the function of cholesterol?

Answer 141

Controls permeability of membrane | Makes membrane less flexible due to rigid steroid ring

Question 142

Describe glycolipid structure

Answer 142

2 hydrophobic tails, hydrophilic region with 2+ sugar residues i.e. phospholipids without P

Question 143

What is the function of glycolipids?

Answer 143

Make up 5% of outer monolayer Sugar groups exposed on cell surface protect and modulate membrane function Insulating agents in nerve cells (gangliosides)

Question 144

Describe the structure of steroids

Answer 144

Lipids characterised by C skeleton of 4 fused rings

Question 145

What is the role of steroids?

Answer 145

Cholesterol: high levels cause atherosclerosis Hormones: testosterone, oestrogen, cortisol (synthesised from cholesterol) control metabolism, development of sexual characteristics, immune functions

Question 146

What is a lipoprotein?

Answer 146

Biochemical assembly that contains both proteins and lipids

Question 147

What is the function of lipoproteins?

Answer 147

Transport insoluble lipids in plasma | Non-polar lipids (triglycerides) contained in hydrophobic centre, polar lipids (phospholipids) form coat

Question 148

What are apoproteins?

Answer 148

Protein components of lipoproteins | Interact with cellular receptors and determine the metabolic fate of lipoproteins

Question 149

Explain LDL and HDL

Answer 149

LDLs carry FAs in blood for use by cells but also deposit on artery walls (bad) HDLs carry LDLs away from artery walls (good)

Question 150

What are some of the ways to treat hypercholesrerolemia?

Answer 150

Reduce intake (egg yolk, liver, oily fish) Reduce absorption uptake - zetia, ezetro, niacin Statins - block enzyme in synthesis of cholesterol

Question 151

What are the 2 classifications of carbs?

Answer 151

Simple - monosaccharides | Complex - disaccharide, oligosaccharide(2+), polysaccharide (many)

Question 152

Describe monosaccharides

Answer 152

Simple sugars: can't be converted into smaller molecules by acid hydrolysis 1 sugar, usually colourless, water-soluble, crystalline solids Building blocks of di and polysaccharides

Question 153

Describe the structure of monosaccharides

Answer 153

Generally have formula (CH2)n - deoxyribose is an exception Simple monosaccharides C4-7 called tetroses, pentoses, hexoses, heptoses Exceptions in animals N-acetyl sugars (8C), sialic acid (9,10,11C)

Question 154

What are 2 classifications of monosaccharides?

Answer 154

Aldose and ketose Aldose - -CHO (aldehyde group) Ketose - C=O (ketone group) e.g. aldopentose or ketopentose

Question 155

Describe the structure of glucose in both straight chain and ring

Answer 155

``` C6H12O6 Is an aldose sugar i.e. has -CHO Ring: C1 binds to C5 - C1-O-C5 O enables C atoms to bind to from ring H from C5 OH binds to O on C1, C1 binds to O ```

Question 156

Describe the structure of fructose

Answer 156

C6H12O6 Is a ketose i.e. has C=O on C2 Ring: C2 bonds to C5 H of C5 OH binds to O of C2, C2 binds to O on C5

Question 157

What is stereochemistry?

Answer 157

Study of spatial 3D relations of atoms in molecules

Question 158

What are Fischer projections?

Answer 158

Basic 2D drawing of 3D molecule C1 is always at top Projections drawn to left are ABOVE the ring Projections to right are BELOW the ring

Question 159

Explain D and L sugars

Answer 159

D and L sugars are optical isomers (mirror images of each other) D and L refer to the absolute configuration of asymmetric C furthers away from aldehyde/ketone group OR if OH falls on either LHS/RHS D-glucose is biologically active, OH of C5 falls on RHS

Question 160

What is the structure of D-glucose?

Answer 160

OH of C2,4,5 to right OH of C3 to left L-glucose is opposite

Question 161

What happens in solution of glucose in terms of structure?

Answer 161

Equilibrium favouring ring form established Ring formation creates new chiral centres - C1 in aldoses, C2 in ketoses This increases the number of possible isomeric forms

Question 162

What are isomers of D-glucose called?

Answer 162

Anomers

Question 163

Describe the 2 anomers of D-glucose

Answer 163

Alpha - (new) OH of C1 is TRANS to CH2OH on C5 | Beta - OH of C2 is CIS to CH2OH on C5

Question 164

What is mutarotation?

Answer 164

Interconversion between anomer stereoisomers | Different anomers have different optical rotations

Question 165

What are monosaccharide derivatives?

Answer 165

Simple sugar molecules which contain functional groups as well as OH, either CHO/CO, vary from empirical formula

Question 166

Describe deoxy derivatives

Answer 166

OH replaced by H | e.g. deoxyribose sugar - ribose with OH on C2 replaced by H

Question 167

Describe sugar acid derivatives

Answer 167

OH group oxidised to COOH

Question 168

Describe sugar alcohol derivatives

Answer 168

CO (aldehyde or ketone) reduced to primary/secondary OH

Question 169

Describe phosphorylated sugars

Answer 169

P group attached | Alcoholic group esterified with phosphoric acid

Question 170

What are amino sugars?

Answer 170

Sugar with primary amine group replacing OH | e.g. glucosamine precursor for GAGs (major component of joint cartilage) thus used to treat osteoarthritis

Question 171

Explain the formation of disaccharides

Answer 171

Aldehyde/ketone group reacts with molecules own OH to form ring, then link to C bearing OH on another sugar molecule creating a disaccharide

Question 172

How are monomers linked?

Answer 172

Glycosidic bonds formed when anomeric OH group condenses with alcohol of second monosaccharide Catalysed by hydrolyse (dehydration) to form R-O-R link

Question 173

Describe the structure of sucrose

Answer 173

Glucose and fructose monomers linked by alpha 1,2 linkage

Question 174

What is glycogen?

Answer 174

Polysaccharide that is the principal storage form of glucose found as granules in cytosol Liver cells have highest conc. but muscles have greater total amount

Question 175

Describe the structure of glycogen

Answer 175

``` Highly branched (increases packing) Linear chains of glucose connected by a-1,4 glycosidic linkages with branches attached through a-1,6 links every 10 residues ```

Question 176

What 2 enzymes are required for glycogen degradation and why?

Answer 176

Glycogen phosphorylase to hydrolyse a-1,4 linkages but can only work on linear chains OR a-amylase (digestive) Debranching enzyme to hydrolyse a-1,6 links to straighten out chain

Question 177

Describe the degradation of glycogen

Answer 177

Glycogen phosphorylase breaks glycogen into glucose-1-P but is halted 4 residues from branching point Glycogen debranching enzyme transfers trisaccharide to a-1,4 adjacent a-1,4 link leaving single glucose molecule at a-1,6 GDE hydrolyses remaining glucose molecule so glycogen phosphorylase can continue

Question 178

Describe the structure of starch

Answer 178

(C6H10O5)n 2 polysaccharides monomers: amylose, amylopectin Amylose: glucose monomers linked by a-1,4 links Amylopectin: coiled structure, like glycogen but a-1,6 branch every 24-30 residues

Question 179

What is the function of starch?

Answer 179

Digested by hydrolysis, catalysed by amylases, back to sugar monomers which can be broken down to glucose for energy

Question 180

What is cellulose?

Answer 180

Polymeric polysaccharide of B-glucose monomers

Question 181

What is the function of cellulose?

Answer 181

Primary structural component of cell wall of green plants Lignin and cellulose (lignocellulose) most common biopolymer on earth Only tunicates evolved the ability to create and use cellulose Indigestible by humans so acts as hydrophilic bulking agent for faeces

Question 182

Describe the structure of cellulose

Answer 182

Layered linear chains of B-1,4 linked D-glucose units packed into crystals (myofibrils) Layers linked by H bonds

Question 183

What is lactose?

Answer 183

Disaccharide of B-D-galactose and B-D-glucose linked through B-1,4

Question 184

What are glycosaminoglycans? (GAGs)

Answer 184

Large, pure carbohydrates that are -ve charged, hydrophilic | Polysaccharides present on animal cell surface and in ECM

Question 185

Describe the structure of GAGs

Answer 185

Disaccharide repeating unit containing glucosamine or galactosamine and uronic acid At least one of the sugars has a -ve charged carboxylate or sulphate group - with exception of hyaluronic acid (no sulphate group)

Question 186

What is a glycoprotein?

Answer 186

Macromolecule composed of protein and a carbohydrate which is added in posttranslational modification either at asparagine (N-glycosylation) or hydroxylysine/hydroxyproline/serine/threonine (O-glycosylation)

Question 187

What is the function of glycoproteins?

Answer 187

Assist protein folding or improve stability Immune cell recognition: antibodies (immunoglobulins) interact directly with antigens, moles of major histocompatibility complex (MHC) surface of cells interact with T-cells (adaptive immune response)

Question 188

Explain N and O glycosylation

Answer 188

Glycosylation is the attachment of carbohydrate to AA side chain N: attach to N of amide side chain (asparagine) O: attach to O of OH side chain (hydroxylysine/hydroxyproline/serine/threonine)

Question 189

What are proteoglycans?

Answer 189

Heavily glycosylated glycoproteins - core protein with several GAG chains

Question 190

What are the functions of GAGs?

Answer 190

Structural: ECM and BM Space-filling in cartilage Modifiers/activators of effector proteins (growth factors, proteases)

Question 191

What are the functions of proteoglycans?

Answer 191

Form large complexes in ECM with proteoglycans and fibrous matrix proteins (collagen) Binding of cations and water Regulation of movement of molecules through matrix

Question 192

What is chondroitin sulphate?

Answer 192

Sulphate GAG composed of N-acetyl-galactosamine and glucuronic acid Usually forms part of a proteoglycan

Question 193

What is the function of chondroitin sulphate?

Answer 193

Major structural component in cartilage conferring resistance to compression Dietary supplement for treatment of osteoarthritis

Question 194

What is heparin?

