Metabolism Flashcards

Question

What are the increased health risks associated with obesity?

Answer 1

Hypertension Heart disease Stroke Type 2 Diabetes Mellitus Some cancers Gall bladder disease Osteoarthiritis

Answer 2

The maintenance of a stable internal environment within set limits, in a dynamic equilibrium.

Answer 3

A failure to maintain homeostasis.

Answer 4

A highly integrated network of chemical reactions that occur within cells.

Answer 5

- Energy for cell function and biosynthesis - Building block molecules - Organic precursor molecules - Biosynthetic reducing power

Answer 6

The diet Synthesis in the body from precursors Body tissue storage

Answer 7

Degradation to release energy in all tissues Synthesis of cell components, all except RBCs Storage: liver, adipose, skeletal muscle Interconversion to other nutrients Excretion

Answer 8

The breakdown of larger molecules into smaller ones

Answer 9

Exergonic, oxidative (releases H atoms and reducing power), produces intermediary metabolites

Answer 10

Smaller molecules being built up into larger ones from intermediary metabolites

Answer 11

Uses energy released from catabolism (endergonic), reductive (uses H released in catabolism, uses intermediary metabolites.

Answer 12

The ATP/ADP cycle releases energy by oxidation for movement membrane transport biosynthesis growth and repair

Answer 13

Many of them have a high energy of hydrolysis

Answer 14

A high energy fuel store that can be used immediately when ATP is low It is created when ATP levels are high Sudden vigorous muscle activity

Answer 15

Creatine Kinase

Answer 16

Skeletal muscle mass

Answer 17

When electrons are removed (hydrogen atoms - H+ and e-) The products are transferred to carrier molecules

Answer 18

Complex molecules derived from vitamins (B), which are reduced by the addition of 2 H atoms

Answer 19

NADH + H+ NADPH + H+ FAD2H

Answer 20

The concentration of ATP falls and the concentration of ADP and AMP increases

Answer 21

The concentration of ATP rises

Answer 22

Hydrophilic: do not readily cross cell membranes Partially oxidised: need less oxygen thsn fatty acids for complete oxidation

Answer 23

A high energy signal It signifies that the cell has adequate energy for its immediate needs

Answer 24

Low energy, need more

Answer 25

NADPH, NADH, FAD2H

Answer 26

NAD+. NADP+ and FAD

Answer 27

C(H₂0)_n

Answer 28

Keto C=O Aldehyde -CHO Hydroxyl -OH

Answer 29

Triose, pentose, hexose 3Cs to 9Cs

Answer 30

The aldehyde or ketone group reacts with a hydroxyl group

Answer 31

Anomeric C atom

Answer 32

Two monosaccharides joined together by a condensation reaction eliminating a molecule of water and forming an O-glycosidic bond.

Answer 33

Lactose: galactose and glucose Maltose: glucose and glucose Sucrose: fructose and glucose

Answer 34

If the aldo and keto groups from both molecules are involved in forming the glycosidic bond

Answer 35

A polymer of monosaccharide units linked by glycosidic bonds

Answer 36

Homo polymers

Answer 37

Glycogen Starch Cellulose

Answer 38

Glucose polymer Animals Alpha 1,4 and alpha 1.6 glycosidic bonds Highly branched Stored in the liver and skeletal muscle

Answer 39

Glucose polymer Found in plants Amylose, alpha 1, 4 links Amylopectin, alpha 1,4 and alpha 1.6 Hydrolysed to maltose and glucose in GI system

Answer 40

Glucose polymer Plant cell walls, structural role Beta 1,4 linkages Linear polymer Needed in human diet as fibre for good GI function Humans can not digest, as they do not have the required enzymes to process the beta 1,4 links

Answer 41

Glycogen and starch, by glycosidase enzymes Glucose, maltose, dextrins (smaller polysaccharides)

Answer 42

Salivary amylase in the buccal cavity Pancreatic amylase in the duodenum

Answer 43

The duodenum and jejunum

Answer 44

Found on brushborder membrane of epthelial cells of duodenum and jejunum They are large glycoprotein complexes

Answer 45

Lactase Isomaltase/sucrase Glycoamylase

Answer 46

Lactose intolerance Can not digest the lactose in milk products properly

Answer 47

Lactose persists in the colon As lactase activity is low Lactose has an osmotic effect drawing water into the lumen This causes diarrhoea Bacteria in the colon break down lactose This produces gases such as CO2, H2, and CH4 This causes bloating and discomfort

Answer 48

Active transport into the epithelial cells of the intestine Facilitated diffusion from epithelium to blood Uses GLUT transport proteins, which can be hormonally controlled

Answer 49

180g per day 40g in tissues with an absolute requirement 140g per day in the CNS Variable amounts needed in other tissues for specific functions, eg glycerol phosphate for TAGs in adipose is provided by glucose metabolism

Answer 50

Red blood cells White blood cells Kidney medulla Lens of the eye CNS prefers glucose but can use ketone bodies too

Answer 51

Central pathway in sugar catabolism, exergonic 10 enzyme catalysed steps Cytoplasm Active in all tissues Can be anaerobic Start and end products either C3 or C6 No loss of CO2

Answer 52

Generate ATP, 2 net (4 produced, 2 used) Generate NADH from NAD+, reduce Building block molecules for anabolism Useful C3 intermediates Produce pyruvate by oxidising glucose Substrate level phosphorylation

Answer 53

1, 3 and 10 Step 1: Hexokinase in muscle, Glucokinase in the liver Step 3: Phosphofructakinase Step 10: Pyruvate Kinase

Answer 54

Glucose to glucose 6 phosphate. Uses ATP Makes the sugar ionic so it can not cross the plasma membrane, increases reactivity

Answer 55

Conversion of fructose 6 phosphate, to fructose 1, 6 bisphosphate Committing step, irreversible

Answer 56

7 and 10 through substrate level phosphorylation

Answer 57

Phosphoenolpyruvate to pyruvate, producing ATP x2 irreversible

Answer 58

Glycerol phosphate: from DHAP, needed for glycerol synthesis 2, 3 BPG: Hb regulator, from 1, 3 BPG in glycolysis

Answer 59

Pyruvate is reduced to lactate by lactate dehyrdogenase Produces NAD+ Produces ATP

Answer 60

Released into circulation Converted back to pyruvate and oxidised to CO2 in heart Or converted to glucose in the liver

Answer 61

1mM Lactate production = utilisation

Answer 62

Hyperlactaemia: 2mM - 5mM in the blood. Below renal threshold, no change in blood pH, within buffering capacity. Lactic acidosis: above 5mM, above renal threshold, blood pH lowered.

Answer 63

Liver Soluble enzymes

Answer 64

By soluble enzymes in the liver Fructose to fructose 1 phosphate then to 2 glyceraldehyde 3 phosphate/DHAP which feeds into glycolysis

Answer 65

Fructokinase missing, causes fructose to build up in urine, essential fructosuria, no clinical signs Frctos intolerance, aldolase missing, fructose 1 phosphate accumulated inliver, damage, treatment, remove fructose from diet

Answer 66

Galactokinase, galactose to galactose 1 phosphate Galactose 1 phosphate uridyl transferase, to glucose 1 phosphate, which can transfer into glycolysis

Answer 67

Individuals are unable to utrilise galactose obtained in the diet because of a lack of galactokinase of glactose 1 phosphate uridyl transferase

Answer 68

Either galactokinase or galactose 1 phospahte uridyl transferse can be deficient. Loss of transferase is more common Loss of transferase is more serious because galactose 1 phosphate accumulates which is toxic to the liver, kidney, brain as does galactose.

Answer 69

Galactose is reduced to galactitol by aldose reductase, which depletes some tissues of NADPH.

Answer 70

NADPH is needed in the eye to keep cysteine residues in proteins reduced. If there is a lack of NADPH, S-S bonds form, cross linking proteins, damaging the len structure and causing cataracts. Non enzymatic glycosylation of lens proteins due to high galactose concentration - may also contribute to cataracts Accumulation of galactose and galactitol in the eye leads to increased intraocular pressure, may cause glaucoma

Answer 71

No lactose in diet Should be detected early for effective management. Heel prick test

Answer 72

PRODUCE NADPH IN THE CYTOPLASM PRODUCE C5 SUGARS FOR NUCLEOTIDES Reducing power for anabolic processes like lipid synthesis In RBCs maintain free -SH groups on cysteine residues Detoxification

Answer 73

Liver Red blood cells Adipose Dividing tissues

Answer 74

Glucose 6 phosphate to 5C sugar phosphates by glucose 6 phosphate dehydrogenase and 6 phosphogluconte dehydrogenase. This reaction produces NADPH and CO2. Any unused C5 sugar phosphates back to glycolysis.

Answer 75

Reduced activity of this rate limiting enzyme. Low levels of NADPH. X linked recessive , point mutation.

Answer 76

Lack of NADPH in cells Can not maintain free -SH cysteine residues Disulphide bridges form. Hb and other proteins cross linked Heinz bodies, insoluble aggregates. GSSG (glutathione) Premature destruction of RBCs, haemolysis. Jaundice etc complications Acute haemolytic episodes from antimalarials, oxidants

Answer 77

Pyruvate dehyrdogenase, a multi enxume complex.

Answer 78

Mitochondrial matrix

Answer 79

Irreversible, can't convert acetyl coA back to pyruvate for gluconeogenesis Loss of CO2

Answer 80

Under certain conditions acetyl coA from B oxidation of FAs is used rather than from glucose in stage 3 catabolism, acetyl coA allosterically inhibits PDH Reaction is energy sensitive: ATP/NADH inhibit, ADP promotes allosterically Activated when there is a lot of glucose, insulin activates by dephosphorylating PDH

Answer 81

A central pathway in the metabolism of sugars, fatty acids, ketone bodies, alcohol and aminoacids.

