Nutrition (IAS8-18) Flashcards
(154 cards)
1
Q
What are the types of micronutrient
A
Vitamins , minerals
2
Q
Is ethanol a micronutrient or macronutrient?
A
micronutrient
3
Q
what is essential nutrient
A
cannot be synthesized in body or deficient in body, must be obtained in diet
4
Q
ESSENTIAL AMINO ACIDS
A
Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Leucine and Lysine (PVT TIM HALL)
5
Q
Total daily energy expenditure composition?
A
Basal metabolic rate + thermic effect of food + energy expenditure during physical activity
6
Q
Essential fatty acids?
which is omega-3, which is omega-6?
A
a-linolenic acid (omega-3) , linoleic acid (omega-6)
7
Q
Factors affecting BMR (check 鷄精ppt for quick look if no time)
A
Gender (Male > Female)
Age (Child > Adult)
Child > Adult
Health
( * Elevated by fever
* Elevated in individuals with hyperthyroidism (e.g.
Graves disease)
* Low in individuals with hypothyroidism (e.g.
Hashimoto’s disease)
* Elevated during pregnancy and lactation)
Hormones
( * Elevated by high levels of thyroid hormones (e.g., thyroxine), growth hormones, sex hormones,
epinephrine, and cortisol)
8
Q
WHAT is basal metabolic rate? How many percent of total daily energy expenditure?
A
energy expenditure to maintain normal physiological functions, 60-70%
9
Q
What is thermic effect of food? Percentage of physical exercise in total daily energy expenditure?
A
Energy used to digest, absorb and metabolize food, physical exercise: 10%
10
Q
How many kcal/g for carbs, proteins, lipids?
A
4,4,9 respectively
11
Q
3 types of fat? Where are they found?
A
Visceral (around abdomen), ectopic (around heart and pharynx), subcutaneous (under skin)
12
Q
4 reference standards of dietary reference intake levels (DRIs) - what are they and define them
A
- Estimated Average Requirement (EAR): Level estimated to meet the requirement of 50% of the healthy individuals in a particular life stage and gender group.
- Recommended Dietary Allowance (RDA): Level of nutrient intake to meet the requirements of nearly all (97–98%) individuals in a life stage and gender group.
- Adequate Intake (AI): If EAR or RDA not available, estimates of nutrient intake by a group of (or groups of) apparently healthy people that are assumed to be adequate.
- Tolerable Upper Intake Level (UL): Highest level of nutrient intake likely to pose no risk of adverse health effects for almost all individuals in a particular life stage and gender group.
13
Q
Fat soluble vitamins, their method of transport and absorption method?
A
ADEK, transported by carrier proteins/receptors, absorbed by lymph
14
Q
Water soluble vitamins, their method of transport and absorption method?
A
B complex, C, transported freely in body (B12 needs carrier proteins), absorbed into blood
15
Q
Vitamin ADEK functions, source, deficiency, excess?
A
CHECK 鷄精 ppt p17 (original file without mods)
16
Q
Vitamin D - most common form in blood?
A
Cholecalciferol
17
Q
Vitamin D conversion cycle?
A
7-dehydrocholesterol in skin > Cholecalciferol (UV light) >
Cholecalciferol, Ergocalciferol from diet >
Cholecalciferol, ergocalciferol in blood >
Liver: Cholecalciferol to 25-OH-D3, ergocalciferol to 25-OH-D2 >
Kidney: 25-OH-D3 to 1,25-OH2-D3, 25-OH-D2 to 1,25-OH2-D2
18
Q
Function of 1,25-OH2-Vitamin D?
A
Calcium mobilization from bones, renal reabsorption of calcium, intestinal reabsorption of calcium, causes increase in blood plasma calcium levels
19
Q
Vitamin K conversion from what form in diet to what active form in body? Function of the active form?
A
phylloquinone (form in diet) > hydroquinone (active form) > epoxide after gamma-carboxylation
Facilitates gamma carboxylation of glutamate residue to carboxylated protein (clotting factor)
20
Q
What does warfarin do to vitamin K?
A
inhibit phylloquinone>hydroquinone AND epoxide>hydroquinone
SO prevents blood clotting (gamma-carboxylation) as Vitamin K cannot act as cofactor
21
Q
Types of Vitamin B
A
B1, B2, B3, B5, B6, B7, B9, B12
22
Q
Vitamin B names??
A
B1: thiamine
B2: riboflavin
B3: niacin
B5: pantothenic acid
B6: pyridoxine
B7: biotin
B9: folic acid
B12: cobalamin
23
Q
All vitamin Bs that act as coenzymes? for what processes?