Answer 194

Highly sulphated GAG used as injectable anticoagulant and used for inside of test tubes, renal dialysis machines

Question 195

Describe the structure of peptidoglycan

Answer 195

Crystal lattice of linear chains of NAG and NAM Each NAM has peptide chain usually containing AAs that do not occur in humans thought to protect against attacks by most peptidases

Question 196

Describe the energy balance in humans

Answer 196

Balance between energy intake and energy expenditure

Question 197

Describe the anabolism of glucose

Answer 197

Glucose enters cell, undergoes glycogenesis forming glycogen in liver and muscle cells OR undergo lipogenesis and join FA chain

Question 198

Describe the anabolism of FAs

Answer 198

FAs esterified to triglycerides in adipose tissue

Question 199

Describe the anabolism of AAs

Answer 199

AAs undergo protein synthesis to form proteins in muscle

Question 200

Describe the metabolism of glycogen

Answer 200

Glycogen undergoes glycogenesis forming glucose, undergoes glycolysis to pyruvate converted to acetyl-CoA enters TCA

Question 201

Describe metabolism of triglycerides

Answer 201

Undergo lipolysis forming FAs, undergo B-oxidation to form acetyl-CoA enter TCA

Question 202

Describe protein metabolism

Answer 202

Proteolysis converts to AAs either directly enter TCA or converted to acetyl-CoA

Question 203

Describe glycogen stores and their mobilisation

Answer 203

In liver glycogen converted to glucose-6-P which is converted to glucose which can enter brain or back to glucose-6-P and used by muscles to produce lactate Muscle cells produce glucose 6P then lactate

Question 204

Describe the cori cycle

Answer 204

Lactate produced in muscle cell converted to pyruvate which can enter gluconeogensis to re-form glucose which can be recycled

Question 205

Describe lipid stores and mobilisation

Answer 205

Triglyceride stored in adipose broken down to glycerol and FAs Glycerol undergoes gluconeogenesis forming glucose, enters brain FAs enter muscle or undergo ketogenesis forming ketone bodies utilised by brain or enter muscle

Question 206

Describe protein utilisation

Answer 206

Undergo proteolysis produce AAs which can enter TCA, converted to Acetyl-CoA or undergo transamination (amino group moved) Acetyl-CoA enter TCA or converted to ketone bodies After transamination form pyruvate either enter TCA or gluconeogenesis

Question 207

Describe glucose transport

Answer 207

Enters cells via facilitated diffusion by GLUTs | Uptake increased by increasing GLUTs in PM - insulin or exercise

Question 208

Describe FA transport

Answer 208

Thought to diffuse across PM or may involve FA transporter proteins

Question 209

How is energy stored in cells?

Answer 209

In chemical bonds | When cell has enough energy available it stores it by adding Pi group to ADP forming ATP

Question 210

What are the stages of ATP production?

Answer 210

Digestion Glycolysis TCA

Question 211

Describe digestion

Answer 211

Food stuff digested HCl in stomach Enzymes - mouth, stomach, small intestine Enzymes in lysosomes for internal cell digestion Absorption through cells in SI, enter bloodstream then cells

Question 212

Describe glycolysis

Answer 212

Starts in cytoplasm Glucose broken down to 2 pyruvate molecules 2ATP and NADH produced per pyruvate Pyruvate molecules move to mitochondria where converted to CO2 and 2C acetyl group which attaches to CoA

Question 213

Describe the structure of CoA

Answer 213

8 trimers of lipoamide reductase-transacetylase 6 dimers of dihydrolipoyl dehydrogenase 12 dimers pyruvate decarboxylase

Question 214

What are the functions of the three enzymes in CoA?

Answer 214

Pyruvate decarboxylase - removes CO2 Lipoamide reductase transacetylase - transfer acetyl group Dihydrolipoyl dehydrogenase - reduces NAD

Question 215

What happens in glycolysis in anaerobic conditions?

Answer 215

Fermentation Muscle: pyruvate reduced to lactate reforming NAD+ Yeast: pyruvate reduced forming CO2 and acetaldehyde which is reduced to ethanol reforming NAD+

Question 216

Describe stage 3 of ATP production

Answer 216

Acetyl group enters TCA where it is oxidised to CO2 and large amounts of NADH generated NADH passed along electron transport chain where energy released produces ATP and consumes O2

Question 217

What is oxidative phosphorylation?

Answer 217

ATP formation driven by transfer of electrons from food molecules to molecular O2 Electron ends up on O2, with H+ H2O formed

Question 218

Name the 4 complexes of the electron transport chain

Answer 218

1. NADH dehydrogenase 2. Succinate dehydrogenase 3. Coenzyme Q reductase 4. Cytochrome c reductase

Question 219

What are the roles of the complexes in electron transport chain?

Answer 219

NADH dehydrogenase, succinate dehydrogenase, coenzyme Q reductase pump protons across membrane into intermebrane space making intermembrane increasing acidic Cytochrome c reductase give electron to O2 producing H2O

Question 220

How does the electron transport chain produce ATP?

Answer 220

Due to the high H+ conc. in intermembrane space, protons diffuse down conc. gradient through ATP synthase producing lots of ATP

Question 221

Name and describe the inhibitors of electron transport chain

Answer 221

Rotenone: blocks NADH from being oxidised by NADH dehydrogenase Antimycin A: blocks complex 2 CN or CO: prevent O2 being reduced by cytochrome c reductase

Question 222

What is the role of reactions?

Answer 222

Create order within cells: smaller molecules used to make macromolecules

Question 222

Define catabolism and anabolism

Answer 222

Catabolism: break down of molecules releasing energy Anabolism: construction of complex molecules from simple ones, storage of energy

Question 223

Define free energy

Answer 223

Gibbs free energy (G): measure of energy contained in a molecule due to vibration, rotation, bonds

Question 224

What is delta G?

Answer 224

Changes/difference in free energy | DG = G(products p) - G(reactants)

Question 225

Define exergonic and endergonic

Answer 225

Exergonic: releases energy to surroundings -DG Endergonic: absorbs free energy +DG

Question 226

Define activation energy

Answer 226

Energy difference between reagents and transition state i.e. energy required for reaction to progress

Question 227

How do enzymes work in terms of EA?

Answer 227

Lower the EA allowing larger proportion of random collisions with surrounding molecules to push substrate over EA

Question 228

How do enzymes work?

Answer 228

Bind substrate tightly holding it in a way that facilitates conversion to product

Question 229

Explain coupled reactions

Answer 229

Favourable (oxidisation of glucose) reactions release energy which is captured in chemical form and used to power unfavourable reactions (forming peptide bond) Favourable reactions take place spontaneously whereas unfavourable only occur if coupled

Question 230

What are carrier molecules?

Answer 230

Small proteins that contain 1+ energy-rich covalent bond and diffuse rapidly throughout cell thus carry bind energy from generation to utilisation

Question 231

How do carrier molecules (coenzymes) store their energy?

Answer 231

In easily transferable groups/high-energy electron (easily oxidised/reduced) - ATP, NADH, NADPH

Question 232

Describe the synthesis of a polynucleotide

Answer 232

Nucleoside monophosphate activated by sequential transfer of terminal P from 2 ATP High energy intermediate (nucleoside triphosphate) exists freely until reacts with growing end of R/DNA releasing pyrophosphate Hydrolysis of pyrophosphate to Pi highly favourable, drives overall reaction

Question 233

Explain the limits of ATP

Answer 233

DG of ATP is -7.3kcal/M only drive reaction up to that amount If reaction requires more ATP hydrolysis altered to produce AMP and PPi (pyro) which is hydrolysed producing large amounts of free energy

Question 234

What is the importance of enzyme inhibitors?

Answer 234

Info about shape of AS and AA residues at AS Info about chemical mechanism Info about regulation/control of metabolic pathway Aide drug design

Question 235

What are the 2 broad classifications of inhibitors?

Answer 235

Reversible Irreversible: usually involves formation or breaking of covalent bonds - enzyme forms covalent bond with AS so cannot be removed

Question 236

What are the 3 types of reversible inhibitors?

Answer 236

Competitive Non-competitive Uncompetitive

Question 237

Explain irreversible inhibition

Answer 237

Inhibitor forms covalent bond with AS of enzyme so is permanently attached thus permanently inactivates enzyme e.g. diisopropylphosphofluoridate prototype for nerve gas sarin, permanently inactivates serine proteases

Question 238

Explain competitive inhibition

Answer 238

Inhibitor competes with substrate to bind on AS Inhibitor and substrate have similar structures ONLY binds to enzyme NOT ES complex

Question 239

Explain the effect of competitive inhibitors on Vmax and Km

Answer 239

Reduces amount of free enzyme available for substrate binding (forms EI complex) thus Km increased, Vmax unchanged but requires more substrate to reach

Question 240

Give an example of competitive inhibition

Answer 240

Succinate is converted to fumarate by succinate dehydrogenase Malonate is a competitive inhibitor for this reaction

Question 241

How is competitive inhibition reversed?

Answer 241

Increase conc. of substrate to overcome reduced affinity

Question 242

Explain non-competitive inhibition

Answer 242

Inhibitor binds to separate, distinct binding site causing SLIGHT conformation change Can bind to E or ES and from ESI complex which is inactive

Question 243

Explain the effect on Vmax and Km of non-competitive inhibition

Answer 243

As substrate can still bind Km remains constant | As ESI inactive Vmax reduced

Question 244

Give an example of non-competitive inhibition

Answer 244

Fructose-1,6-diphosphate converted to fructose-6-phosphate by fructose-1,6-bisphosphatase which is inhibited by AMP (binds to separate site) and no fructose-6P produced

Question 245

Explain uncompetitive inhibition

Answer 245

Binding of substrate allows inhibitor to bind forming inactive ESI complex Inhibitor ONLY binds to ES

Question 246

Explain the effect of uncompetitive inhibition on Vmax and Km

Answer 246

Vmax decreased as enzyme inhibited | Km also reduced as creates better ES binding as only binds to ES (due to equilibrium and Le Chatelier's Principle)

Question 247

What are allosteric modulators?

Answer 247

Substances which can regulate enzyme activity

Question 248

Explain the 2 types of allosteric modulators

Answer 248

Positive: increase enzyme activity, binds to allosteric site causing conformational change to enhance substrate binding Negative: decrease activity, binds to site causing conformational change to decrease substrate binding

Question 249

What 2 hormones are responsible for regulation of glucose levels?

Answer 249

Insulin: promotes uptake and conversion to glycogen Glucagon: promotes breakdown of stored glycogen to glucose

Question 250

Name the 2 conditions caused by excess and lack of glucose

Answer 250

Hyperglycaemia: excess glucose, hallmark of diabetes, glucosuria (glucose toxicity) Hypoglycaemia: lack of glucose, loss of cognitive function, coma, permanent brain damage

Question 251

How is glucose transported into cells in the body?

Answer 251

Intestine: uptake from lumen to epithelial requires active transport Body: blood to cells (muscle, liver, adipose) passive or facilitated diffusion

Question 252

How is glucose uptake mediated?

Answer 252

GLUT transporters mediate glucose transport into liver, adipose, muscle tissues

Question 253

Describe GLUTS 1-4

Answer 253

GLUT1+3: PM throughout body, low Km 1mM (high affinity), maintain basal blood glucose 3-6mM GLUT2: liver, pancreatic cells, high Km 15-20mM, (low affinity as liver stores, pancreas produces insulin in high conc) GLUT4: muscle, adipose, low Km, insulin sensitive (phosphorylated by Metformin (anti-diabetic) increasing insulin sensitivity)

Question 254

How is glucose uptake regulate by insulin and exercise?