Answer 82

C4 intermediates: Haem and glucose synthesis, non essential amino acids (from succinate, fumarate, oxaloacetate) C5 intermediates: non essential amino acids (from alpha ketoglutarate) C6 intermediates: fatty acids (from citrate)

Answer 83

Oxidative Produces NADH and FAD2H Needs NAD+, FAD and oxaloacetate Main function is to break C-C bond in acetate and oxidise the C atoms to CO2 Some ATP produced directly by substrate level phosphorylation Produces C4 acids that are interconvertible

Answer 84

2 turns 6 NADH 2 FAD2H 2 GTP (after ETC 32 ATP)

Answer 85

ATP/ADP ratio NADH/NAD+ ratio Activated by low energy, inhibited by low energy Irreversible step, isocitrate dehydrogenase, activated by ADP, inhibited by NADPH

Answer 86

All C-C bonds have been broken, and C atoms oxidised to CO2. All C-H bonds have been broken and H atoms have been transferred to NAD+ and FAD. The energy is either in ATP/GTP formation, 2 in each of glycolysis and TCA cycle Chemical bond energy is in the e- in NADH and FAD2H.

Answer 87

Takes place on the inner mitochondrial membrane Electron transport is coupled with ATP synthesis NADH and FAD2H are reoxidised O2 is required, it is reduced to water Large amounts of ATP are produced

Answer 88

NADH and FAD2H contain high energy electrons that can be transferred to oxygen through a series of carrier molecules with the release of large amounts of free energy. The free energy released in ETC drives ATP synthesis from ADP and Pi

Answer 89

Carrier molecules transferring electrons to molecular oxygen are in a series of 4 specialised protein complexes Spanning inner mitochondrial membrane Electrons are transferred from NADH and FAD2H through the complexes releasing free energy Three of the complexes are proton translocating complexes.

Answer 90

Free energy from electron transport is used to pump H+ ions across the membrane into the intermembrane space Inner membrance impermeable H + Concentration outside inner membrance increases Creates electrochemical gradient Which is known as the proton motive force

Answer 91

NADH : 3 FAD2H: 2

Answer 92

Energetically favourable for protons to move back to matrix due to pmf Can only return through ATP synthase, inner mitochondrial membrane impermeable to H+ ions Energy from movement drives the synthesis of ATP from ADP and Pi Greater PMF more ATP made

Answer 93

5 moles of ATP from 2 NADH 3 moles of ATP from 2 FAD2H

Answer 94

ET and ATP synthesis do not occur without each other. When [ATP] is high, ATP synthesis stops as [ADP] is low, a lack of substrate. This stops H+ transport back to mitochondria. H+ concentration outside increases so that more can not be pumped out. In absence of proton pumping, ETC stops. REVERSE OCCURS WHEN ATP IS LOW

Answer 95

They block electron transport by preventing oxygen accepting electrons. Examples are cyanice, carbon monoxide. They have a higher affinity

Answer 96

Function is to uncouple ET from ATP synthesis to produce heat Proteins in the inner mitochondrial membrane UCPs 1 - 5 (first 3 most important) UCP1: thermogenin, brown adipose tissue, non shivering thermogenesis

Answer 97

Increase the permeability of the inner mitochondrial membrane to protons Protons being pumped out by ET can re enter without the synthesis of ATP. Pmf is dissapated as heat Makes up 20-25% of BMR

Answer 98

Dinitrophenol Dinitrocresol

Answer 99

Sympathetic nervous system Stimulates lipolysis releasing FAs for oxidation in brown adipose NADH and FAD2H produced Drive electron transport and produce pmf Noradrenalin activates UCP1 Pmf dissapated as heat

Answer 100

O: membrane associated complexes. SL: soluble enzymes O: inner mitochondrial membrane. SL: cytoplasm and mitochondrial matrix O:Indirect energy coupling, generation and usage of a pmf. SL: Direct energy coupling through formation of a high energy of hydrolysis bond O: Can not occur without oxygen. SL: can occur to limited extent with oxygen. O: Major process ATP synthesis. SL: Minor process for ATP synthesis

Answer 101

Generally insoluble in water, hydrophobic Soluble in organic solvents No general formula Most contain C, H and O (phospholipids P and N too) More reduced than carbohydrates (less O and more H per C atom)

Answer 102

1. FATTY ACID DERIVATIVES: fatty acids (fuel molecules), triacylglycerols (fuel storage and insulation), phospholipids (components of membranes and plasma lipoproteins), eicosanoids (local mediators) 2. HYDROXY-METHYL-GLUTARIC ACID DERIVATIVES (C6 compound): ketone bodies (C4, water soluble fuel molecule), cholesterol (C27, membranes and steroid hormone synthesis), cholesterol esters (cholesterol storage), bile acids and salts (C24, lipid digestion) 3. FAT SOLUBLE VITAMINS: A, D, E, K

Answer 103

By pancreatic lipase To release glycerol and fatty acids Complex process Needs bile salts Needs protein factor: colipase

Answer 104

Enters the blood stream Transported to liver Phosphorylated by glycerol kinase Either goes to TAG synthesis Or oxidised to DHAP which enters glycolysis

Answer 105

Long chain molecules Even no of C atoms Hydrophobic Highly reduced - so ideal for energy storage Saturated or unsaturated Saturated are non essential, can be synthesised

Answer 106

Stored anhydrously in adipose tissue Store of fuel for prolonged aerobic exercise, starvation and pregnancy

Answer 107

Insulin Glucagon, adrenaline, growth hormone, thyroxine, cortisol

Answer 108

Bound to albumin

Answer 109

Heart muscle liver skeletal muscle

Answer 110

Links to coenzyme A outside the mitochondrion Linked via S atom in free -SH group Forms a high energy of hydrolysis bond This process needs ATP and Fatty acyl coA synthase

Answer 111

Cartinine transport shuttle- also helps to regulate the rate of FA oxidation Converted to acyl cartinine and back Inhibited by malonyl coA which is an intermediate in FA synthesis Defect in transport causes poor exercise tolerance, lipid droplets in muscle

Answer 112

Sequence of reactions that oxidises the fatty acid Removes an acetate Cucled repeatedly until only 2 carbons remain Needs NAD+ and FAD Needs oxygen for ETC to reoxidise NADH and FAD2H No direct ATP synthesis All intermediates linked to co A.

Answer 113

Acetoacetate B-hydroxybutarate (synthesised in the liver from acetyl coA) Acetone: spontaneous non enzymatic decarboylation of acetoacetate

Answer 114

Usually ketones less than 1mM in the blood Increases in starvation: 2mM to 10mM (physiological ketosis) In untreated type 1 diabetes, bove 10mM

Answer 115

Water soluble So can have high plasma concentration, can cross blood brain barrier, can be excreted in urine Acetoacetate and b hydroxybutarate are quite strong organic acids so can cause acidosis Acetone is volatile and can be excreted via the lungs (on breath of untreated type 1 diabetics for example)

Answer 116

Fatty acids for oxidation in the liver: substrate Plasma insulin:glucagon ratio is low, activates lyase, inhibits reductase

Answer 117

Acetyl co A to HMG coA via synthase enzymes HMG coA to acetoacetate via lyase

Answer 118

Catabolism of Fatty acids Sugars Alcohol Certain amino acids

Answer 119

It can be oxidised in stage 3 of catabolism, the TCA cycle It is an important intermediate in lipid biosynthesis (anabolism), in the liver and some adipose tissue

Answer 120

TAGs: 15kg Glycogen: 400g Muscle protein: 6kg

Answer 121

1. Using ATP is phosphorylated to glucose 6 phosphate by hexokinase/glucokinase 2. Glucose 6 phosphate to glucose 1 phosphate by phosphoglucomutase 3. Glucose 1 phosphate + UTP + water makes UDP glucose (high energy) and 2 Pi 4. Glycogen (n residues) + UDP glucose makes glucogen (n+1 residues\_ and UDP. Step 4 is catalysed by glycogen synthase which adds alpha 1,4 links, and branching enzyme which adds alpha 1,6 links about every 10 units

Answer 122

Exercise in skeletal muscle. Fasting in the liver, or stress response Never degraded fully, a small amount of primer is preserved

Answer 123

Glycogen phosphorylase creates glucose 1 phosphate by attacking the alpha 1,4 bonds. Debranching enzyme attacks the alpha 1,6 bonds and releases glucose. Phosphoglucomutase moves the phosphate from carbon 1 to carbon six producing glucose 6 phosphate. This enters glycolysis in skeletal muscle. In the liver, the addition of water to glucose 6 phosphate by glucose 6 phosphatase makes glucose and Pi. Therefore glycogen in the liver supplies glucose for all tissues through the blood stream.

Answer 124

LIVER: glucose store for all tissues of the body, in response to fasting or stress. Glucose 6 phosphate to glucose by glucose 6 phosphatase. MUSCLE: glucose 6 phosphate store, can only be used by muscle as it enters glycolysis.

Answer 125

- Glycogen phosphorylase - Phosphoglucomutase Glucose 6-phosphatase in liver Increase or decreased amounts of glycogen. Tissue damage if too much storage Fasting hypoglycaemia Poor exercise tolerance Abnormal structure of glycogen

Answer 126

Allosteric control of glycogenolysis, glycogen phosphorylase: AMP activates Synthesis: glycogen synthase, activated by insulin dephosphorylating. It is inhibited by glucagon and adrenaline, which phosphorylate. Glycogen phosphorylase: activated by glucagon and adrenaline phosphorylating. Deactivated by insulin dephosphorylating.

Answer 127

The production of glucose when carbohydrates are absent.