All vitamin Bs that act as electron transporters?
A
Coenzymes: B1 (carbohydrate metabolism), B5 (component of coenzyme A), B6 (amino acid metabolism), B7 (fat, glycogen, amino acid synthesis), B9 (Receives 1C from donors, eg Ser/Gly/His and transfers to intermediate to synthesize nucleic acid, amino acid metabolism),
B12 (Homocysteine → methionine, Methylmalonyl coA → succinyl coA) (MUST REMEMBER)
Electron transporters: B2, B3
24
Q
Name all Energy-releasing Vitamin B-complex
A
Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic acid (B5), Biotin (B7)
25
Name all Haematopoeitic Vitamin B-complex - deficiency consequences?
Folic acid (B9), Cobalamin (B12)
Deficiency (applies for both of them) causes megaloblastic anemia (blood stem cells cannot divide and become enlarged)
as B12 needed to activate B9 into tetrahydrofolate (active form) for cell division
B9 deficiency: neural tube defect (spina bifida, anencephaly)
26
How does folate deficiency cause megaloblastic anemia
Tetrahydrofolates needed in metabolic pathway to produce TMP and folate derivatives needed as enzyme cofactors to make purines
Cells cannot make DNA and cannot divide
27
What will happen in patients with folate deficiency?
folate deficiency can result in megaglobastic anaemia cauase by diminished synthesis of purines and TMP (without them, cells are unable to make DNA and thus unable to divide)
28
How do B9 and B12 help in cell division
B9: Make TMP and Purine
B12: activate B9 into tetrahydrofolate (active form)
29
Vitamin C function?
Maintains structural integrity of collagen
Keeps Fe2+ reduced so that prolyl 4 hydroxylase is functional to produce hydroxyproline (for collagen folding)
30
By daily required amount how to classify micro and macronutrients
Macro: >100mg
Micro: <100mg
31
Check the ppt for lists of mineral deficiencies BUT effects of:
1) Hypo and hypernatremia?
2)Hypo and hyperkalemia?
3)Hypo and hypercalcemia?
4) iron excess/deficiency?
1) Hypo: cerebral edema, hyper: dehydration, cannot restore blood osmotic balance
2) arrhythmia BUT different causes
hypo: too little K+ so difficult to repolarize cardiac muscles (ventricular repolarization delayed)
hyper: too much K+ so difficult to trigger another excitation-contraction cycle (less Na+ pumps available as excess K+ inhibits Na+ channel proteins and lowers their availability to be used)
3)Hypo: osteoporosis, arrhythmia (calcium needed to bind to troponin and expose myosin head for contraction
hyper: kidney stones (calcium precipitate in kidney tubule)
4) excess: haemochromatosis, iron accumulate in heart/liver/pancreas, heart failure, liver cirrhosis, liver cancer etc
deficiency: iron-deficient anemia (cannot produce hemoglobin)
32
Regulation of iron in body? Function of hepcidin and ferroportin?
High [iron] in blood → increased hepcidin → decreased ferroportin and iron absorption
*
Low [iron] in blood→ decreased hepcidin → increased ferroportin and iron absorption
*Explanation
* Hepcidin is a hormone released by the liver upon detecting changes in the blood iron level. The
function of hepcidin is to inhibit ferroportin (a cellular protein) and inhibit iron absorption
from the gut
* Ferroportin is a cellular protein that can break down cellular iron stores in a protein called
ferritin and act as a transporter to release Fe2+ out
33
Which hormones regulate calcium and phosphate levels in blood
calcitriol (1,25-OH2-D3), parathyroid hormone, calcitonin
34
Functions of calcitriol, calcitonin, parathyroid hormone??? WHERE are they produced?
calcitriol, PTH: increase blood calcium and phosphate levels (mobilize ca2+, phosphate from bones, increase gut absorption)
calcitonin: decrease blood calcium level (secreted by thyroid gland)
increase calcium and phosphate deposition in bone, calcium excretion from kidneys
35
define enzyme
Enzymes are protein catalysts that speed up
biochemical reactions without themselves being
changed
36
Working principle of an enzyme
Enzymes speeds up the reaction rate of a biochemical reaction by LOWERING the ACTIVATION ENERGY BARRIER
37
define oxireductases and give two examples.