Answer 254

Uptake into muscle and adipose increased by insulin which increases no. of GLUT4 transporters in PM (GLUT4 containing vesicles fuse with PM) Insulin resistance associated with fewer GLUT4 transporters Exercise recruits GLUT4 transporters to PM in muscle

Question 255

Describe the alternative fates of glucose

Answer 255

Converted to glucose-6P either enter pentose phosphate pathway produce 5C sugar OR glycolysised to pyruvate (gluconeogenesis reproduce glucose-6P)

Question 256

Explain the role of hexokinase in glycolysis

Answer 256

Found in most cells throughout body, phosphorylates glucose to glucose-6P (1st step of glycolysis) Low Km Allosteric inhibition by own product (glucose-6P) Inhibition of HK causes increase in intracellular glucose inhibiting GLUT transporter

Question 257

Explain the role of glucokinase in glycolysis

Answer 257

Phosphorylates glucose in liver and pancreatic B cells Higher Km - only active when glucose levels are high In B cells acts as glucose sensors for insulin secretion Not inhibited by glucose-6P

Question 258

Outline the 10 steps of glycolysis

Answer 258

``` G-glucose G-glucose-6P F-fructose-6P F-fructose-1,6-bisphosphate G-glyceraldehyde-3P (+ dihydroxyacetone-P) G-glyceraldehyde-3P B-1,3-bisphosphoglycerate P-3-phosphoglycerate P-2-phosphoglycerate P-phosphoenolpyruvate P-pyruvate ``` ``` H-hexokinase P-phosphoglucose isomerase P-phosphofructokinase A-aldolase T-triosephosphate isomerase G-glyceraldehyde-3P dehydrogenase P-phosphoglycerate kinase P-phosphoglycerate mutase E-enolase P-pyruvate kinase ```

Question 259

Explain how phosphofructokinase 1 regulates glycolysis

Answer 259

High ATP conc. allosterically inhibits PFK1 by binding, promotes tense conformation with low affinity for fructose-6P PFK2 convert fructose-6P to fructose-2,6-bisP (+ ADP) high levels of fructose-2,6-bisP relieves inhibition High levels of citrate (1st intermediate TCA) inhibits as confers ATP already present ADP, AMP(extensive ATP hydrolysis) relieve inhibition

Question 260

Define kinases and mutases

Answer 260

Kinase: phosphorylates i.e. transfers PO4 from ATP to substrate Mutase: transfer PO4 from 1C to another within molecule

Question 261

Describe fermentation

Answer 261

Anaerobic organisms lack respiratory chain, NADH reoxidised as pyruvate converted to more reduced compound Some organisms convert pyruvate to ethanol oxidising NADH in reaction catalysed by alcohol dehydrogenase

Question 262

Explain how NADH enters the matrix of mitochondria

Answer 262

Oxaloacetate reduced to malate oxidising NADH Malate enters matrix is oxidised to oxaloacetate reducing NAD+ Oxaloacetate converted to aspartate by glutamate forming a-ketoglutarate Aspartate leaves matrix, reacts with a-ketoglutarate reforming oxaloacetate and glutamate

Question 263

Describe galactose metabolism

Answer 263

Gladstone phosphorylated to galactose-1P by galactokinase UDP-glucose reacts with galactose-1P converting to glucose-1P and forming UDP-galactose Glucose-1P P group moved by phosphoglucomutase to glucose-6P

Question 264

What is the importance of Ca?

Answer 264

Bone: provide structural integrity of skeleton | Biochemical processes: neuromuscular excitability, blood coagulation, hormonal secretion, enzymatic regulation

Question 265

Why must Ca conc. be maintained?

Answer 265

As has role in so many processes extra and intracellular conc. must be maintained

Question 266

Describe the regulation of intracellular [Ca]

Answer 266

Stored in mitochondria and ER 'Pump-leak' transport system: Ca leaks into cytoplasmic compartment, actively pumped into storage sites in organelles to shift away from cytosolic pools

Question 267

What are the 3 fractions of Ca in serum?

Answer 267

Ionised - 50% Protein-bound - 40% Complexed to serum constituents - 10%

Question 268

What protein is the majority of protein-bound Ca bound to?

Answer 268

Albumin -90%, binding is pH dependent | Rest is bound to globulins

Question 269

What 2 molecules is Ca complexed to?

Answer 269

Citrate | Phosphate

Question 270

Describe the effect of acute alkalosis on Ca binding

Answer 270

Inc. Ca binding, dec. ionised Ca | Causes inc. neural excitability and prone to seizures due to low ionised Ca in ECF causing inc. permeability to Na+

Question 271

Describe Ca turnover

Answer 271

1000mg intake 350mg absorption to ECF (1000mg) and exchangeable pool (4000mg) 500mg used and retrieved in bone remodelling 1000000mg stored in skeleton 200mg excreted in urine 150mg secreted into gut 800mg excreted in faeces

Question 272

What factors determine the conc. of serum Ca?

Answer 272

Intestinal absorption, renal excretion, bone remodelling

Question 273

Explain +ve and -be Ca balances

Answer 273

+: intestinal Ca absorption exceeds urinary excretion, difference deposited in growing bones -: intestinal absorption less than urinary excretion

Question 274

What are the 3 hormones involved in regulating Ca homeostasis?

Answer 274

Calcitonin Parathyroid hormone Calcitriol

Question 275

How does calcitonin work and what is its effect?

Answer 275

Gs-couple: inc. cAMP, inhibit osteoclast, less Ca resorption, more Ca incorporated into bone tissue Dec. Ca2+ Stimulated by inc. Ca2+ in plasma

Question 276

What is the function of PTH and what are its actions?

Answer 276

Inc. Ca Inc. bone resorption Inhib. renal P reabsorption in proximal tubule - excreted in urine Inc. renal Ca reabsorption in distal tubule Inc. intestinal Ca absorption indirectly by stimulating production of 1,25-dihydroxycholecalciferol

Question 277

What is the function of calcitriol?

Answer 277

PTH-like effect in bone | Mediated effects of PTH absorption of Ca and P by gut

Question 278

Where is calcitonin formed and secreted?

Answer 278

Parafollicular cells of thyroid

Question 279

Where is PTH formed and secreted?

Answer 279

Parathyroid gland

Question 280

How is the secretion of PTH regulated?

Answer 280

Negative feedback: secreted as serum Ca2+ falls

Question 281

How is VitD synthesised?

Answer 281

1. Skin cells convert 7-dehydrocholesterol to pro hormone cholecalciferol (B3) using sunlight 2. Liver then kidney convert pro hormone to active VitD3 (1,25-dihydroxycholecalciferol/dihydroxy-D3)

Question 282

What are the actions of VitD3?

Answer 282

1. Inc. intestinal Ca absorption 2. Inc. intestinal P absorption 3. Inc. renal reabsorption of Ca and P 4. Inc. resorption of bone

Question 283

What are osteomalacia/rickets?

Answer 283

Conditions caused by VitD deficiency leasing to poor bone mineralisation reducing bone mass thus making bones weak

Question 284

What are the 2 types of osteomalacia?

Answer 284

VitD-responsive | VitD-resistant

Question 285

Describe VitD responsive osteomalacia

Answer 285

Caused by deficiency in dietary intake of VitD precursors, inadequate sunlight exposure, malabsorption of Ca

Question 286

Describe the 2 forms of VitD-resistant osteomalacia

Answer 286

Pseudo-VitD: end-organ hyposensitivity | Hereditary VitD-resistant rickets: VitD receptor has poor affinity for its DNA due to mutation in the DNA binding domain

Question 287

What is osteoporosis and what are the 2 types?

Answer 287

Dec. in bone strength Primary: post menopause lose bone rapidly; calcitonin treatment as slows bone resorption Secondary: caused by corticosteroids, Cushing's syndrome, immobilisation, GI disease, alcohol, age senile due to dec. 1,25-dihydroxy-D3 secretion, dec. PTH levels

Question 288

Explain the evidence showing DNA is heredity genetic material

Answer 288

Virulent lysates contain inheritance materials that transformed harmless bacteria to virulent bacteria killing mouse Protein/RNA digestion (protease, ribonuclease) didn't destroy inheritance material - mouse died DNA digestion destroyed inheritance material preventing bacterial transformation thus mouse lived

Question 289

Describe the structure of DNA

Answer 289

Linear polymer of 4 nucleotides - adenine, thymine, guanine, cytosine - each made of base, phosphate group and deoxyribose sugar Nucleotides are linked by phosphodiester bonds and antiparallel strands held in double helix by H bonds between complementary base (AT, GC)

Question 290

What are the 3 DNA conformation?

Answer 290

B A Z | B most prominent but flexible nature of helix allows A Z conformations

Question 291

What is the Central Dogma Theory?

Answer 291

Specific DNA gene sequence gets transcribed into RNA, then translated into unique proteins

Question 292

Describe the process of DNA replication

Answer 292

1. Helicase unwinds double helix forming replication fork 2. Single-stranded DNA binding proteins stabilise SSDNA to prevent rebinding to double helix 3. RNA primase synthesises short fragments of RNA primer required for initiation of DNA synthesis by DNA polymerase 3 4. DNA polymerase 1, DNAse H replace RNA primers with DNA 5. DNA ligase joins Okazaki fragments (lagging strand) to create continuous newly synthesised DNA

Question 293

What are genes?

Answer 293

Basic unit of heredity in all living organisms

Question 294

What is the function of genes?

Answer 294

Encode for proteins essential for biological functions and structures Some produce non-coding RNA molecules that play role in protein biosynthesis and gene regulation

Question 295

What are the molecules that result from gene expression called?

Answer 295

Gene products

Question 296

How do cells read the genome?

Answer 296

DNA doesn't direct protein synthesis directly, use RNA intermediate used as template for protein synthesis Central Dogma of molecular biology

Question 297

Compare DNA and RNA

Answer 297

Sugar: DNA - deoxyribose; RNA - ribose Bases: ATGC; AUGC Structure: double stranded helix; single strand (siRNA is double)

Question 298

Describe the process of transcription

Answer 298

1. Small portion of DNA unwound 2. Only 1 of DNA strands acts as RNA template 3. RNA chain produced called transcript 4. RNA polymerase catalyses formation of phosphodiester bonds, moves stepwise along DNA, unwinding DNA helix to expose new region 5. Extended 1 nucleotide at a time in 5'-3' direction

Question 299

What is the significance of the direction of RNA polymerase?

Answer 299

Determines which DNA strand will be used as template as only work in 5'-3' direction

Question 300

Name and describe the role of the main transcription factors (TF)

Answer 300

TFIID + TBP: binds TATA-box in promoter region near imitation site TFIIA/B: binds TFIID/TBP forming complex for RNA polymerase to bind RNA polymerase: initiates transcription of RNA from DNA, requires ATP

Question 301

What are the 2 types of RNA?

Answer 301

Coding - 4% (mRNA) | Functional - 96%

Question 302

What are the 6 types of functional RNA?

Answer 302

rRNA: component of ribosomes where protein synthesis occurs tRNA: carry AAs to ribosomes Small nuclear: splice hnRNA to mRNA Small nucleolar: chemical modification of rRNA Micro + short interfering: regulate gene expression in eukaryotic cells