Answer 128

Pyruvate, lactate, glycerol Essential and non essential amino acids whose metabolism involves pyruvate or TCA intermediates NOT ACETYL COA

Answer 129

Uses the reversible steps of glycolysis and bypasses the irreversible ones. Steps 1 and 3 are bypassed by thermodynamically spontaneous reactions, catalysed by phosphatases. Glucose 6 phosphatase (to make glucose) and fructose 1,6 bisphosphatase (to make fructose 6 phosphate). Step 10 is bypassed by reactions drived by ATP and GTP hydrolysis. Catalysed by pyruvate carboxylase and phosphoenolpyruvate caroxykinase (PEPCK). This produces oxaloacetate and phosphoenolpyruvate. Link to TCA

Answer 130

Response to starvation, exercise, stress Glucagon and cortisol stimulate PEPCK and glucagon stimulates Fructose 1,6 bisphosphatase Insulin inhibits PEPCK and fructose 1,6 bisphosphatase

Answer 131

Esterification Lipolysis

Answer 132

Promote: Insulin Deplete: glucagon, adrenaline, growth hormon, cortisol, thyroxine

Answer 133

From acetyl coA, using ATP and NADPH Cytoplasm Carried out by mlti enzyme complex: fatty acid synthase complex C2 units added as malonyl coA, with loss of CO2 Malonyl coA is made from acetyl coA byt acetyl coA carboxylase

Answer 134

Chylomicrons to store as TAGs

Answer 135

Allosteric regulation: citrate activates and AMP inhibits Covalent modification: Insulin activates by dephosphorylation Glucagon and adrenaline inhibit by promoting phosphorylation

Answer 136

O: removes C2. S: adds C2. O: Removed as acetyl coA. S: Added as malonyl coA with loss of CO2. O: Produces acetyl coA. S: consumes acetyl coA. O: In mitochondria. S: in cytoplasm. O: Oxidative. S: reductive, uses NADPH O: Seperate enzymes. S: enzyme complex. O: Needs small amount of ATP to activate the FA. S: needs lots of ATP to drive the process. O: Regulated indirect by FA availability. S: directly regulated by acetyl coA carboxylase.

Answer 137

protein synthesis synthesis of purines and pyrimidines in DNA and RNA small amounts of porphyrins (haem), creatine, nerotransmitters, hormones

Answer 138

PVT. TIM HALL Phenylalanine Valine Tryptophan Threonine Isoleucine Methionine Histidine (semi) Arginine (semi) Leucine Lysine Tyrosine and cysteine may become essential

Answer 139

Transamination Or deamination

Answer 140

Pyruvate Oxaloacetate Fumarate Alpha ketoglutarate Succinate Acetyl coA

Answer 141

Ketogenic amino acids are broke down to acetyl coA which makes ketone bodies by synthase and lyase. Glucogenic amino acids make the other products which can make glucose by gluconeogenesis.

Answer 142

Isoleucine, threonine, phenylalanine

Answer 143

Aminotransferases ALT, Alanine aminotransferase: GPT Alanine+alpha ketoglutarate TO glutamate+pyruvate AST, Aspartate amino transferase:vGOT Aspartate+alpha ketoglutarate TO oxaloacetate and glutamate Most use alpha ketoglutarate as keto acid 2. If oxaloacetate is used, it is converted to aspartate.

Answer 144

Liver function test

Answer 145

L and D amino acid oxidases Convert amin acids to keto acids and NH3, to ammonium ion D amino acids from diet, can't be used for protein synthesis. High activity of D amino acid oxidases in the liver. Glutaminase converts glutamine to glutamate and NH3. Glutamate dehydrogease makes alpha ketoglutarate, ammonia and reduced NAD.

Answer 146

Synthesis is promoted by insulin and inhibited by glucocorticoids Breakdown is promoted by glucocorticoids and inhibited by insulin

Answer 147

An inherited autosomal recessive disorder in which the urine contains large amounts of phenylketones produced from phenylalanine.

Answer 148

Phenylalanine hydroxylase enzyme is defective This oxidises phenylalanine to tyrosine Excess phenylalanine combines with alpha ketoglutarate to make phenylpyruvate, ketone Phenylalanine and phenylpyruvate accumulate in the blood. Phenylalanine saturates transporter LNAAT carrier, this transports amino acids across blood brain barrier. Mental reatrdation due to decreased brain metabolism. Lack of tyrosine, has to be supplemented in diet. Useful precursor for hormones (thyroid) and neurotransmitters.

Answer 149

A rare inherited autosomal recessive defet In methionine metabolism Excess homocystine in urine Caused by defect in CBS enzyme cystathionine beta synthase

Answer 150

Converts homocysteine to cystathionine, which is further converted to cysteine.

Answer 151

Methionine builds up in the plasma, as does homocystine, oxidised form Homocysteine causes disorders of connective tissue, muscle, CNS and CVA is elevated in plasma. Similar to Marfans syndrome, tight joints, intellectual disability, long limbs, near sightedness, arachnodactyly, damages FIBRILLIN

Answer 152

B6 supplement, increases deficient CBS, as cofactor B12 supplement, more homocysteine to methionine, which can be excreted. Add cysteine to diet.

Answer 153

Blurred vision Tremors Slurred speech Coma Death Removes alpha ketoglurate from the TCA cycle as reacts to form glutamate via glutamate dehydrogenase Affects the pH in CNS Interferes with neurotransmitter sunthesis and release. Commonly seen in liver disease

Answer 154

Either by synthesis of N compounds like glutamine or conversion to urea. Glutamine can be synthesised from glutamate and ammonis via glutamine synthetase, requiring ATP. It is transported to the liver and kidney where it is hydrolysed to release ammonia. In the kidney ammonia is excreted and in the liver it is converted to urea.

Answer 155

Very soluble in water Non toxic Metabolically inert High nitrogen content

Answer 156

NH2 groups of urea come from ammonium and aspartate. 5 enzymes Occurs in the liver, transported via blood to the kidney for excretion. Orthinine to citrulline in the mitochondrial matrix. To argininosuccinate and arginine.

Answer 157

Not subject to feedback inhibition Enzymes are inducible Refeeding syndrome, hyperammonaemia

Answer 158

All defects cause hyperammonaemia and accumulation or excretion of urea cycle intermediates Depends on extent of defect Vomiting, lethargy, irritability, mental retardation, seizures, coma, death Treat with low protein diet, replace essential amino acids with ketoacids that use up ammonium when converted to amino acids.

Answer 159

Diffuses from liver cells to blood to kidney where it is filtered and excreted in the urine Some urea diffuses into the intestine, bacteria break down to release ammonia which is reabsorbed Kidney failure: urea conc in blood is high, production of ammonia from urea by bacteria in the gut can cause hyperammonaemia.

Answer 160

98% as lipoprotein particles 2%, mainly fatty acids, bound non covalently to albumin

Answer 161

Atheroschlerosis Coronary artery disease

Answer 162

Small assemblies of hydrophobic lipid molecules surrounded by polar molecules (micelles) Protein components: apoproteins Spherical particles, surface coat and core Hydrophobic core: TAGs and cholesterol esters Surface coat: proteins, phospholipids, cholesterol Only stable if spherical shape is maintained: ratio of core to surface lipids. LCAT Non covalent

Answer 163

Chylomicrons: dietary TAGs from the intestine to tissue such as adipose. VLDL:Transport of TAGs synthesised in the liver to adipose for storage. LDL: Transport of cholesterol synthesised in the liver to the tissues. HDL: Transport of excess tissue cholesterol to the liver for disposal as bile salts.

Answer 164

Hydrolysed in small intestine by pancreatic lipase Fatty acids enter epithelial cells of small intestine FAs reesterified back to TAGs using glycerol phosphate from glucose metabolism. Packaged into chylomicrons with other dietary lipids Released into blood stream via the lymphatic system Carried to tissues like adipose that express lipoprotein lipase. Hydrolysed and FAs enter the adipose cells where they are converted to TAGs for storage

Answer 165

4 to 6 hours after a meal

Answer 166

They go via the thoracic duct to the left subclavian vein This bypasses the liver and hepatic portal vein

Answer 167

High LDL levels deposit cholesterol on blood vessel walls. Plaques. Risk factor for atheroschlerosis HDLs remove cholesterol from tissues Prevent excessive cholesterol build up Beneficial in blood vessels

Answer 168

Tetracyclic Can be esterified with a fatty acid, eliminated the polar OH group Major membrane component Precursor of steroid hormones Precursor of bile acids Mainly synthesised in the liver, some in the diet

Answer 169

Diacylglycerol with a phosphate group Major component of membrances Phosphate is polar Amphipathic Naturally forms micelles

Answer 170

Removes core TAGs from lipoproteins like chylomicrons and VLDLs Attached to inner surface of capillaries in tissues such as adipose and muscle Hydrolyses TAGs to fatty acids and glycerol Tissues then take up fatty acids, glycerol to the liver Insulin increases the synthesis of this enzyme

Answer 171

Lecitihin: Cholesterol AcylTransferase Restores the stability of lipoproteins Converts surface lipid to core lipid Converts cholesterol to cholesterol ester with FA derived from lecithin Defiency: unstable lipoproteins of abnormal structure. Failure of lipid transport Deposits in tissues Atheroschlerosis

Answer 172

Receptor mediated endocytosis Complex proteins on cell surface bind LDL apoprotein B100 LDL receptor with LDL taken in by endocytosis Subject to lysosomal digestion Cholesterol released inside the cell from cholesterol esters Inhibits cholesterol synthesis in cell and reduces synthesis and exposure of LDL receptors, uptake stimulated by need

Answer 173

Raised levels of one or more of the plasma lipoproteins There are 6 types, I, IIa, IIb, III, IV, V Type I: chylomicrons in fasting plasma, no link to coronary artery disease, caused by defective lipoprotein lipase Type II: raised LDL, associated with CAD may be severe, caused by defective LDL receptor Type III: Raised IDL and chylomicrons remnants, associated with CAD, caused by defective apoprotein E

Answer 174

Defect in metabolism of plasma lipoproteins Primary: inborn Secondary: acquired as a result of diet, drugs, underlying diseases like diabetes.

Answer 175

Xanthelasma: lipid deposits by eyelids Tendon xanthoma Corneal arcus in iris

Answer 176

Type II Absence - homozygous or deficiency - heterozygous of functional LDL receptors Elevated levels of LDL and cholesterol in the blood Atheroschlerosis early in life in homozygotes and later in heterozygotes

Answer 177

Oxidised LDL Macrophages engulf faulty LDLs Form foam cells Accumulate in intima of blood vessel wall lining, swelling Fatty streak - lighter patch Atheroma, swelling of vessel Initially clinically silent Swelling narrows lumen, if a thrombosis occludes the vessel, myocardial infarction if in coronary vessel.