They are enzymes that catalyse the transfer of hydrogen and oxygen atoms or electrons from one substrate to another
Examples: Dehydrogenase, Oxidase
38
define transferases and give an example
They are enzymes that catalyse the transfer of a specific group (e.g. phosphate, methyl) from one substrate to another
Example: kinase
39
define hydrolases and give some examples
They are enzymes that catalyse the hydrolysis of a substrate to form two products
Example: Esterase, Lipase, Amylase
40
define isomerases and give some examples
They are enzymes that catalyse the alteration of the molecular form of the substrate
Example: Isomerase, mutase
41
define lyases and give some examples
They are enzymes that catalyse the non-hydrolytic removal or addition of a group
to a substrate
Example: Decarboxylase
42
define ligases and give some examples
They are enzymes that catalyse the joining of two molecules with the formation of new bonds and the simultaneous breakdown of ATP
Example: DNA ligase, synthtase
43
how much faster can a reaction proceed with the presence of an enzyme
Enzyme catalysed reactions are 10^3 to 10^17 times faster that uncatalysed reactions
44
name and define the two types of metabolism
anabolism (divergent, energy-consuming): set of metabolic pathwats that synthesise larger molecules from smaller ones
catabolism (convergent, energy-releasing): set of metabolic pathways that break larger molecules into smaller ones
45
Where do the enzymatic reactions occur?
The enzyme forms an
enzyme-substrate
complex with the subtrate in the active site
46
define the active site
The active site is usually a cleft or crevice in the enzyme formed by one or more regions of the polypeptide chain
47
the backbone of the polypeptide chain in the active site will transform the ubtrates into products, true or false.
False, The functional groups from the
polypeptide chain in the active site will transform the substrates to products.
48
Do the adjacent amino acid residues constructing the active site be necessarily next to each other in the unfold polypeptide chain.
No, adjacent amino acide residues the active site of the enzyme protein need not to be next to each other.
49
What are the significances of the substrate binding site's three-dimensional structure
1. Specificity of substrate binding depends on three-dimensional arrangement of amino acids in the active site forming the substrate binding site
2. The arrangement also orientates the substrate in the correct position for catalysis by
the enzyme
50
Name the two models of enzyme-substrate interaction
Induced-fit model
(The substrate binding site is not
a rigid pocket, but a dynamic surface with
flexible 3-D structure. As the substrate binds, the side chains of the amino acids in the
active site will reposition to interact with the substrate for the reaction to occur)
Lock-and-Key model
(The amino acid residues of the substrate binding site are arranged in a complementary 3-D surface that recognizes the
substrate)
51
Consider the Lock-and-Key model, how are substrates bound onto the specific active sites?
The substrate is bound via hydrophobic interactions, electrostatic interactions and
hydrogen bonds
52
Name one of the largest induced fits known
Glucose binding of hexokinase
(*With the binding of glucose, the active site cleft of hexokinase
closes)
53
What does Michaelis-Menten equation describe?
Michaelis-Menten equation describes the relationship of the enzyme rate (vi) to the
substrate concentration [S] and 2 parameters Km and Vmax
54
Define Vmax
Vmax is the maximal velocity
achieved at infinite amount of
substrate
55
define Km
Km is the concentration of
substrate needed to achieve
half of Vmax
56
What does Km measure?
Km also measures the affinity the enzyme has for a substrate
57
Describe the relationship between the value of Km and the affinity of an enzyme for its specific substrates
- A low Km means a high affinity between enzyme and substrate
OR
- A high Km means is a low affinity between enzyme and substrate
58
Define Bisubstrate enzymatic reactions
Bisubstrate reactions are the most common type of enzymatic reactions involving two substrates and giving two products
E+𝐴𝑋+𝐵 ⇌ E+𝐴+𝐵𝑋
(E=enzyme)
59
Name the two types of bisubstrate enzymatic reactions
Sequential/ Single displacement (ordered and random) reactions and double displacement reactions (or Ping Pong reactions)
60
describe the charateristics of an ordered single displacement reaction
1. The first substrate S1 binds to the active site of the specific enzyme before the second substrate S2
2. The enzyme remains chemically unchanged
61
describe the characteristics of a random single displacement reaction
1. The binding sequence of S1 and S2 does not affect the process of the enzymatic reaction
2. The enzyme remains chemically unchanged
62
Describe the process of a double-displacement enzymatic reaction
1. S1 binds onto the substrate-binding site of enzyme first
2. The enzyme catalyses the convertion of S1 into a product, with a functional group bounded into the enzyme
3. S2 binds onto the substrate-binding site of the enzyme, reacting with the functional group to form a product
4. Enzyme remains chemically unchanged
63
Name the four factors affecting enzyme catalysis
1. Substrate conc.
2. enzyme conc.
3. pH
4. Temperature
64
How is the graph of rate of reaction against substrate conc. different from that of against enzyme conc.?
Initially, an increase in substrate concentration leads to an increase in the rate of an enzyme-catalyzed reaction. As the enzyme molecules become saturated with substrate, this increase in reaction rate levels off.