Question 303

What are the types of post-transcriptional RNA processing?

Answer 303

End-modification Splicing Cutting Chemical modification

Question 304

How is pre-mRNA converted to mRNA?

Answer 304

snRNPs bind to intron forming loop that pulls exons together | Intron loop is excised and exons spilled together forming mature mRNA

Question 305

What is mRNA translation?

Answer 305

Conversion of info. in mRNA into protein

Question 306

What are the rules of the genetic code?

Answer 306

Sequences of nucleotides in mRNA read in codons (groups of 3) each specifying an AA or stop signal

Question 307

Define what is meant by degenerate

Answer 307

Many codons are redundant as encode the same AA

Question 308

What is the binding of AAs dependent on?

Answer 308

tRNAs that recognise and bind both to codon (via complementary anticodon) and to AA

Question 309

How does the AA bind to tRNA?

Answer 309

Short, single-stranded 3' region of tRNA ribose binds to carboxyl end of AA forming ester bond

Question 310

What is the recognition and binding of correct AA dependent on?

Answer 310

Aminoacyl-tRNA synthetase | Covalently couples each AA to appropriate tRNA molecule

Question 311

How are ribosomes formed?

Answer 311

Ribosomal proteins synthesised in cytoplasm, transported back to nucleolus to bind with rRNA subunit and exported back to cytoplasm

Question 312

Describe the structure of ribosomes

Answer 312

1 small subunit, 1 large subunit Small: provides framework on which tRNA anticodons accurately matched to mRNA codons Large: catalyses formation of peptide bonds linking AAs

Question 313

What is the function of ribosomes?

Answer 313

Maintain the correct reading frame and ensure accuracy

Question 314

What are the 4 binding sites of ribosomes?

Answer 314

1. mRNA 2. Aminoacyl (A): tRNA with bound AA 3. Peptidyl (P): tRNA attached to growing peptide chain 4. Exit (E)

Question 315

Describe the process of protein synthesis

Answer 315

1. Ribosome subunit join near 5' end of mRNA 2. tRNA anticodon binds to complementary mRNA codon at A site bringing AA 3. Ribosome moves towards 3' end, at P site peptide bond forms between existing polypeptide and new AA 4. mRNA moves 1 codon along through small subunit, tRNA ejected at E site, A site free again

Question 316

What is the start codon of protein synthesis?

Answer 316

AUG which special tRNA binds to with methionine - distinct from usually methionine tRNA

Question 317

What is the importance of the start codon?

Answer 317

Dictates reading frame for whole protein Error can lead to frame shift mutation where reading frame is shifted causing all codons to be translated incorrectly forming non-functional protein

Question 318

What are the stop codons and how do they work?

Answer 318

UAA, UAG, UGA Signal binding of release factor Forces peptidyl transferase to bind water freeing carboxyl end of peptide that keeps peptide in ribosome Released into cytoplasm

Question 319

Define somatic and reproductive division

Answer 319

Somatic: cells of body reproduce themselves Reproductive: body produces gametes

Question 320

What is the function of somatic division?

Answer 320

Process by which body grows and replaces dead/damaged cells

Question 321

What is the feel cycle?

Answer 321

Orderly sequence of events in which the cell: duplicates its contents, divides

Question 322

Why must contents must be duplicated for the CC?

Answer 322

So genes can be passed onto next generation

Question 323

What are the 2 major phases of the CC?

Answer 323

Interphase: not diving | Mitotic phase: diving

Question 324

What is interphase?

Answer 324

State of high metabolic activity during which cell does much frowning and replicates DNA and organelles/proteins

Question 325

What are the 3 stages of interphase and state what happens during them

Answer 325

G1: replicates organelles and cytosol S: DNA replication G2: enlarges, synthesises enzymes and proteins for mitosis

Question 326

What is the G0 phase?

Answer 326

Phase most cells are in | If exit cell cycle enter G0, usually cannot re-enter

Question 327

What are the 2 stages of the mitotic phase?

Answer 327

Mitosis: nuclear division Cytokinesis: cell division

Question 328

What are the 4 phases of mitosis and what happens during each?

Answer 328

Prophase: chromatin condense to paired chromatids, nucleolus and nuclear membrane disappear, centrioles move to opp. poles Metaphase: chromatids line up on metaphase plate Anaphase: identical sets of chromosomes move to opp. poles Telophase: nuclear envelope and nucleoli re-appear, chromosomes resume chromatin form

Question 329

When does cytokinesis occur and what happens?

Answer 329

In late anaphase Contractile ring forms cleavage furrow around centre of cell Cytoplasm divided into 2 equal portions

Question 330

What are cyclins and Cdks?

Answer 330

Cyclins are regulatory proteins that activate Cdks | Rb tumour suppressor gene is the major target of Cdks which they phosphorylate at multiple points throughout CC

Question 331

What is meant by G1 restriction point being the 'point of no return'?

Answer 331

Once cell proceeds through point it will complete CC including mitosis and cytokinesis

Question 332

How can inhibitors block the CC?

Answer 332

Inhibitors of Cdk4 (INK4 protein) can prevent phosphorylation of Rb

Question 333

Define hypertrophy and give examples of chronic hypertrophy

Answer 333

Increase in size of cell without division Cirrhosis of liver: hepatocytes become swollen causing narrowing of sinusoids Heart conditions: cardiac myocytes hypertrophy in response to excessive workload

Question 334

What is atrophy?

Answer 334

Decrease in size/number of cells and subsequent decrease in size of tissue/organ Cachexia seen in HIV and cancers

Question 335

Define hyperplasia and give example of chronic

Answer 335

Increase in no of cells due to inc. in cell division Psoriasis in skin Make prostate may lead to benign or malignant tumour

Question 336

What is a cancer?

Answer 336

Cells that divide without control | Usually associated with loss of tissue differentiation and function (anaplasia)

Question 337

What are tumours?

Answer 337

Swelling or lesion formed by abnormal cells | May be cancerous (malignant) and usually spread to other organs (metastasis)

Question 338

How does epidermal growth factor regulate cyclin D1 production?

Answer 338

1. EGF binds receptor, activates G protein 2. kinase cascade will phosphorylate AP1 transcription factor through jun subunit 3. TF binds promoter region of cyclin D1 causing transcription of cyclin D1

Question 339

Define glycolysis

Answer 339

Breakdown of glucose to 2 pyruvate and ATP molecules

Question 340

Define glycogenesis

Answer 340

Assembly of glycogen from excess glucose | Requires ATP, initiated by insulin

Question 341

Define glycogenolysis

Answer 341

Breakdown of glycogen to glucose | Regulated by glucagon

Question 342

Define gluconeogenesis

Answer 342

Synthesis of glucose from metabolites (lactate, pyruvate, glycerol, alanine)

Question 343

What are Islets of Langerhans?

Answer 343

Highly vascularised endocrine glands in the pancreas | High vascularisation allows hormones ready access to circulation

Question 344

What are the 4 secretory cells of the Islets?

Answer 344

a: glucagon B: insulin Delta Digamma

Question 345

What are the functions of insulin?

Answer 345

Regulate blood glucose: signals liver, muscles, adipose to take up glucose; aides cells taking up for energy Signal storage of Glc as Gly when in excess

Question 346

Describe the synthesis of insulin

Answer 346

1. Leader sequence cleaved leaving proinsulin made of A,B,C domains 2. Proteases cleave proinsulin in 2 places releasing peptide C and mature insulin (A,B joined by S-S bond) 3. Packaged into secretory granules containing equimolar amounts of insulin and peptide C 4. Released into extracellular space during secretion

Question 347

Describe the 7 steps of insulin release

Answer 347

1. Glc enters via GLUT2 2. Inc. influx inc. Glc metabolism, inc. [ATP]i 3. Inc. [ATP]i inhib. KATP channel 4. Closed KATP causes depolarisation 5. Depolarisation activates VGCa2+C in PM 6. Influx of Ca2+, inc. Ca2+ induces Ca2+-induced Ca2+ release 7. Ca2+ leads to exocytosis, releasing secretory granules

Question 348

What are the 3 chemical controls of insulin release?

Answer 348

AAs: stim. (inc. uptake and protein synthesis) Keto acids: stim. (inc. uptake to prevent lipid and protein utilisation) Glucose: stim. (feedback loop)

Question 349

What hormones are B cells sensitive to?

Answer 349

Glucagon - inhib. | Somatostatin - inhib

Question 350

Describe the neuronal control of insulin release

Answer 350

PSNS: ACh stim SNS: NA inhib

Question 351

Describe the stim. of Glc disposal postprandial

Answer 351

Insulin binds receptor Insulin signalling pathway activates: effects on protein metabolism, effects on growth, effects on lipid metabolism and translocation of GLUT4 containing vesicles to PM Inc. Glc uptake

Question 352

Describe the inhib. of Glc production postprandial

Answer 352

Insulin blocks Glc production via glycogenolysis and gluconeogenesis PEPCK (inhib gluconeogenesis) and glycogen phosphorylase both targeted Can be acute (dephosphorylation of phosphorylase) or long-term (suppression of PEPCK gene expression)

Question 353

Describe the effects of insulin on adipocyte lipid metabolism

Answer 353

Stim: lipoprotein lipase (LPL), FA uptake, triglyceride esterification Inhib: adipose TAG lipolysis preventing release of FA and glycerol

Question 354

What are the functions of glucagon?

Answer 354

Stim. glycogenolysis Stim. gluconeogenesis Stim. lipolysis

Question 355

Describe how glucagon is regulated

Answer 355

Inc. Glc inhib. release AAs stim. release Stress: AD acts on B receptors on a cells stim. release Insulin inhib. glucagon release

Question 356

How does glucagon stimulate hepatic Glc production?

Answer 356

Stim. gluconeogenesis and glycogenolysis

Question 357

Describe the effects on insulin and glucagon on hepatic lipid homeostasis during fasting

Answer 357

Insulin: suppresses lipin-1 red. VLDL production, carnitine palmitoyltransferase 1 (CPT1) thus inhib. ketogenesis Glucagon: opposite effects thus inc. VLDL production and stim. ketogenesis

Question 358

What is the structure of glycogen?

Answer 358

Polymer of glucose residues linked a(1,4) between molecules and a(1,6) at branching points

Question 359

What does glycogen phosphorylase catalyse?

Answer 359

Gly(n residues) + Pi -> gly(n-1 residues) + glc-1P Catalyses phosphorolytic cleavage of a(1,4) glycosidic linkages Glc-1P released as product

Question 360

What is the prosthetic group for GP?

Answer 360

``` Pyridoxal phosphate (PLP) Phosphate used to break bond ```

Question 361

What is the function of phosphoglucomutase?