Answer 178

Diet and lifestyle modifications first, reduce eliminate cholesterol and TAGs, more exercise If little effect Drug therapy: statins. Lower plasma cholesterol by inhibiting HMG co A reductase. Bile salt sequestrants: dispose of cholesterol by converting to bile salts. This prevents reabsorbtion in GI into hepatic portal circulation, more lost in faeces

Answer 179

Some electrons are leaked for the ETC prematurely at complexes 1 and 3 They reduce oxygen to form superoxide radicals O₂^- Superoxide radicals have an unpaired electron Free radical Highly reactive Know as Reactive Oxygen Species ROS Constantly leaking out of mirochondria so must be protected against

Answer 180

Superoxide radicals converted to hydrogen peroxide by SUPEROXIDE DISMUTASE (SOD) Hydrrogen peroxide converted to water and oxygen by CATALASE ROS cause damage to DNA, protein and membranes

Answer 181

HYDROXYL RADICALS, -OH: produced in all cells. By ionising radiation, from hydrogen peroxide with addition of iron ions. Damage to cells membrane and can't be eliminated by enzymes. NITRIC OXIDE, NO: produced from arginine by the inducible enzyme nitric oxide synthase (iNOS). PEROXYNITRITE, ONOO-: produced when nitric oxide and oxygen react. Involved in inflammation EXOGENEOUS: Antimalarials like primaquine, powerful oxidants, dangerous in G6PDH. Paracetamol overdose. Paraquat, a herbicide, causes superoxide radical production.

Answer 182

Glutathione (GSH), trispeptide, anti oxidant. Free -SH on cysteine are oxidised to GSSG, donate their Hs. Abundant in cells. Recycled by reducing with NADPH, which is produuced by glucose 6 phosphate dehyrdogenase. Antioxidant vitamins A C and E Flavenoids: polyphenols, beta carotene Minerals such as selenium and zinc

Answer 183

Neutrophils and monocytes When stimulated release an oxidative burst Enzyme: NADPH oxidase Cell usually destroyed As is surrounding bacteria/ fungi

Answer 184

What a Drug Does to the body What the body does to the drug

Answer 185

Primidone to phenobarbitone Pethidine to norpethidine Codeine to morphine

Answer 186

ADME Adsorption Distribution Metabolism Elimination.. of a drug

Answer 187

A reactive group is exposed or added to the parent molecule Generates a reactive intermediate Most common reactions: reduction, oxidation, hydrolysis Cytochrome p450, complex enzyme system High energy cofactor, NADPH Some bypass phase 1 as they already have a reactive group, for example morphine. Straight to phase 2

Answer 188

Conjugation with a water soluble molecule to form a water soluble complex Glucaronic acid most commonly Suplhate ions Glutathione High energy co factor: UDPGA (uridine diphosphate glucaronic acid)

Answer 189

Prolonging of anaesthesia effects

Answer 190

How chemical agents affect the functioning of living systems

Answer 191

Study of the drug effects in a large population. Reporting of adverse drug reactions (ADRs) post marketing eg thalidomide

Answer 192

CYP Complex enzyme system 50 different haem containing enzymes Polymorphisms in the population Isoform CYP3 A4 is most important, 55% of drug metabolism Co factor is NADPH

Answer 193

GENETICS: Differences in the level of expression of metabolic enzymes May lack a gene that codes for an enzyme Polymorphisms Different times to metabolise drugs Gene deletions Slow acetylators: lack enzyme that acetylates in phase II. Low levels of pseudocholinesterase enzymes in plasma: affects ability to metabolise drugs with an ester bond, such as some anaesthetics. ENVIRONMENT: Inhibition: other drugs: polytherapy, cranberry, grapefruit juice Induction: increased metabolism of other drugs, ethanol, nicotine, barbiturates, some pesticides

Answer 194

Substances absorbed in the lumen of the ileum Enters venous blood which drains into the hepatic portal vein Direct to the liver, main site of drug metabolism All necessary enzyme systems Any drug absorbed from the ileum may be mostly meatbolised in first pass through liver. Only small amount passes to the rest of the circulatory system 90% of paracetamol metabolised in first pass, so large dose of 1g is needed.

Answer 195

Alcohol to acetaldehyde by alcohol dehydrogenase Acetaldehyde to acetate (to acetyl coA) by aldehyde dehydrogenase Complete oxidation needs NAD+, forms NADH Aldehyde dehydrogenase has a low Km so keeps toxic acetaldehyde to a minimum CYP2E1 also metabolises alcohol via oxidation, and is inducible

Answer 196

NAD+ is used for fatty acid oxidation, conversion of lactate to pyruvate and glycerol metabolism So stimulates fat deposition, inadequate amounts for beta oxidaiton Lactate builds up, could cause lactic acidosis Reduces ability of the kidney to excrete uric acid, urate may build up in tissues causing gout Gluconeogenesis cannot be activated. Fasting hypoglycaemia

Answer 197

Not enough NAD+ to be oxidised Increase fatty acid and ketone body synthesis Converts to TAGs: fatty liver as lack of lipoproteins Can cause ketoacidosis

Answer 198

Toxic acetaldehyde damages liver cells. Alcoholic hepatitis/cirrhosis Leaky plasma membrane AST and ALT in blood, liver function test Reduced liver function can result in: Decreased: = uptake of conjugate bilirubin, hyperbilirubinaemia, Jaundice =urea production, hyoerammonaia and high glutamine =protein synthesis, low albumin (oedema), clotting factors (slow clotting) and lipoproteins (fatty liver)

Answer 199

Indirect: likely vitamin and mineral deficiencies, inadequate protein and carbohydrate uptake, CNS Direct effect: on GI tract Loss of appetite, diarrhoea, impaired absorption of nutrients due to damage of lining cells (vitamin K, folic acid, haemotological problems, pyridoxine and thiamine, neuro symptoms) Thiamine deficiency can lead to Wernicke Korsakoff syndrome with mental confusion and unsteady gait

Answer 200

Disulfarim Aldehyde dehydrogenase inhibitor If alcohol is consumed, acetaldehyde accumulates in the blood, giving hangover symptoms

Answer 201

Straight to phase 2 metabolism Conjugates with glucaronide or sulphate

Answer 202

Conjugation in phase 2 by glutathione or sulphate is quickly saturated Undergoes phase 1 metabolism Produces toxic metabolite NAPQI Toxic to hepatocytes Phase II conjugation with glutathione, an important antioxidant, subject to ROS attack Liver failure over several days Treatment with N-acetylcysteine, an antioxidant, RAPIDLY

Answer 203

Glucose/glycogen: glucose used by all cells, preferred fuel. Only 12g in solution can support CNS for 2 hours. Stored as glycogen in liver and muscle. Only liver glycogen can be used by the CNS. Fatty acids/ketone bodies: many cells except RBCs and CNS can use fatty acids as fuels. Fatty acids from TAGs in adipose can supply fuel for two months, the main fuel reserves. Fatty acids can be converted to ketones for CNS fuel when glucose is low in starvation. Proteins can be hydrolysed to amino acids that can be converted to glucose, ketone bodies or directly oxidised.

Answer 204

Nervous, by action potentional. Afferent to brain, efferent from brain. Endocrine, by hormones Paracrine, local hormones via ducts, exocrine Autocrine, agents being released affect the releasing cell, self control

Answer 205

Communication Control centre Receptor Effector

Answer 206

Sensors that detect stimuli such as changes to the internal environment Usually specialised nerve endings such as thermoreceptors and chemoreceptors Sensors communicate input to the control centre via afferent nerves

Answer 207

Establishes the reference set point Analyses afferent input Determines appropriate response Examples in the brain: Hypothalamus in the diencephalon: endocrine system Medulla oblongata in the brain stem: ventilation and CVS control Trauma to these regions is usually fatal

Answer 208

Agents that cause change The control centre produces an output Ouput is communicated by the efferent pathway to the effectors Eg sweat glands are activated to produce more sweat causing heat loss In paraplegic patients heat loss is affected

Answer 209

Stimulus produces a response which increases its effect Forces system out of ocntrol Rapid catastrophic change Exampkes: blood clotting, ovulation

Answer 210

When the output/effect affects the control centre

Answer 211

Output inhibits functino of the control centre Effector opposes stimulus Stabilises control systems can control set point in fine limits In most homeostatic control mechanisms Tendency to overshoot set point several times, hunting behaviour Examples: insulin and hyperglycaemia, HPA axis

Answer 212

Rather than the set point being fixed it can change over time Cortisol: levels vary throughout the day. Peak at 7am, trough at 7pm. CIRCADIAN RHYTHM. So time should always be noted when taking a cortisol sample, when repeated shouled be at the same time of day, of 24hour urine. Menstrual cycle: woman's core body temperature varies in the cycle. Sudden increase in core body temperature is a marker for ovulation. Biological clock in brain: suprachiasmatic nucleus in hypothalamus, small group of neurones. Natural diurnal cycl. Zeitgabers, keys from the envuronment keep us on 24 hours, long haul flights mismatch. Melatonin hormone in pineal gland helps set clock, no light on retina stimulates melatonin.

Answer 213

chemical signals produced in endocrine glands or tissues, that travel in the blood stream to cause an effect on tissues.

Answer 214

Change in concentration of hormones causes a cell response About 30 seconds to reach all body parts Only interact where there are receptors Can have different effects in differet places Good for coordinated multiple responses Path: endocrine tissue releases hormone, transported in blood to target cells, receptors and respsonse, inactivation of chemical by liver or sometimes kidney

Answer 215

Polypeptide: short or long chains of amino acids, largest group, insulin, glucagon, growth hormone, placental lactogen Steroid: all derived from cholesterol, cortisol, aldosterone, oestrogen, testosterone. Classified by carbon number Amino acid derivatives: small molecules synthesised from amino acids, thyroid hormones, adrenaline (a catecholamine) Glycoprotein:large protein molecules with carbohydrate side chains. Anterior pituitary hormones. LH, FSH, TSH

Answer 216

Polypeptide, glycoprotein and adrenaline: relatively hydrophilic and are transported in the blood by dissolving in the plasma. Steroid and thyroid hormones are lipophilic and need specialised transport proteins like thyroxine binding globulin or albumin

Answer 217

Effect of a hormone depends on concentration in the blood stream Only unbound or free hormones can interact with receptors Bind to specific high affinity receptors on or in the cell. Hormones that can cross cell membrance and are lipophilic bind to receptors inside the cell. Hydrophilic hormones bind to a receptor on the cell surface. Then binding hormon triggers a change i the target cells, which may be in enzyme/functional activity (short term) or gene expression (long term). Cell surface receptors often trigger a secondary messenger that influences the cells activity. Some hormones have one major target tissue whereas others have many.

Answer 218

Negative feedback One hormone controlling another Releasing or inhibiting hormones Inactivating hormones

Answer 219

Hormones constantly lost from circulation as they are excreted or broken down Secretion rate must be adjusted to maintain concentration Rate of secretion directly affected by blood concentration If the concentration falls below a critical levels hormone secretion increases until the correct level is acheived again Example: pancreatic beta cells secrete insulin, are directly sensitive to blood hormone concentration, if it rises abouve 5mM, insulin is secreted until it is brought down to the right level, then it is switched off

Answer 220

Controlling hormone is a trophic hormone Secreted from anterior pituitary gland Example: Secretion of cortisol is controlled by ACTH negative feedback in some trophic hormones

Answer 221

ACTH: adrenocorticotrophic hormone, affects the adrenal gland and cortisol TSH: thyroid stimulating hormone, affects T4 secretion GH: growth hromone, affects metabolism LH: luteinising hormone, affects ovary and testis function FSH: follicle stimulating hormone, affects ovary and testis function Prolactin: affects breast development and milk production

Answer 222

Come from nerve cells in the hypothalamus Travel to anterior pituitary via the hypophyseal portal vessels Allows brain to control hormone secretion Thyrotrophin releasing hormone, TRH Corticotrophin releasing hormone, CRH Somatotrophin releasing hormone, SRH, stimulated GH release Somatostatin, inhibits GH release

Answer 223

Occurs in liver and kidney and sometimes target tissues Steroid hormones are inactivated by increasing their water solubility, can be excreted in urine or bile Protein hormones need extensive chemical changes and are degraded to amino acids which are recycled

Answer 224

Arcuate nucleus in the hypothalamus Group of neurones consisting of two types Primary neurones: sense metabolite leves in blood, respond to hormones. Secondary neurones: synthesise input from primary neurones and synthesise a response via the vagus nerve

Answer 225

Excitatory: stimulate appetite via neuropeptide Y and agouti related peptide Inhibitory: suppress appetite by releasing pro-opiomelanocortin (POMC)

Answer 226

Beta endorphin, reward system, euphoria and tiredness ACTH, stimulate cortisol Alpha melanocyte stimulating hormone: a-MSH, acts on melanocortin 4 receptors which suppress appetite

Answer 227

GHRELIN: peptide released from the wall of the empty stomach, activates stimulatory neurones in the arcuate nucleus and appetite. Stretch of stomach caused by food intake inhibits Ghrelin. LEPTIN: Peptide released by adipocytes, levels correlate to fat stores. Stimulates inhibitory and inhibits stimulatory neurones in arcuate nucleus, suppresses appetite. Lack of leptin can cause obesity. Induces expressionof UCP in mitochondria, lose heat rather than get ATP PYY: released from small intestine wall, suppressed appetite. INSULIN: same mechanism as leptin but less important. AMYLIN: peptide from B cells in pancreas, supresses appetite, decrease glucagon secretion and slow gastric emptying

Answer 228

Group of symptoms commonly found in obese peopl Insulin resistance, dyslipidaemia, glucose intolerance, hypertension Associated with central adiposity, sedentary lifestyle CVS risk factors Controversial WHO criteria: BMI above 30, blood pressure 140/90, high TAGs, HDLs low, high fasting glucose etc

Answer 229

David barker showed that rhw strongest association of adult disease like CHS, hypertension and T2DM is low birth weight. Suggests experience of foetus in utero determines future health. Biochemical adaptation by foetus according to nutrient supply in uterus, programmed in for adult life Switching on and off genes at critical times in development EPIGENETICS: stably inherited phenotype resulting from changes in chromosome without alterations in the DNA sequence, methylations and changes in histone structure, supressing transcription, targeting promotor regions.

Answer 230

Osmolality and concentration of Na+ ions monitored by OSMORECEPTORS inthe hypothalamus (supraoptic/paraventricular nuclei) If osmolality increases ADH released from posterior pituitary Increase in collecting duct permeability to water, more absorbed into blood, more concentrated urine, lower volume. Osmolality decreases

Answer 231

Polypeptides, inside storage vesicles inside cells Steroids stored as precursor cholesterol esters as lipid droplets Thyroid hormones stored outside cell in the form of protein colloid

Answer 232

A group of disorders characterised by chronic hyperglycaemia due to insulin deficiency, insulin resistance, or both A state of hyperglycaemia leading to small and large vessel damage, in which there is premature death from cardiovascular diseases

Answer 233

An inability to produce insulin due to B cell failure, autoimmune destruction in the B islet cells in the tail of the pancreas Insulin produced adequately, but insulin resistance prevents insulin working effectively, receptors don'y work properly, especially in patients with central adiposity, many free fatty acids interfere

Answer 234

Usually in the teenage years, strong seasonal variation suggesting a link with a viral infection as a trigger Likely that a genetic predisposition interacts with an environmental triggere to produce immune activation. Production of killer lymphocytes, macrophages and antibodies that attack and progressively destroy bta cells. Associated with genetic markers HLA DR3 and HLA DR4

Answer 235

Triad of symptoms Polyuria: excess urine production. Large quantities of glucose in the blood are filtered by the kidney, exceed renal threshold, so not all is reabsorbed. Has osmotic effect of drawing more water into the urine. Polydipsia: thirst and drinking a lot, due to polyuria Weight loss: as fat and proteinare metabolised because insulin is absent

Answer 236

Decreased glucose uptake into adipose and skeletal muscle Descreased storage of glucose as glycogen in the muscle and liver Increased gluconeogenesis in the liver

Answer 237

Glucose Glycosuria

Answer 238

All populations enjoying a affluent lifestyle Usually older Overweight

Answer 239

1: commonest type in the young. 2: affects large numbers of older individuals 1: characterised by progressive loss of all or most pancreatic B cells. 2: characterised by slow progressive loss of B cells bu with disorders of insulin secretion and tissue resistance 1: is rapidly fatal if not treated. 2: may be present for a long time before diagnosis 1: must be treated with insulin. 2: may not initially need treatment with insulin but all do eventually

Answer 240

Polyuria Polydipsia Blurring of vision Urogenital infections eg thrush Symptoms of inadequate energy utilisation Tiredness Weakness Lethargy Weight loss

Answer 241

May be found with relevant HLA markers and auto antibodies but without glucose or insulin abnormalities THey may then develop impaired glucose tolerance Then diabetes which may be initially diet controlled Before becoming totally insulin dependant

Answer 242

Diet and exercise Tablets Then insulin

Answer 243

Insulin resistance Insulin production falls Impaired glucose tolerance

Answer 244

When plasma glucose is less than 3mM Insulin/sulphonylurea treatment with activity, missed meal, accidental or non accidental overdose Can be fatal when blood glucose is less than 3mM as CNS and glucose dependant tissues need a constant supply Sweating, anxiety, hunger, tremor, palpitations, confusion, drowsiness, seizures, coma

Answer 245

Blood glucose is more than 10mM Symptoms: polydipsia, polyuria, weight loss, fatigue, blurred vision, dry or itchy skin, poor wound healing. Plasma proteins become glycosylated affecting their function Ketoacidosis in T1DM Hyperosmolar non-ketotic syndrome in T2DM

Answer 246

High rates of beta oxidation of fats in the liver Low insulin to anti insulin ratio Production of huge amounts of ketone bodies Acetone can be breathed out and smelt on the patient's breath Test for ketones in the urine, ketostik The H+ associated with the ketones produces a metabolic acidosis Prostration, hyperventilation, nausea, vomiting, dehydration, abdominal pain Treated with fluids to rehydrate, and insulin

Answer 247

Triad of symptoms Random venous plasma glucose concentration of more than 11.1mM Fasting plasma glucose concentration of more than 7mM Plasma glucose concentration of more than 11.1mM, 2 hours after 75g anhydrous glucose in an oral glucose tolerance test With no symptoms must have two of the tests to confirm, with an additional test on another day with a value in the diabetic range. Important to be correct: medicolegal

Answer 248

Can not be cured Insulin is used to treat Must be injected subcutaneously As is a peptide hormone that can be digested in the stomach Appropriate doses at appropriate times to mimic normal islet behaviour May need to increase insulin with infection, trauma to reduce ketoacidosis risk Frequent test for blood glucose, finger prick, BM stick and reader Need to be aware of hypoglycaemic effects Social and psychological implications Education

Answer 249

Well being Glucose control (capillary blood glucose) HbA1c vascular risk factors: BP, lipids, smoking, exercise, diet Surveillance for chronic comlications

Answer 250

Sometime managed by diet Sulphonylureas such as glicazide increase insulin release from remaining beta cells SPANK THE PANC, acts of K ATPase pumps Biguanides such as metformin increase insulin sensitivity Insulin may be needed if cells are lost

Answer 251

Produces potentially harmful products Uptake to cells of peripheral nerves, the eye and kidney does not need insulin, is determined by concentration of glucose in ECF So in hyperglycaemia ICF in these tissues increases Glucose is metabolised via aldose reductase catalysing: Glucose + NADPH + H+ to Sorbitol + NADP+ This depletes NADPH, leading to increased disulphide formation in cellular proteins altering structure and function. Accumulation of sorbitol causes osmotic damage to cells.