Answer 361

Catalyse glc-1P -> glc-6P Glc-6P either enter glycolysis or dephosphorylated for release to blood Free energy = 0, reaction dependent on conc.

Question 362

Explain how glycogen debranching enzyme work

Answer 362

When 4 residues left glycogen phosphorylase stops a(1,4) transglycosylase transfers 3 residues into linear chain a(1,6) glucosidase removes remaining glc

Question 363

Describe liver glycogenolysis and its importance

Answer 363

Glc-6Pase coverts glc-6P to glc Liver gly converted to glc due to presence of glc-6Pase Substitutes for gut during initial stage of starvation as liver glycogen results in direct release of glucose

Question 364

Describe skeletal muscle glycogenolysis

Answer 364

Lack glc-6Pase so glc-6P enters glycolysis Glycogenolysis generates ATP for contraction Lactate generated transported in blood to liver, precursor for gluconeogenesis

Question 365

What are the 2 steps of glycogen synthesis?

Answer 365

Formation of UDP-glc | Glycogen synthesis

Question 366

Describe the formation of UDP-glc

Answer 366

From glc-1P Glc-1P + UTP -> UDP-glc + PPi PPi + H20 -> 2Pi Overall: Glc-1P + UTP -> UDO-glc + 2Pi Spontaneous hydrolysis of P bond in PPi drives reaction Cleavage of PPi only energy cost in glycogenesis

Question 367

Describe glycogen synthesis

Answer 367

Glycogen synthase catalyses Gly(n residues) + UDP-glc -> gly(n+1 residue) + UDP Catalyses transfer of glc to OH C4 of terminal residue of gly chain forming a(1,4) Branching enzyme transfers segment from end of gly to OH C6 of glc residue of gly forming a(1,6) 4 residues from existing branch

Question 368

How is glycogenesis regulated?

Answer 368

``` Modification 1 (phosphorylase) Phosphorylase b (less active) phosphorylated to phosphorylase a (more active) which inhib. glycogenesis Dephosphorylated by phosphoprotein phosphatase-1 ``` ``` Modification 2 (glycogen synthase) GS a (active) phosphorylated to GS b (inactive) inhib. glycogenesis Dephosphorylated by phosphoprotein phosphatase-1 ```

Question 369

Explain how cAMP controls glycogenesis

Answer 369

Glucagon and NA inc. cAMP levels, activates PKA PKA phosphorylates GS to inactive form - inhib. glycogenesis PKA phosphorylates phosphorylase kinase (active) which phosphorylates GP (active) inhib. glycogenesis (enhance glycogenolysis) Insulin inhib. cAMP suppressing glycogenolysis

Question 370

Describe insulin control of glycogenesis

Answer 370

Insulin activates GS phosphatase which dephosphorylates GS (active) Glycogenesis occurs GS kinase 3 and cAMP phosphorylate (inactive) GS, insulin suppresses GSK3, cAMP enhancing glycogenesis

Question 371

What is gluconeogenesis?

Answer 371

Synthesis of glc from non-carb C substrates - lactate, pyruvate, glycerol, glycogenic AAs

Question 372

What is the importance of gluconeogenesis?

Answer 372

During fasting liver glycogen is depleted Gluconeogenesis is source of glucose during this Requires energy and C source

Question 373

What are the 2 important enzymes of gluconeogenesis and where are they found?

Answer 373

Pyruvate carboxylate - mitochondria | Glc-6Pase - ER

Question 374

What is the role of pyruvate carboxylase?

Answer 374

Catalyse pyruvate to oxaloacetate Allosterically activated by acetyl-CoA [oxaloacetate] limiting factor for Krebs cycle In active gluconeogenesis oxaloacetate diverted to form glc, inc. [acetyl-CoA] activates pyruvate carboxylase

Question 375

Outline the steps of gluconeogenesis

Answer 375

Opposite of glycolysis with 4 differences 1. PC: pyruvate -> oxaloacetate 2. PEPCK: oxaloacetate -> phosphoenolpyruvate 3. Enolase: PEP -> 2-phosphoglycerate 4. Phosphoglycerate mutase: 2-phosphoglycerate -> 3-phosphoglycerate 5. Phosphoglycerate kinase: 3-phosphoglycerate -> 1,3-bisphosphoglycerate 6. Glyceraldehyde-3P Dehydrogenase: 1,3-bisphosphoglycerate -> glyceraldehyde-3P 7. Triosphosphate isomerase: glyceraldehyde-3P dihydroxyacetate-P 8. Aldolase: glyceraldehyde-3P + dihydroxyacetate-P -> fructose-1,6-bisP 9. Fructose-1,6-bisPase: fructose-1,6-bisP -> fructose-6P 10. Phosphoglucose isomerase: fructose-6P -> glucose-6P 11. Glc-6Pase: glucose-6P -> glucose

Question 376

How is the pyruvate kinase reaction of glycolysis reversed in gluconeogenesis?

Answer 376

Using pyruvate carboxylase, malate dehydrogenase, PEP carboxykinase Pyruvate enters mitochondria and converted to oxaloacetate by PC MDH catalyses oxaloacetate to malate Malate exits mitochondria converted to oxaloacetate (enters gluconeogenesis) Oxaloacetate converted to PEP by PEPCK and continues gluconeogenesis

Question 377

How is gluconeogenesis regulated?

Answer 377

Glc-6Pase: [Glc-6P] Fructose-1,6-bisPase: AMP, fructose-1,6-bishop (inhib) PC: acetyl-CoA (enhance)

Question 378

Describe the effect of glucagon-cAMP cascade in the liver

Answer 378

Gluconeogenesis stim Glycolysis inhib Glycogenesis inhib Glycogenolysis stim Free glc released to blood

Question 379

Explain how glucose/glycogen can be a C source for gluconeogenesis

Answer 379

Glycolysis forms lactate which is converted to pyruvate by lactate dehydrogenase

Question 380

Explain how proteins can be a C source for gluconeogenesis

Answer 380

Proteolysis forms AAs which are broken down to pyruvate | All AAs except lysine and leucine can supply C

Question 381

Explain how triglyceride can be a C and ATP source

Answer 381

Lipolysis produces glycerol and FAs Glycerol enters hepatic gluconeogenesis FAs oxidised releasing ATP, acetyl-CoA, NADH Acetyl-CoA and NADH inhib. pyruvate dehydrogenase enzyme (prevents loss of CO2, more pyruvate for gluconeogenesis) Acetyl-CoA enhances PC (more oxaloacetate)

Question 382

Outline the 8 steps of the TCA cycle Can I Keep Selling Sex For Money Officer? CAIK Sounds So Fucking Mint

Answer 382

``` Citrate Isocitrate a-ketoglutarate Succinyl-CoA Succinate Fumarate Malate Oxaloacetate ``` ``` Citrate synthase Aconitase Isocitrate dehydrogenase a-ketoglutarate dehydrogenase Succinyl-CoA synthase Succinate dehydrogenase Fumarase Malate dehydrogenase ```

Question 383

What step of TCA is substrate level phosphorylation?

Answer 383

Succinyl-CoA synthase: Succinyl-CoA succinate | GDP -> GTP

Question 384

What are the products of TCA per glucose?

Answer 384

6 NADH2 2 FADH 2 GTP

Question 385

What 3 subunits make pyruvate dehydrogenase enzyme?

Answer 385

1. Pyruvate carboxylase 2. Lipoamide reductase transacetylase 3. Dihydrolipoyl dehydrogenase

Question 386

What are the 3 conditions and fates of acetyl-CoA?

Answer 386

1. Presence of carbs and energy used: metabolised to CO2, NADH, FADH2, GTP - all eventually ATP 2. No energy use: made into fat 3. Energy, no carbs: ketone bodies

Question 387

What 2 steps of TCA are endergonic?

Answer 387

Aconitase: citrate isocitrate | Malate dehydrogenase: malate oxaloacetate

Question 388

What are the 2 regulatory steps in TCA?

Answer 388

Isocitrate dehydrogenase | a-ketoglutarate dehydrogenase

Question 389

What factors stimulate and inhibit the 2 regulatory dehydrogenases?

Answer 389

1. Inc. [ATP/NADH] inhibits | 2. Ca2+ stimulates

Question 390

In the fed state what is the biosynthetic role of TCA?

Answer 390

Excess glucose converted to acetyl-CoA then citrate which is exported from mitochondria ATP and citrate lyase convert citrate to acetyl-CoA and oxaloacetate Acetyl-CoA then enters lipogenic acid and cholesterol synthesis pathways to forms FAs and cholesterol

Question 391

What is the biosynthetic role of TCA in the fasted state?

Answer 391

AAs that can be converted to oxaloacetate yield net glucose synthesis FAs can't be converted as C atoms from acetyl-CoA lost as CO2 Acetyl-CoA can't be converted to pyruvate as reaction irreversible

Question 392

How does FA oxidation block glucose oxidation?

Answer 392

Acetyl-CoA and NADH (produced by FAO) are inhibitors of PDC which converts pyruvate to acetyl-CoA Acetyl-CoA and NADH stimulate PDC kinase to phosphorylate PDC to inactive form

Question 393

What happens to citrate when glucose is ample?

Answer 393

Exported from mitochondria and converted to acetyl-CoA then malonyl-CoA (FA synthesis precursor) Rise in malonyl-CoA inhibits COR-1 and suppresses FAO

Question 394

How do hypoxic events upregulate glycolysis?

Answer 394

Hypoxia-inducible factor (HIF1) transcription factor is stabilised, bind to hypoxia responsive elements in promoter regions including glycolytic enzymes

Question 395

How does chronic HIF action low mitochondrial respiration?