Answer 252

Hyperglycaemia can cause this Plasma proteins are glycosylated Leads to disturbances in function Glucose reacts with free amino groups in proteins to form stable covalent linkages Changes net charge of the protein and 3D structure

Answer 253

Glucose reacts with terminal valin of Hb to produce HbA1c, glycosylated Hb % HbA1c is a good indicator of how effective blood glucose control has been RBCs usually in circulation for 3 months %HbA1c shows the average blood glucose concentration over last 2 to 3 months Above 6.5% is undesirable. Poor control above 10% Normal value between 4 and 6%

Answer 254

Risk of stroke Risk of myocardial infarction Poor circulation to periphery: feet Intermittent claudication: muscle pain in calf Gangrene (poor blood circulation)

Answer 255

Diabetic eye disease: changes in lens due to osmotic effects of glucose (glaucoma) and possibly cataracts. Diabetic retinopathy: damage to blood vessels in the retina which can cause blindness. Blood vessels may leak and form protein exudates on retina, may rupture and bleed. New vessels may form and easily bleed Diabetic kidney disease, nephropathy: due to damage to the glomeruli, poor blood supply due to change in kidney blood vessels, or damage from urinary tract infections. Early sign is microalbuminuria, protein in urine Diabetic neuropathy: damage to peripheral nerves which directly absorb glucose, changes or loss of sensation, and also changes due to alteration in autonomic nervous system function Diabetic feet: poor blood supply, damage to nerves, increased risk of infection. Gangrene.

Answer 256

Stored in beta cell storage granules as a crystalline zinc complex in vesicles Dissolves in the plasma and circulates as a free hormone Targets liver, skeletal muscle, adipose Interacts with cell surface receptors, a dimer. Spans the membrane, alpha chains move together, fold around insulin. Moves beta chains together, active tyrosine kinase. Initiates phosphorylation cascade and GLUT 4 expression so cells can take up more glucose.

Answer 257

Alpha cells in the islets of the pancreas SIngle chain polypeptide, flexible Synthesised as a large precursor molecule which is cleaved in post translational processing from preproglucagon Takes up active conformation when it binds to receptors on the surface of the cell. G protein coupled receptor Increases cyclic AMP in cells, which activate protein kinase A which posphorylates and activates important enzymes in cells

Answer 258

Lots of rough ER Golgi Mitochondria Defined microtubule/ filament system

Answer 259

Feeding Fasting

Answer 260

ANABOLIC Affects metabolism of carbohydrates, lipids and amino acids Short term, clears absorbed nutrients from the blood following a meal Long term, effects on cell growth and division relate to its ability to stimulate protein synthesis and DNA replication

Answer 261

Increased: Glucose uptake into tissues Glycogenesis in liver and muscle Glycolysis in liver/adipose Lipogenesis and esterification of fatty acids in liver/adipose Lipoprotein lipase activity Amino acid uptake and protein synthesis Decreased: Glycogenolysis in liver and muscle Gluconeogenesis in liver Lipolysis in adipose Ketogenesis Proteolysis

Answer 262

Increased: Glycogenolysis in liver Gluconeogenesis in liver Ketogenesis in liver Lipolysis in adipose Decreased: Glycogenesis in liver

Answer 263

Large peptide 2 chains, alpha and beta 2 disulphide bridges for stability

Answer 264

mRNA translated as preproinsulin on ribosomes of RER Signal peptide removed on insertion to ER, creating proinsulin In ER, proinsulin folds, disulphide bridges form In the trans glogi packaged into storage vesicles Proteolysis in vesicles to remove C peptide forming 2 chains Secretory vesicles accumulate in cytoplasm. Margination to cell surface Released by exocytosis

Answer 265

Endogenous insulin levels As released along with the insulin Cleaved inside the storage vesicles

Answer 266

Increased glucose levels in the ECF Glucose into cell by facilitated diffusion through GLUT 2 Leads to membrane depolarisation, influx of calcium ions Triggers exocytosis of insulin

Answer 267

Exocrine and endocrine, mixed gland Fish shaped Adjacent to the duodenum Sits behind the stomach Develops embryologically as an outgrowth of the foregut Hormones produced in the Islets of Langerhans 1% endocrine tissue Islets are adjacent to capillaries

Answer 268

Insulin: B cells Glucagon: a cells Somatostatin: d cells Pancreatic polypeptide: f cells Ghrelin: new cell type

Answer 269

Zona glomerulosa: mineralocorticoids such as aldosterone Zona fasciculata: glucocoticoids such as cortisol Zona reticularis: androgens such as testosterone Salt, sugar, sex

Answer 270

Adrenaline/epinephrine

Answer 271

Stimulates the thyroid follicular cells to produce T3 and T4 Produced in the thyrotrophs of the anterior pituitary gland

Answer 272

Controls the release of cortisol Produced in the corticotrophs of the anterior pituitary

Answer 273

Important for growth of all tissues and metabolism Counteracts insulin preventing glucose uptake Stimulates IGF1 production in the liver Produced in somatotrophs

Answer 274

Initiates and maintains lactation Acts on peripheral tissues, the breast No target gland High levels, lactation and menstrual disturbance Stimulates production not release Produced in the lactotrophs Tonic inhibitory control by dopamine Minor positive control by TRH Oestrogen increases prolactin

Answer 275

Hydrophilic Hihgh affinty receptors on cell surface of zona fasiculata and reticularis. Melanocortin receptor, cAMP as secondary messenger. Leads to activation of cholesterol esterase increasing conversion of esters to free cholesterol Also stimulates other steps in cortisol synthesis

Answer 276

Stress response Increases proteolysis, lipolysis and gluconeogenesis

Answer 277

Stimulates uptake of sodium ions in the kidney in exchange for potassium ions Over secretion increases sodium and water retention causing hypertension and muscle weakness Undersecretion causes hypotension

Answer 278

Stimulate growth and development of male gential tract Development of secondary male characteristics Anabolic actions on muscle protein Produce male effects in females

Answer 279

Stimulate growth and development of female genital tractl breasts and female secondary characteristics Weakly anabolic Decrease circulating cholesterol

Answer 280

Stress response Affects availability of all substrates increasing proteolysis, lipolysis and gluconeogenesis Decreased amino acid uptake + reduced protein synthesis + more proteolysis = MORE AMINO ACIDS More hepatic gluconeogenesis + more glycogenolysis = MORE GLUCOSE More lipolysis in adipose = MORE FATTY ACIDS Decreased peripheral uptake of glucose = ANTI INSULIN Direct effects on cardiac muscle, bone and the immune system

Answer 281

Derived from cholesterol which is tetracyclic with an OH group Cortisol is a member of the C21 steroid family Differs from other steroids in terms of Number of C atoms Number of C=C double bonds Presence of functional groups Synthesised via progesterone with enzymes All are lipophilic and must be transported by plasma proteins like transcortin Other examples: vit D/calciferol, glucorticoids, mineralocorticoids, progestins, androgens, oestrogens

Answer 282

Enzyme catalysed Tyrosine to Dopa to Dopamine to Noradrenaline to Adrenaline Noradrenaline to adrenaline by methylation They are stored in vesicles in the medullary cells Catecholamines

Answer 283

Adrenaline, noradrenaline, some dopamine Modified sympathetic ganglion

Answer 284

Amine Cyclic -OH groups Secreted in response to stress Fight or flight response

Answer 285

CVS: increase cardiac output and increase muscle blood supply CNS: increase mental alertness CARBOHYDRATE METABOLISM: increase glycogenolysis in liver and muscle LIPID METABOLISM: increase lipolysis in adipose

Answer 286

Hypertension Palpitations Sweating Anxiety Pallor Glucose intolerance Usually caused by a tumour in the adrenal medulla PHAEMOCHROMOCYTOMA

Answer 287

Lipid soluble so can cross plasma membranes Binds to cytoplasmic receptor Hormone receptor complex travels to nucleus Interacts with specific regions of DNA Changes the rate of transcription of specific genes May take some time to act

Answer 288

Does not cross the cell membrane Binds to adrenoreceptor on the outside of the cell Secondary messenger affects cell activity

Answer 289

Positive hypothalamic control from CRH Secreted in response to chemical, physical and emotional stress Stimulates release of ACTH from corticotrophs in the anterior pituitary Both secreted in a pulsatile fashion Increased activity in the morning, reduced at night ACTH binds to cell surface receptors, zona fas. and ret. Activated cholesterol esterase to free cholesterol Negative feedback on both ACTH and CRH

Answer 290

ACTH is a single chain polypeptide Precursor is a large protein POMC Post translational processing of POMC makes ACTH, a-MSH and endorphins MSH sequence is inside ACTH So some MSH activity when produced in excess, eg lack of negative feedback Stimulates melanocytes to produce melanin, buccal cavity, scars, palmar creases In Addisons or ACTH related Cushings

Answer 291

Increased activity of the adrenal cortex due to a tumour, adenoma Tumour of the anterior pituitary secreting excess ACTH Excess CRH Ectopic secretion of ACTH

Answer 292

Deficiency: low glucose. Excess: High glucose D: Weight loss. E: Weight gain D: Nausea. E: Increased appetite D: Hypotension. E: Hypertension

Answer 293

Increased muscle proteolysis Hepatic gluconeogenesis Associated glucose increase in blood, polyuria and polydipsia - 'steroid diabetes' Prooximal muscle wasting, thin weak arms and legs Purple straie on lower abdomen, catabolic effects on protein in skin. Easy bruising Lipogenesis in adipose, deposition of fat in neck, abdomen and face, weight gain. Moon shaped face, cushingoid shape Increased susceptibility to bacterial infections, acne, due to immunosuppressive, anti inflammatory and anti allergenic actions of cortisol Back pain and rib collapse, osteroporosis, loss of bone matrix protein Minveralocorticoid effects, retention of sodium and water producing hypertension

Answer 294

Diseases of the adrenal cortex, such as auto immune destruction, this reduces glucocorticoids and mineralocorticoids Disorders in the pituitary or hypothalamus that lead to decreased ACTH or CRH secretion, only affects glucocorticoids

Answer 295

Measurement of plasma cortisol and ACTH MUST NOTE TIMING - circadian rhythm Breakdown products measurement: 17 hydroxysteroids 24 hour urinary excretion of cortisol

Answer 296

Acute emergency (crisis) or chronic debalitating disorder (disease) Loss of mineralocorticoids, hypotension due to sodium and fluid depletion, especially postural Insidious onset with non specific symptoms of tiredness, extreme muscular weakness, anorexia, vague abdominal pain, weight loss, dehydration and dizziness Increased pigmentation, more ACTH due to lack of negative feedback Hypoglycaemia especially on fasting, decreased cortisol so decreased catabolism Crisis can be caused by stress such as trauma, infection, leading to nausea, vomiting, extreme dehydration, hypotension, confusion, fever and even coma Clinical emergency that must be treated with IV cortisol and fluid replacement, dextrose in saline to avoid death

Answer 297

Potent synthetic steroid Normally when given orally, would suppress ACTH secretion and therefore cortisol Supression of 50% is characteristic of Cushing's, as although the diseased pituitary is relatively insensitve to cortisol it does respond somewhat to potent steroids Does not suppress adrenal tumours or ectopic ACTH production

Answer 298

Synthetic ACTH Tests for primary adrenal addisons Would usually increase plasma cortisol by more than 200ml Normal response usually excludes Addisons Tests for Addison's by stress test, give insulin to induce hypoglycaemia. ACTH should increase.