Answer 395

HIF1 downregulates mitochondrial respiration by promoting mitochondria autophagy and suppressing mitochondrial biogenesis May be adaptive mechanism to prevent oxidative stress by restricting production of reactive oxygen species

Question 396

Defined glucogenic and ketogenic

Answer 396

Glucogenic: glucose can be formed from C skeleton Ketogenic: AAs degraded to acetyl-CoA

Question 397

What are the 10 essential AAs? | PVT TIM HALL

Answer 397

Phenylalanine Valine Tryptophan Threonine Isoleucine Methionine Histidine Arginine Leucine Lysine

Question 398

Give an overview of AA metabolism

Answer 398

Ingested protein, biosynthesis and degraded proteins produce AAs AAs produce proteins, purines, pyrimidines, porphyrins Degraded to C skeleton and N N excreted in urea C skeletons to ketogenic/glucogenic products

Question 399

What are the 3 steps to AA degradation?

Answer 399

NH2 group removed Detoxification of amino group Metabolism of C skeleton

Question 400

Outline the urea cycle

Answer 400

Ammonia converted to carbamoyl phosphate which reacts with ornithine to form citruline Citruline converted to arginino-succinate by argininosuccinate synthase and broken down to arginine by argininosuccinate lyase Arginine converted to ornithine releasing urea by arginase

Question 401

What are the general effects of insulin?

Answer 401

``` Start Glucose uptake in muscle, adipose Glycolysis Glycogen synthesis Protein synthesis Uptake of ions ``` ``` Stop Gluconeogenesis Glycogenolysis Lipolysis Ketogenesis Proteolysis ```

Question 402

Compare regulation of blood glucose in fed and fasting states

Answer 402

Fed: insulin secreted by beta cells, stimulates synthesis of metabolic fuel store, lower glucose level Fasting: glucagon secrete by alpha cells, stimulates mobilisation of metabolic fuel store, raises glucose

Question 403

Describe diabetes mellitus

Answer 403

Common endocrine disorder characterised by hyperglycaemia due to defects in insulin production, an absolute or relative lack of insulin or cell resistance to insulin

Question 404

What are the 2 main types of diabetes?

Answer 404

1. Insulin dependent DM/Type 1: IDDM | 2. Non-insulin dependent DM/Type 2: NIDDM

Question 405

What is secondary diabetes mellitus?

Answer 405

Diabetes that arises as consequence of another condition

Question 406

How may secondary diabetes arise?

Answer 406

Pancreatic disease Endocrine disease Drug therapy Insulin receptor abnormality

Question 407

Describe T1 diabetes

Answer 407

Can occur at any age, most common in young Autoimmune destruction of beta cells cause absolute lack of insulin Viral infections may be possible precipitating factor Can be predicted by presence of Islet cell antibody presence in serum

Question 408

Describe T2 diabetes

Answer 408

Occur any age, most common 40-80yo Resistance of tissues to action of insulin, insulin levels normal to high Commonly associated w/ obesity

Question 409

What is type 3 diabetes?

Answer 409

Gestational diabetes | Occurs in 3-10% pregnancies

Question 410

Describe T3 diabetes

Answer 410

Non-diabetics exhibit high blood glucose during pregnancy | Presence of human placental lactogen interferes w/ susceptible insulin receptors causing them to not function properly

Question 411

What are the risks associated w/ T3 diabetes?

Answer 411

Being large for gestational age, low blood sugar, jaundice (in child) Unmanaged: develop T2, higher incidence of pre-eclampsia, C-section Children: obesity and T2 diabetes

Question 412

What predisposing factors are associated w/ T1 diabetes?

Answer 412

Interplay of 3 leading to selective destruction of beta cells 1. Genetic 2. Environmental: diet, toxins, viral 3. Autoimmune: presence of islet antibodies

Question 413

What predisposing factors are associated w/ T2 diabetes?

Answer 413

Complex genetic interactions modified by environmental Genetic: familia aggregation, susceptibility genes Obesity, physical inactivity, stress Adipocyte-derived hormones and cytokines, metabolically active hormones may affect insulin sensitivity

Question 414

What 6 symptoms are associated w/ hyperglycaemia?

Answer 414

1. Polyuria 2. Polydipsia 3. Lassitude 4. Weight loss 5. Polyphagia 6. Blurred vision

Question 415

What complications are associated w/ diabetes?

Answer 415

Leading cause of death and early disability Inc. risk of cardiac, cerebral, peripheral vascular disease Altered hand/foot sensation Inc. risk of periodontal disease

Question 416

What are the acute compilations of diabetes?

Answer 416

1. Hyperglycaemia 2. Diabetic ketoacidosis 3. Hyperglycaemic hyperosmolar non-ketotic coma

Question 417

What are 5 chronic complications of diabetes?

Answer 417

1. Microangiopathy: small blood vessels 2. Macroangiopathy: large blood vessels 3. Neuropathy: 4. Retinopathy: blindness 5. Nephropathy: kidney failure

Question 418

What are the 3 main tests for diabetes?

Answer 418

1. Random blood sample 2. Fasting blood sample 3. Oral glucose tolerance test

Question 419

For random blood glucose, at what level would diabetes be diagnosed?

Answer 419

>/= 11.1 mmol/L

Question 420

For fasting sample what levels of glucose are deemed non-diabetic, impaired fasting glycemic and diabetic?

Answer 420

Non: <6.0 Impaired: 6.1-6.9 Diabetic: >7.0

Question 421

For oral glucose test what glucose levels for fasting and 2 hours later are deemed impaired glucose tolerance and diabetic?

Answer 421

Fasting: impaired <7.0, diabetic >/=7.0 | 2 hour: impaired 7.8-11.0, diabetic >/=11.1

Question 422

Why is HbA1c assessment preferred in monitoring diabetes?

Answer 422

More reliable and accurate assessment of long term control as represent long term blood glucose level during lifetime of protein

Question 423

What is glycation?

Answer 423

Irreversible, enzymatic attachment of glucose to proteins

Question 424

What is HbA1c count?

Answer 424

Measurement of average blood glucose level during preceding 60-90 days before testing Measured as % of total haemoglobin conc.

Question 425

What is a good HbA1c count?

Answer 425

7%

Question 426

What are the 4 predisposing factors of diabetic ketoacidosis?

Answer 426

All in/direct result of lack of insulin 1. Infection 2. Myocardial infarction 3. Trauma 4. Omission of insulin

Question 427

What happens in the absence of insulin?

Answer 427

Muscle and adipose breakdown triglycerides to produce FAs as alternative energy source Inc. lipolysis leads to overproduction of FAs, converted into ketones can cause ketonaemia, metabolic acidosis, ketonuria

Question 428

What happens as glucose transport into tissues decreases?

Answer 428

Hyperglycaemia leading to glycosuria resulting in osmotic diuresis causing loss of water and electrolytes Will result in severe dehydration, cause pre-renal uraemia and may lead to hypovolaemic shock

Question 429

What is the clinical relevance of diabetes?

Answer 429

How will treatment subsequently affect eating: will it lead to hypoglycaemia? Collapsing Hyperglycaemia: loss of consciousness but long process from onset of symptoms to loss of consciousness Hypoglycaemia: may be evident within mins, rapidly lead to loss of consciousness or develop gradually and lead to profession of alteration in consciousness

Question 430

What is a counter regulatory hormone?

Answer 430

A hormone that opposes affect of another hormone i.e. an antagonist

Question 431

What are the 4 main insulin CRHs and what do they respond to?

Answer 431

1. Glucagon 2. AD 3. Cortisol 4. Growth hormone Respond to hypoglycaemia

Question 432

What are the 3 methods for non-diabetic control of hypoglycaemia?

Answer 432

1. Pancreas reduce insulin secretion 2. Alpha cells secrete glucagon, liver release more glucose 3. Adrenal glands secrete AD; liver and kidneys produce more glucose prevents tissues using glucose from bloodstream red. insulin secretion

Question 433

What happens if glucagon and AD fail to return glucose levels to normal?

Answer 433

hGH and cortisol will raise glucose

Question 434

What is the function of hGH?

Answer 434

Childhood: regulate growth rate Adult: maintain muscle and bone mass, tissue repair and healing Secreted by somatotrophs Main function is to stimulation production of insulin-like growth factor by cells in liver, skeletal muscle, cartilage, bone

Question 435

What is the function of ILGF?

Answer 435

Stimulate release of glucose into blood by liver

Question 436

What do hypoglycaemia and hyperglycaemia stimulate the hypothalamus to release?

Answer 436

Hypo: GH-releasing hormone Hyper: GH-inhibiting hormone

Question 437

What are the sections of the adrenal glands?

Answer 437

Cortex: outer 80% Medulla: inner 20%

Question 438

Describe the adrenal cortex

Answer 438

Many LDL receptors Enable cholesterol uptake for steroid hormone synthesis Secrete: glucocorticoids (cortisol), mineralcorticoids (aldosterone), androgens

Question 439

Describe the adrenal medulla

Answer 439

Secrete: catecholamine hormones (NA, AD) and dopamine

Question 440

Describe cortisol

Answer 440

Secreted in response to ACTH from pituitary | -ve feedback loop

Question 441

Describe aldosterone

Answer 441

Stimulated by inc. K+ plasma | Regulates electrolyte balance

Question 442

Describe androgens

Answer 442

Steroid hormones that have masculinising effects

Question 443

What are the 3 hormone systems of the adrenal glands?

Answer 443

1. Glucocorticoids (cortisol) 2. Mineralcorticoids (aldosterone) 3. Androgens

Question 444

What is adrenocorticotrophic hormone?

Answer 444

Regulatory hormone secreted by corticotrophs in ant. pituitary Controls production and secretion of cortisol/glucocorticoids by adrenal cortex Stimulated by CRH from hypothalamus, stress stimuli (trauma, blood glucose) and interleukin-1 from macrophages

Question 445

Describe the action of glucocorticoids/cortisol

Answer 445

Binds to cytosolic receptor and translocated to nucleus upon activation Regulates BP and suppresses inflammation Enhances: gluconeogenesis, adipose tissue lipolysis, muscle proteolysis Inhib: glucose utilisation

Question 446

Describe catecholamine action

Answer 446

Release in response to stress Characterised by inc. O2 consumption and hypermetabolism AD stim: glycogenolysis in liver and muscle; gluconeogenesis in liver Stim: adipose alternative fuel cells to glucose Inc. HR

Question 447

Describe hypofunction of the adrenal glands

Answer 447

Adrenal insufficiency; rare, potentially fatal Signs: lethargy, anorexia, low BP, hypoglycaemia, hyperpigmentation Life threatening Na depletion and possible K retention due to aldosterone deficiency causing low BP Therapy: Na maintenance, hormone replacement

Question 448

What is hyperfunction of adrenal cortex?

Answer 448

Overproduction of cortisol, androgens and aldosterone | Prolonged, excessive exposure can lead to Cushing's syndrome

Question 449

What is Cushing's syndrome?

Answer 449

When ACTH levels don't respond to -ve feedback from high cortisol levels Characterised by remodelling of adipose tissue: deposition on face and trunk, loss from limbs Wasting of skeletal muscle, osteoporosis, slow healing, thinning of skin Excess cortisol may lead to diabetes and hypertension

Question 450

What are tetraiodothryonine and triiodothyronine?

Answer 450

Thyroid hormones 4 and 3 Are thryonines w/ 3/4 iodine atoms Regulated by controlling conversion of 4 to 3 (active from) in target tissues (liver, kidney)

Question 451

Described the mechanism of thyrothropin releasing hormone and thyroid stimulating hormone

Answer 451

TRH controls TSH release TSH stimulates production and secretion of T3 and 4 by thyroid T3and4 control release of TRH

Question 452

What are the 9 general metabolic effects of thyroid hormones?

Answer 452

Inc: basal metabolic rate, body temp, glucose and FA use for ATP synthesis, glucose uptake, lipid and protein turnover Stim: protein synthesis, lipolysis, synthesis of Na/K ATPase Effect on gene expression: slow, long lasting Regulate development and growth of nervous tissue and bones

Question 453

What are the 8 clinical features of hypothyroidism (myxoedema)?

Answer 453

1. Lethargy, tiredness 2. Weight gain 3. Apathy 4. Slow pulse 5. Cold intolerance 6. Constipation 7. Myxoedema 8. Elevated serum TSH

Question 454

What are the 7 clinical features of hyperthyroidism (thyrotoxicosis)?

Answer 454

1. Hyperactivity, insomnia 2. Weight gain 3. Diarrhoea 4. Palpitation 5. Heat intolerance 6. Suppressed TSH, elevated T4 7. Agitation

Question 455

What is body mass index?

Answer 455

Universally accepted classification of obesity | Person's weight (kg) in relation to height (m)

Question 456

What are the BMIs for normal, over weight and the 3 classes of obesity?

Answer 456