Answer 299

Steroid receptors form part of a family of nuclear DNA binding proteins that include thyroid and vit D receptors They all have 3 main regions: hydrophobic hormone binding region, DNA binding region rich in cysteine and basic AAs, a variable region Sequence homology in hormone binding region between glucocorticoids, mineralocorticoids, androgens, oestrogen, thyroid Low affinity binding to other receptors Significant when cortisol concentration is high Stimulate fluid and sodium reabsorption in kidney, hypernatraemia, hypokalaemia Stimulation of male genital tract and male characteristics, ANABOLIC

Answer 300

Insulin tolerance test Stops somatostatin GH increases if normal Glucose tolerance test Somatostatin up GH decreases if normal

Answer 301

Surgery: transcranial or transphenoidal Radiotherapy: external beam, gamma knife, protects vision but possible pituitary damage, increased stroke risk Medical: dopamine agonists reduce prolactin. Somatostatin analogues for acromegaly GH receptor analogues stimulate IGF1

Answer 302

Neuroectoderm Anti-diuretic hormone Oxytocin

Answer 303

ADH deficiency or resistance Water not reabsorbed by the kidney Polyuria and polydipsia High serum osmolality, low urine osmolality Cranial - disease of the hypothalamus or pituitary stalk

Answer 304

Visual disturbance: up growth compressing the optic chiasm Lateral Carvernous sinus invasion affects cranial nerves Secreting tumour: More GH, acromegaly, coarse features, hypertension, headaches, diabetes, gigantism if before puberty Prolactinoma: menstrual disturbance, galactorrhoea, infertility ACTH: Cushings Non secreting tumour: Posterior, no ADH, Diabetes insipidus. Anterior, low GH, LH, FSH\< TSH, ACTH, more prolactin.

Answer 305

5 Ps Pregnancy Physiological Pharmacological Pituitary: prolactinoma Polycystic ovaries

Answer 306

Produced at the top Stored at the bottom

Answer 307

Needed for skeletal growth, metabolism, muscle strength, bone density, cardiac function, quality of life Deficient: short stature, in adult cause osteopenia, more fat, less muscle Excess: acromegaly in adults, gigantism before puberty, can be abused in sport

Answer 308

Enzyme deficiency Build up of androgens Less mineralocorticoids and glucocorticoids Autosomal recessive Virilisation of female baby, clitiromegaly Neonatal salt losing crisis Hypotension, hypoglycaemia, hyponatraemia

Answer 309

Hydro/flurocortisone

Answer 310

TB Surgical removal Haemorrhage Infarction Infiltration Adrenal leukodystrophy

Answer 311

Increase steroids in incurrent illness Steroid card, medic alert bracelet Emergency 1M hydrocortisone ampoule

Answer 312

Neck Anterior to lower larynx and upper trachae Inferior to the thyroid cartilage Recurrent laryngeal and external branch of superior laryngeal nerves lie close

Answer 313

Highly vascularised, 3 arteries and veins, superior, middle and inferior 2 lateral lobes connected by a central isthmus 2 - 3 cm across, normally weighs 20g 2 major cell types: follicular and parafollicular Abundant sympathetic and parasympathetic nervous system, stimulation by them increases thyroid hormone

Answer 314

Arranged in units called follicles, seperated by connective tissue Follicles are spherical Lined by epithelial cells (follicular cells) surrounding a lumen The lumen contains protein: colloid

Answer 315

In the connective tissue around follicles C cells

Answer 316

In the follicular cells T4: Thyroxine T3: Triiodothyronine In the parafollicular/C cells Calcitonin

Answer 317

Needed to modulate metabolism Role in growth and development Needed for nervous development

Answer 318

Derived from tyrosine With addition of iodine, the number refers to the number or iodine atoms Soluble in fat

Answer 319

T4 is much more stable than T3 T4 is produced in large quantities then converted to T3 in the peripheral tissues T3 has a shorter half life

Answer 320

Transport of iodide actively into epithelial cells With 2 Na+ ions (Sodium Iodide transporter, Na/K pump creates a Na gradient) Synthesis of tyrosine rich protein THYROGLOBULIN in the epithelial cells Exocytosis of thyroglobulin into the lumen of the follicle Oxidation of iodide by peroxidase to create iodinating species iodination of side chains of tyrosine residues to produce MIT and DIT Coupling of MIT + DIT = T3 DIT + DIT = t4

Answer 321

Stored extracellularly In the lumen of the follicles As part of the thyroglobulin molecules Will last several months at the normal rate of secretion

Answer 322

Thyroglobulin taken up into epithelial cells By endocytosis Proteolytic cleavage Releases T3 and T4 Diffuse from epithelial cells Into circulation

Answer 323

99% bound to proteins Hydrophobic TBG: Thyroid Binding Globulin Pre albumin Albumin Only free hormone is active T3 lower affinity for proteins so more is free and a shorter half life

Answer 324

T3: 2 days T4: 8 days

Answer 325

Hypthalamic and anterior pituitary control TRH: tri peptide from dorsomedial nucleus of hypothalamus. Stress and decrease in temp increase secretion Travels via hypophyseal portal system to anterior pituitary to stimulate TSH from thyrotrophs TSH in blood to follicular cells Negative feedback from thyroid hormones

Answer 326

Glycoprotein consisting of 2 non covalently linked subunits, alpha and beta Released in low amplitude pulses Circadian rhythm Interacts with surface receptors Stimulates synthesis and secretion of T3 and T4 Trophic effects increasing vascularity, size and number of follicular cells Trophic effect can cause goitre which can be over or underactive

Answer 327

Increase metabolic rate Increased uptake of glucose and metabolism of it Stimulate mobilisation and oxidation of fatty acids Stimulate protein metabolism Mainly catabolic so highger BMR, increased heat UCPs, increased o2 consumption Response can occur slowly

Answer 328

Bone mineralisation Increase heart muscle protein synthesis CNS development: cellualr processes of nerve cells hyperplasia of cortical neurones, myelination Indirect hormone and neurotransmitter interaction: stimulate receptor synthesis Tachycardia in heart muscle. Increased motility in GI tract Permissive role in FSH and LH actions, ovulation fails in absence Turnover of proteins and glycoproteins in skin and hair and nails

Answer 329

Absence of thyroid hormone from birth, hypo Severe physical and mental retardation Lack of CNS development Coarse features, diminished linear growth, delayed sexual development Must be corrected in a few weeks to reverse, all newborns are tested with T4/TSH assays Hypo in adults"poor concentration, memory, lack of initiative

Answer 330

Cross plasma membrane Interact with high affinity receptors in the nucleus or possibly mitochondria Binding of T3 to hormone binding domain Unmasks DNA binding domain Interaction of hormone receptor complex with DNA Increases rate of transcription of specific genes that are translated into proteins Stimulates oxidative energy metabolism

Answer 331

Removal of the 5' iodide Helps to regulate the amount of free hormone in the cells as T3 is 10x more active than T4 Removal of 3' iodide produces rT3 which is inactive

Answer 332

Hashimotos: autoimmun destruction of follicles or production of an antibody that blocks the TSH receptor on follicular cells Post surgery Radioactive iodine Anti thyroid drugs Secondary: lack of TSH Congenital Iodine deficiency Treated with oral thyroxine T4, measure TSH levels to stabilise.

Answer 333

Weight gain Brady cardia Cold intolerance Dry and flaky skin Alopecia Tiredness Deep husky voice due to goitre, trophic effect of more TSH Neuromuscular: weakness, muscle cramps and cerebella ataxia (clumsiness) Poor concentration/memory loss Constipation

Answer 334

Grave's disease: autoimmune, antibodies are produced which stimulate TSH receptors on follicle cells, resulting in increased T3 and T4 secretion Toxic overproducing T3/4, multinodular goitre Exessive T3/4 therapy THyroid carcinoma, but 99% don't cause hypo/hyperthyroidism Ectopic thyroid tissue

Answer 335

Carbimazole Inhibits the addition of iodine into thyroglobulin

Answer 336

Heat intolerance Weight loss Tachycardia Physical and mental hyperactivity Intestinal hyperactivity Increase appetite Exopthalmos Skeletal and cardiac myopathy, causing tiredness, weakness, breathlessness Osteoporosis due to increased bone turnover and preferential reabsorption Hyperreflexive Increased perspiration

Answer 337

Carbimazole for graves Thyroidectomy, complete or partial Radioactive iodine Then manage hypo Important to be aware of parathyroids

Answer 338

BMR and catabolic activity: Hyper: increase. Hypo: Decrease Sympathetic and CNS activity, GI tract, CNA: Hyper: increase. Hypo: Decrease Direct effect on tissues: Hyper: CVS. Hypo: CVS, subcutaneous

Answer 339

Euthyroid: Normal free T4, Normal TSH Hypothyroid: Low free T4, high TSH Hyperthyroid: High free T4, low TSH

Answer 340

Large variation in the population Small variation in the inividual

Answer 341

In pregnance More oestrogen, more TBG synthesis Fall in free T3/4 Removes negative inhibitory feedback More TRH and TSH, so more T3 and T4 Free T3 and T4 back to normal Total amount of thyroid hormones in the blood increases

Answer 342

T3 and T4 are degraded by removal of iodine Liver and kidney

Answer 343

More females than males 1-2% of women

Answer 344

Hormone secretion Nerve conduction Inactivation/activation of enzymes Muscle contraction Exocytosis intracellular secondary messenger

Answer 345

Calcium ions between 1.0 to 1.3 mM

Answer 346

Free ionised species Bound to proteins such as albumin Complexed with organic anions like citrate and oxaloate

Answer 347

Part of adenosine triphosphate molecule Crucial role in cellular energy metabolism Activation and inactivation of enzymes Not strictly regulated Fluctuates during the day, e.g. after meals

Answer 348

Both are major components of calcium hydroxyapatit crystals which mineralise bone They are regulated by the same hormones, parathyroid horomones, 1,25-dihydroxyvitaminD/calcitriol, and to a lesser extent calcitonin These hormones act on bone, the kidneys, the GI tract to control levels of these ions in plasma Differing effects on levels of each ion

Answer 349

Parathyroid hormone Calcitriol They both raise serum calcium concentrations, but by different mechanisms and time scales

Answer 350

In animals lowers serum calcium In humans suggested to only preserve the maternal skeleton Lowers serum calcium Increase osteoclast activity

Answer 351

Bone: act on calcium hydroxyapatite store within collagen fibrils Kidneys: filter, reabsorbed, most in PCT, then loop of Henle, hormonal control in DCT Gut: in through diet and egest through faeces, taken up in duodenum and jejunum, secretions are rich in calciu. Energy dependant uptake

Answer 352

Parathyroid hormone, PTH Polypeptide hormone Secreted from the parathyroid glands, typiaclly 2 pairs, by CHIEF CELLS

Answer 353

Changes in calcium ion concentration alter PTH by negative feedback Chief cells have unique G protein calcium receptors on the cell surface Increased calcium binding to G protein binding receptors stimulates Phospholipase C inhibiting adenylate cyclase This leads to reduced cAMP and reduced PTH release Reverse occurs when calcium is low

Answer 354

Bone: osteolysis within 1 to 2 hours. Osteoblast synthesis. Cytokines secreted which expose the bone surface. Decrease osteoblast activity, which usualy protect bony surface. Protect osteoclasts from apoptosis. Reabsorption of mineralised bone, release of Pi and calcium into ECF Kidney: Affects tubular cells. In DCT, increases calcium ion reabsorption, therefore decreasing excretion. Supresses reabsorption of Pi, which prevents calcium stone formation. Gut: stimulates conversion of vitamin D to active form. Increased uptake of caclium from the cut, less egested.

Answer 355

Long term action Increase calcium and Pi absorption in gut, active uptake Mobilise calcium stores in bone Stimulate reabsorption in the kidney

Answer 356

Vitamin D is formed in the skin or absorbed in the gut from the diet Has a short half life So is converted to calciferol (25-hydroxyvitamin D) in the liver, which has a 2 week half life Vitamin D is not regulated Final conversion is in the kidney to calcitriol, regulated by PTH Hydroxylation of C1

Answer 357

Transcriptional and post transcriptional level Low serum calcium up regulates transcription and prolongs mRNA survival High serum calcium down regulates transcription Contrinually synthesised but little store Chief cells degrade and synthesise Increased PTH cleavage in cheif cells, increased by high serum calcium Released PTH cleaved in liver Negative feedback

Answer 358

Two forms vitamin D2 (gut) and D3 (sunlight) both form calcitriol and are equipotent Needs 2 hydroxylations In liver at c25, not regulated In kidney at C1, regulated by PTH

Answer 359

PTH affects tubular cells in the kidney Increase calcium reabsorption in the DCT Pi is removed from circulation by inhibition of reabsorption in PCT Prevents calcium stone formation

Answer 360

Decrease in plasma calcium Leads to parathesia - tingling Tetany: involuntary muscular contraction Paralysis, even convulsions Due to low amount of calcium bound to the NMJ membrane, allowing Na+ to depolarise it much more easily, lowers threshold More PTH, can cause rickets

Answer 361

High serum calcium levels MOANS GROANS AND STONES May result in formation of kidney stones, renal calculi Constipation Dehydration (treat with fluids lost in urine) Kidney damage Tiredness and depression Could be primary hyperparathyroidism, remove benign tumour

Answer 362

Accidental surgical removal Life threatening hypocalcaemia

Answer 363

Breast/ prostate/ sometimes myeloma etc Parathyroid hormone related peptide (PTHrp) is a peptide hormone produced by these Leads to humeralhypercalcaemia of malignancy Similar structure to PTH Increased calcium release from bone, less calcium excreted, less phosphate reabsorption Does not increase C1 hydroxylasse activity in the kidney so does not increase calcitriol concentration

Answer 364

8kg As the mother has to supply everything required for the growth of the foetus: nutrients, vitamins, minerals, oxygen and water

Answer 365

Mainly diffusion, facilitated diffusion Placental exchange Some active transport

Answer 366

Preparatory increase in maternal nutrient stores Especially adipose Bigger apetite Ready for more rapid growth of foetus, birth and lactation Increasing levels of insulin promote anabolism Increased beta cell glucose sensitivity, hyperplasia and hypertrophy More glycogen Increased insulin action on storage tissues Less insulin action on energy using tissues

Answer 367

Maternal insulin: concentration in maternal circulation increases. Acts to promote the uptake and storage of nutrients, largely as fat in adipose Foetal-placental hormones: more imporant as pregnancy processd Largely oppose the actions of insulin: anti-insulin Maintain the glucose gradient to ensure it is in constant supply

Answer 368

Adjust maternal blood concentrations Modify nutrient stores to cope with demands, highest in late pregnancy and lactation Minimal disturbance to maternal homeostasis Fat stores accumulate in first half Increase in blood volume Placenta supersedes HPA axis

Answer 369

Marked increased in growth of the placenta and foetus Adapts to increased demand Foetal placental demands are met by keep concentration of nutrients high (glucose above 5mM) in maternal circulation by: Reduce maternal utilisation of glucose, switch to fatty acids Delay maternal disposal of nutrients after meals Relase FAs from stores Maternal levels of insulin still increase, but anti insulins at a faster rate (oestrogen, progesterone, human placental lactogen)

Answer 370

Marked decrease in insulin to anti insulin ratio More fatty acids to the liver Ketone bodies fuel for the fetal brain

Answer 371

B cells in the endocrine pancreas unable to response to the metabolic demand of pregnancy Fails to release the amount of insulin required loss of control of metabolim, blood glucose increases, diabetes results Consequences: effects of hyperglycaemia, excess fetal growth, macrosomia, fat baby with lots of liver and muscle glycogen, difficult delivery Usually corrects after birth Women may be more likely to develop type 2 diabetes later in life Treat with insulin short term if severe

Answer 372

Energy demands of cardiac and skeletal muscle are met by fuel mobilisation from stores Minimal disturbances to homeostasis keep rate of mobilisation equal to rate of utilisation Glucose supply to brain is maintained, prevent hypoglycaemia Waste products removed as quickly as possible Oxygen supply maintained Adaptations to temperature, CVS and resp. system

Answer 373

Type of exercise, muscles used Intensity and duration of exercise Physical and nutritional status of individual

Answer 374

ATP needed to detach myosin from actin in muscle contraction Energy from hydrolysis ADP must be converted back by coupling to oxidation of fuel molecules Glycogen and TAGs

Answer 375

Aerobic, last for long periods, 1 hr Anaerobic, very quick, 2 mins Liver helps to prevent hypoglycaemia and keep up CNS Muscle advantageous as availability not affected by blood supply, no need for membrane transport into muscle cells, G 6 P produced without ATP Can't produce glucose as no G 6 P phosphatase

Answer 376

Build up of lactate and H+ H+ exceeds buffering capacity Produces fatigue as function is impaired Inhibits glycolysis by H+ H+ interferes with actin and myosin H+ causes sarcoplasmic reticulum to bind calcium which inhibits contraction

Answer 377

Rate of fatty acid release, lipolysis Limited carrying capacity in blood: albumin Raate of fatty acid uptake into cells and mitochondria, cartinine shuttle in B oxidation More oxygen needed per mole to metabolise FAs than glucose Can only be metabolised aerobically

Answer 378

Insulin needed to express GLUT4 channels to take up glucose Glucagon stimulates glycogenolysis in lover Adrenaline causes glycogenolysis in muscle

Answer 379

Body composition changes: more muscle, less adipose Glucose tolerance improves, muscle glycogenesis increases More GLUT 4 channels Insulin sensitivity of muscles increases Blood lipids decrease, VLDL and LDL down, HDL up Blood pressure falls Psych effects: well being

Answer 380

Skeletal muscle changes: More and bigger fibres More GLUT4 More capillaries Better B oxidation capacity, more mitochondria More myoglobin More glycogen storage CVS changes: Lower heart rate for same output Hypertrophy of let ventricle Lower BPM More 2,3-BPG in blood, lowers Hb affinity

Answer 381

Confined to skeletal muscle that works anaerobically Controlled by nervous system, noradrenaline, with some input endocrine, adrenaline Muscle ATP and creatine phosphate used first Muscle glycogen mobilised to provide G 6 P G 6 P mobilised via glycolysis Anaerobic glycolysis oxygen supply inadequate Produces lactate and H+, acidotic effecct, cramp as H+ stimulate nerve ends

Answer 382

Regenerates ATP 60% aerobic, 40% anaerobic metabolism of glycogen Must eliminate lots of CO2 but no major problem with H+, can be buffered Initial sprint: ATP and C P used, anaerobic glycogenolysis Long middle phase, ATP aerobically from glycogen in muscle, some lipolysis Finishing burst with anaerobic glycogenolysis producing lactate

Answer 383

Carbohydrate stores insufficient to complete distance so fatty acids must be oxidised by muscle cells Mostly aerobic, use all fuel types Muscle glycogen used in a few mins Glucose from liver glycogen Gluconeogenesis FA beta oxidation Control is mainly hormonal: insulin levels fall. Adrenaline noradrenaline and growth hormone rise rapidly to promote lipolysis. Cortisol and glucagon levels rise gradually, mobilise fats and gluconeogenesis

Metabolism Flashcards

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