``` Normal: 18.5-24.9 Overweight: 25.0-29.9 Class I: 30.0-34.9 Class II: 35.0-39.9 Class III: >40.0 ```

Question 457

Describe the co-morbidity risk changes as weight inc.

Answer 457

``` Normal: no inc. Overweight: inc. Class I: moderate inc. Class II: severe inc. Class III: v severe inc. ```

Question 458

Discuss the advantages of BMI

Answer 458

Low-cost, easy to use Commonly used to determine healthy weight, can compare weight to GP Correlates well w/ amount body fat measured by complex techniques Predicts dangers; as BMI inc. risk inc. Useful screening tool to use @ popn. level, as universally used lots of data from many popns.

Question 459

What is the disadvantage of BMI?

Answer 459

Fails to distinguish between fat and muscle

Question 460

What is obesity?

Answer 460

Excessive accumulation of fat

Question 461

What 2 methods can be used to assess obesity?

Answer 461

1. Waist circumference | 2. Waist-hip ratio

Question 462

Describe waist circumference

Answer 462

Taken at level of iliac crest Men: >40" health risk Women: >35" health risk

Question 463

Describe waist-hip ratio

Answer 463

Waist circumference @ level of L3 over hip circumference @ largest gluteal region Men: >1.0 Women: >0.85

Question 464

Describe the changes in epidemiology and prevalence of obesity

Answer 464

WHO says it is now an epidemic | In last 10yrs inc. by 10-40% in most European countries

Question 465

Describe prevalence of obesity in Britain

Answer 465

Now has highest obesity rate of all Western European counties: 50% overweight, 20% obese >1.1billion adults overweight, 312mil clinically obese 10% children overweight/obese, 17.6mil <5 overweight

Question 466

What are the 4 main factors for cause of obesity?

Answer 466

1. Genes 2. Socio-economic: diet and lifestyle 3. Cultural 4. Psychological and medical

Question 467

What is the evidence for genes playing a role in obesity?

Answer 467

Adults who were adopted as children have weight closer to biological parents Monozygotic twins show much stronger correlation in weight than dizygotic twins

Question 468

Describe the socio-economic factors in obesity

Answer 468

Diet Inc. energy dense foods: animal fats Dec. complex carbs: fibres, coarse grains Inc. alcohol, salt ``` Lifestyle Affluent life w/ less physical activity Car: drive instead of walk TV/games: long time sitting/watching Energy/time saving devices: red. manual labour in home ```

Question 469

How do cultural factors play a role in obesity?

Answer 469

In some countries big is attractive and sign of health and prosperity

Question 470

Describe the psychological and medical factors contributing obesity

Answer 470

Psychological: eat in response to -ve emotions; sadness, anger, boredom Conditions: depression, hypothyroidism, chromosomal anomalies Drugs: corticosteroids, antidepressants, antipsychotics, B-blockers, oral contraceptive, oral hypoglycaemic agents, insulin, antihistamines

Question 471

What are the 9 possible effects of obesity?

Answer 471

1. Hypertension 2. Stroke 3. T2 diabetes 4. Cancer: endometrium, breast, prostate, colon 5. CV mortality 6. Respiratory diseases, sleep-apnea 7. Osteoarthritis 8. Gallbladder disease 9. Metabolic syndrome

Question 472

What are the 2 main types of obesity?

Answer 472

1. Intra-abdominal/visceral | 2. Lower body/external

Question 473

What are the 6 main CV diseases associated with obesity?

Answer 473

1. Hypertension 2. Atherosclerosis 3. L ventricle hypertrophy 4. Cardiac necrosis 5. Cardiac arrhythmias 6. Heart attack

Question 474

How does obesity cause hypertension?

Answer 474

Inc. body mass associated w/: Inc. blood vol. and viscosity Inc. angiotensinogen release from adipocytes Inc. cholesterol and BP

Question 475

What effect does atherosclerosis have on the heart?

Answer 475

Inc. workload

Question 476

What affect does inc. workload have on the heart?

Answer 476

L ventricle hypertrophy

Question 477

What happens when heart workload continues to inc.?

Answer 477

Coronary arteries unable to sustain heart Ischaemia: lack of blood Unable to manifest during high demand Heart loses elasticity: unable to relax completely, dec. filling, dec. blood pumped around body

Question 478

What is congestive heart failure?

Answer 478

Inability of heart to contract properly

Question 479

Explain how obesity can lead to T2 diabetes

Answer 479

Insulin secreted in response to intake of food Prolonged periods of food intake causes constant production of insulin Cellular insulin receptors are down regulated leading to insulin resistance High levels of FAs and glucose in blood Depletion of glucose reserves as glucose not transported Person feels hungry and eats more

Question 480

What are the 5 methods of treatment of obesity?

Answer 480

1. Dietary modifications 2. Behavioural modifications 3. Physical activity 4. Pharmacological 5. Surgery

Question 481

Describe dietary modifications for the treatment of obesity

Answer 481

Nutritionally balanced, low calorie Inc.: fruit, veg, whole grains, nuts Dec.: fatty, sugary foods

Question 482

Describe some behavioural modifications to treat obesity

Answer 482

Keep food diary: time, place, activity, emotions; find link to period of eating/inactivity Help to avoid eating when in feet, watching TV, playing games etc Encouraged to eat home cooked meals and walk rather than use car

Question 483

When should pharmacological treatment of obesity be considered?

Answer 483

18-75yrs: BMI >30 BMI >27 w/ pre-existing risk factor: hypertension, diabetes, obstructive sleep apnoea, cardiac disease BMI >30 and 3 months care not red. weight

Question 484

What 2 drugs are licensed to be used in treatment of obesity?

Answer 484

1. Orlistat | 2. Sibutramine

Question 485

Describe orlistat

Answer 485

Prevents fat digestion and absorption by binding to GI lipase Useful for those w/ high fat diet

Question 486

Describe sibutramine

Answer 486

Red. appetite and inc. thermogenesis | Useful for those who can't control appetite

Question 487

What must be taken into consideration when a patient is on pharmacological treatments of obesity?

Answer 487

Shouldn't be sole therapy Must be strictly and regularly monitored: discontinued if weight loss <5% after 12ws or weight gain recurs Shouldn't be on longer than year, never more than 2 years

Question 488

Describe surgical treatment of obesity

Answer 488

Only in severe cases: BMI >40 2 accepted procedures: gastroplasty, gastric bypass Both red. stomach to small pouch to limit amount of food that can be consumed

Question 489

Describe vitamins

Answer 489

Class of organic compounds categorised as essential nutrient Required for normal function, growth and maintenance Essential for several enzymatic process in human metabolism Are cofactors: don't do anything themselves

Question 490

What are the 2 classes of vitamins?

Answer 490

1. Fat soluble: A D E K | 2. Water soluble: B complexes, C

Question 491

Describe water soluble vitamins

Answer 491

``` Source: fruits, vegs, grains, meat Absorption: directly into bloodstream Storage: circulating freely, not stored in body Excretion: excess in urine Toxicity: rare, possible w/ supplements ```

Question 492

Describe fat soluble vitamins

Answer 492

``` Source: fats and oils in food Absorption: w/ lipids through lymphatic system Storage: in fat and liver Excretion: not easily excreted Toxicity: easily reached ```

Question 493

Describe the sources, RDA and toxicity of vit A

Answer 493

Source: meat, liver, diary products Retinol - active form yellow, red, green fruits and vegetables; Carotene - precursor RDA men: 0.7mg/day; women: 0.6mg/day Toxicity: >1.5mg/day Painful joint, anorexia and/or vomiting, liver damage, fatigue, loss of hair

Question 494

What are the 4 functions of vit A?

Answer 494

1. Promote vision: retinal needed in rhodopsin 2. Protein synthesis and cell differentiation 3. Reproduction and growth 4. Bone growth remodelling

Question 495

What are the 5 ocular and 3 extra-ocular effects of vit A deficiency?

Answer 495

Ocular 1. Night blindness 2. Conjunctival xerosis 3. Bitot's spots 4. Corneal xerosis 5. Keratomalacia Extra-ocular 1. Retarded growth 2. Skin disorders 3. Effect on bone

Question 496

Describe Bitot's spots, conjunctival xerosis and keratomalacia

Answer 496

Bitot's spots: foamy whitish cheese-like tissue spots, cause severe dryness Conjunctival xerosis: conjunctiva becomes dry and non-wettable, appears muddy and wrinkled Keratomalacia: cornea becomes soft, may burst open, if eye collapses vision lost

Question 497

What is carotenemia?

Answer 497

Impairment of conversion of carotene to Vit A due to inborn metabolic error or hepatic disease Generalised yellowish skin and mucosa Excessive deposition of carotene due to high intake of carotene containing foods

Question 498

What are the 5 oral manifestations of vit A?

Answer 498

1. Xerostomia 2. Altered taste 3. Gingival hypertrophy 4. Dec. ameloblast and odontoblast formation 5. Disrupted enamel formation, irregular tubular dentine formation

Question 499

What is unique about Vit d?

Answer 499

Only fat soluble vitamin humans can synthesise

Question 500

What are vit D3 and D2?

Answer 500

D3: cholecalciferol D2: ergosterol

Question 501

Describe the metabolic synthesis of vit D3

Answer 501

Cholesterol converted to 7-dehydrocholesterol UV rays convert 7DC to cholecalciferol which is then hydrolysed in kidney and liver to active 1,25-dihydroxycholecalciferol

Question 502

What are the dietary sources of vit D3?

Answer 502

``` Cheese Butter Margarine Fish Fortified milk and cereals ```

Question 503

What are the RDAs for vit D?

Answer 503

Pregnant/breastfeeding/>65: 0.01mg/d | 6m-5y: 0.007-0.0085mg/d

Question 504

What are the 7 signs and 2 complications of vit D toxicity?

Answer 504

1. Constipation 2. Anorexia 3. Fatigue 4. Muscle weakness 5. Irritability 6. Vomiting 7. Dehydration Complications 1. Kidney stones 2. Kidney failure

Question 505

What are the 5 functions of vit D?

Answer 505

1. Ca and K balance 2. Bone and tooth development: enhance Ca absorption in gut and renal tubules 3. BP regulation 4. Immunity 5. Cell differentiation

Question 506

What are the affects of vit D deficiency?

Answer 506

Rickets: dec. Ca, poor calcification, deformed bones Osteomalacia: post-menopause, bone pain, weak muscle Inc. risk of osteoporosis

Question 507

What are the 4 oral manifestations of vit D deficiency?

Answer 507

1. Teeth: developmental abnormalities in enamel and dentine 2. Higher risk of caries 3. Enamel hypoplasia 4. Pulp: high horns, large chamber, delayed closure of root apices

Question 508

What are the 2 types of vitK and their sources?

Answer 508

K1: plant; spinach, cabbage, broccoli, cauliflower, wheat germ, tomatoes, potatoes, carrots K2: synthesised by intestinal bacteria from milk, fish, meat

Question 509

What is the RDA for vitK?

Answer 509

0.001 mg/d per kg weight

Question 510

What are the 2 functions of vitK?

Answer 510

1. Production of blood clotting factors II, V, VII, IX, X | 2. Bone mineralisation: VitK-dependent proteins; osteocalcin, matrix Gla protein, protein S role in matrix formation

Question 511

What are the effects of vitK deficiency?

Answer 511

Inc. prothrombin time and risk of haemorrhage | Bone deformation

Question 512

What is the oral manifestation of vitK deficiency?

Answer 512

Uncontrollable gingival/mucosal bleeding

Question 513

What is VitE? Generally describe function and how it works

Answer 513

Family of 8 naturally occurring compounds Powerful antioxidant, present in anti ageing products Intercepts free radicals, prevents destruction of cell membrane

Question 514

What are the sources of VitE?

Answer 514

Egg, fish, liver, butter | Soybean, palm oil, sunflower, corn, olive, nuts, green leafy veg, whole grain

Question 515

What is the RDA for vitE?

Answer 515

Men: 4mg/d Women: 3mg/d

Question 516

What is the function of vitE?

Answer 516

Promote vasodilation Inhibit platelet aggregation Prevent atherosclerosis by preventing oxidation of LDLs

Question 517

What are the effects of a VitE deficiency?

Answer 517

Premature ageing: hair, nails, skin Inc. risk of CVD Degenerative changes in blood capillaries

Question 518

Name the B complex vitamins

Answer 518

``` B1: thiamin B2: riboflavin B3: niacin B5: pantothenic acid B6: pyridoxamine B12: cobalamin Biotin Folic acid ```

Question 519

What are the sources of vitBs?

Answer 519

Yeast, grain, rice, fish, veg, meat

Question 520

What is the effect of toxicity of B6?

Answer 520

>5.0mg/d Nerve damage, difficulty walking Numbness in feet and hands

Question 521

What are the 4 functions of vit Bs?

Answer 521

1. Co-enzymes 2. Energy metabolism: B1-6 and biotin 3. RBC synthesis: folate, B12 4. Homocysteine metabolism: folate, B6 and 12

Question 522

What is the effect of B1 deficiency?

Answer 522

Beriberi: after 10 days Weakness, nerve degeneration, irritability, poor leg/arm coordination, loss of nerve transmission Oedema, enlarged heart, heart failure Due to poor glucose metabolism

Question 523

What is the effect of B2 deficiency?

Answer 523

Ariboflavinosis: occurs within 2 months Glossitis, cheilosis, stomatitis, nervous system disorder

Question 524

What does B3 deficiency cause?

Answer 524

Pellagra | Scaly sores, mucosal changes and mental syndrome

Question 525

What does B6 deficiency result in?

Answer 525

``` Depression Nerve irritation Skin disorders Vomiting Impaired immune system ```

Question 526

What does B12 deficiency cause?

Answer 526

Megaloblastic anaemia | Large and irregular RBCs

Question 527

What oral manifestations do vit B deficiencies result in?

Answer 527

B2: glossitis, stomatitis, cheilosis B12: aphthous ulcer

Question 528

What are the sources of vitC in humans?

Answer 528

Citric fruits

Question 529

What is the RDA for vit C?

Answer 529

40 mg/d

Question 530

What 3 things does toxicity of vit C result in?

Answer 530

>1000 mg/d 1. Stomach pains 2. Diarrhoea 3. Flatulence

Question 531

What are the 5 functions of vit C?

Answer 531

1. Antioxidant 2. Enhance iron absorption 3. Synthesis of collagen 4. Immune: reduce cold duration by 1 day 5. Wound healing

Question 532

What does vit C deficiency cause?

Answer 532

Scurvy: 20-40 day deficient Fatigue, pinpoint haemorrhages Bleeding gums and joints

Question 533

What are the oral manifestations of vit C deficiency?

Answer 533

Loosening of teeth and tooth loss | Gum bleeding, gingivitis

Question 534

What are the 3 most important trance minerals?

Answer 534

1. Iodine: thyroid function 2. Iron: haemoglobin 3. Fluoride: bone and teeth

Question 535

What are the 2 most important major minerals?

Answer 535

1. Phosphorus: DNA | 2. Calcium: bones

Question 536

What are the 5 sources of fluoride?

Answer 536

1. Toothpaste 2. Fluoridated water 3. Mouthwash 4. Food processed w/ fluoridated water 5. Fluoride supplements

Question 537

What is the function of fluoride?

Answer 537

Anti-cariogenic: prevent bacterial adhesion suppress cariogenic bacteria change enamel crystalline structure

Question 538

Describe the changes in enamel crystalline structure due to fluoride

Answer 538

HA -> FA Larger crystals Higher pKa to dissolve

Question 539

What is the result of fluoride toxicity?

Answer 539

Fluorosis Chronic Mottled enamel w/ scattered, irregular white flecks

Question 540

Define inherited metabolic disorder

Answer 540

Metabolism disorder caused by mutation in gene that codes for enzyme resulting in enzyme deficiency and breakdown of metabolic pathway

Question 541

What are the 6 clinical presentations in neonates of IEMs and 5 in young children?

Answer 541

1. Vomiting 2. Seizures 3. Irritability 4. Poor feeding 5. Breathing disorder 6. Abnormal tone 1. Recurring vomiting 2. Dysmorphic features: characteristic facial expression 3. Mental retardation 4. Seizures 5. Developmental delay: milestones

Question 542

What are the 7 categories of IEMs?

Answer 542

1. AA metabolism disorders 2. Carbohydrate metabolism disorders 3. FAO disorders 4. Lysosomal storage disorders 5. Peroxisomal disorders 6. Urea cycle disorders 7. Mitochondrial disorders

Question 543

What is Von Gierke's disease?

Answer 543

IEM characterised by deficiency of glucose-6-phosphatase Renders glycogen stores of body inaccessible Lack free glucose Glucose synthesis from glucose-6-phosphate via gluconeogenesis hampered

Question 544

What are the affects of Von Gierke's disease?

Answer 544

1. Hypoglycaemia 2. Lactic acidosis 3. Hepatomegaly

Question 545

Describe galactosaemia

Answer 545

Deficiency of galactose-1P uridyltransferase | Converts galactose-1P to glucose-1P which is subsequently converted to 6P and enters glycolysis

Question 546

What are the effects of galactosaemia?

Answer 546

Child unable to utilise galactose component of lactose in milk Accumulation of galactose-1P in blood, diarrhoea, vomiting, mental retardation, develop cataracts

Question 547

What is the result of a deficiency of liver fructokinase or fructose-1P aldolase?

Answer 547

Fructokinase: convert fructose to fructose-1P Fructose-1P aldolase: fructose-1P to glyceraldehyde Fructose intolerance Results in an accumulation of fructose-1P which inhibits both glycogenolysis and gluconeogenesis leading to hypoglycaemia

Question 548

What are 2 AA metabolism disorders?

Answer 548

Alkaptonuria: black urine | Maple syrup urine disease

Question 549

Describe alkaptonuria

Answer 549

Defect in breakdown of tyrosine and phenylalanine Causes accumulation of homogentisic acid which is excreted in urine and oxidises on standing giving urine black colour This can lead to arthritis due to build up in cartilage

Question 550

Describe maple syrup urine disease

Answer 550

Defect in branched AA metabolism causing accumulation of keto-acids in urine If left unmanaged can lead to physical and mental retardation

Question 551

Describe phenylketonuria

Answer 551

Defect in phenylalanine hydroxylase causes impaired conversion of phenylalanine to tyrosine Phenylalanine accumulates in blood and excreted in urine (aminoaciduria)

Question 552

What are the signs of phenylketonuria?

Answer 552

Irritability Vomiting Mental retardation Red. melanin formation

Question 553

What are the 6 presentations of phenylketonuria?

Answer 553

1. Mental retardation 2. Hypopigmentation 3. Developmental delay 4. Musty odour 5. Autism 6. Epilepsy

Question 554

What is familial hypercholesterolaemia?

Answer 554

Disorder caused by red. number functional LDL receptors in liver

Question 555

What are the 3 effects of hypercholesterolaemia and treatment options?

Answer 555

1. Premature coronary heart disease 2. Tendon xanthomas 3. Severe hypercholesterolaemia Modify diet, fibrates, statins, bile acid binding resins