The rate of an enzyme-catalyzed reaction increases with an increase in the concentration of an enzyme.
65
Why does the changes in pH values (shifting away from optimum pH) result in the loss of activity or even denaturation?
There is an optimum pH range where the
enzymes are most active.
Changes in pH can change the ionization of functional groups in the active site resulting in the loss of activity or even denaturation
66
Why can extreme temperatures result in the low activity or even denaturation?
The extremely high temperatures cuase the active site to lose its shap, causing the enzyme to lose its ability to catalyse the reaction.
Low emperatures can lead to the low kinetic energy of both the enzyme and substrates, thus fewer number effective collisions can be achieved, leading to few enzyme-substrate complexes formed. This leads to low activity
67
define regulatory enzymes
At least one enzyme in a metabolic pathway will be regulated to control the rate of the metabolic pathway, these enzymes are called regulatory enzymes
68
3 Types of Regulation of Enzyme Activity
1. Compounds that bind reversibly to the active site
2. Changing the conformation of the active site
3. Changing the concentration of the enzyme
69
define inhibitors
define reversible inhibitors
Compounds that decreases the rate of
reaction by binding to an enzyme are called
inhibitors
If the compound is not covalently bound to the
enzyme and can dissociate at a significant
rate, it is known as a reversible inhibitor
70
three types of reversible inhibitors
1. Competitive
2. Noncompetitive
3. Uncompetitive
71
characteristics of competitive inhibitors
1. Competes with the substrate for binding at the substrate-binding site
2. Usually structurally similar to the substrate
3. Increase in substrate concentration to a sufficiently high level can overcome competitive inhibition
72
Why can the increase in substrate concentration to a sufficiently high level can overcome competitive inhibition
the increasing substrate conc. will continuously reduce the availability for an inhibitor to bind, and, thus, outcompete the inhibitor in binding to the enzyme.
73
why a competitive inhibitor to an enzyme increases Km but doesn't change Vmax
The Vmax is the maximum theoretical rate at which the reaction can proceed and is achieved when the enzyme is saturated with the substrate.
When you have a competitive reversible inhibitor, this competes directly with the substrate for the active site. Therefore if you keep increasing the substrate concentration, the substrate will outcompete the competitive inhibitor and the Vmax can be achieved. But since you have to use a much higher concentration to achieve the same rate of reaction, the Km increases.
74
characteristics of noncompetitive inhibitors
1. Does not compete with the substrate for the substrate-binding site
2. Does not affect the binding of the substrate
3. Increase in concentration of the substrate will not overcome the inhibition
75
Why do products act as reversible inhibitors and what is the importance?
1. All products are reversible inhibitors of the
enzymes that produce them
2. The decrease in the rate of the enzyme caused by the accumulation of its own product is important
Importance: It prevents one enzyme in the sequence of reactions from making a product faster than it can be use by the next enzyme
76
4 Regulation methods of the activity of rate-limiting enzymes (through conformation
changes)
⎼ Allosteric activation and inhibition
⎼ Covalent modifications
⎼ Protein-protein interactions
⎼ Proteolytic cleavage
77
define Allosteric activation and inhibition
Allosteric site is a site away from the substrate binding site. When another compound binds to it, it causes change in shape in the substrate binding site and allow /prevent substrate binding.
78
Advantages of regulation with
allosteric effectors
1. Allosteric inhibitors have a much stronger effect on the enzyme velocity than inhibitors in the active site
2. Some effectors can be activators as they do not bind the active site
3. Allosteric effectors can be molecules other that the substrate or the product of the enzyme 4. The effect of the allosteric effector is rapid
79
Conformational changes via covalent
modification
Phosphorylation
1. The activity of many enzymes are regulated
by the addition or removal of a phosphate
group on specific serine, threonine or tyrosine residues
2. The phosphate group will cause conformational changes at the catalytic site by changes in the ionic interactions or hydrogen bond patterns
80
conditions and Enzymes used in phosphorylation
phosphorylation: ATP and protein kinase
dephosphorylation: water and protein phosporylase
81
Muscle Glycogen Phosphorylase
Can be activated by either phosphorylation
or binding of AMP at the allosteric site
82
Proteolytic cleavage
Some enzymes are synthesized as proenzymes and need to undergo proteolytic cleavage to become fully functional
83
Proteolytic cleavage is irreversible, true or false?
TRUEEEE
84
example of Proteolytic cleavage and its importance
regulatory control of blood clotting:
1. Most proteases involved in blood clotting circulate in blood in the inactive form
2. They are cleaved to the active form by other proteases activated by their attachment to the site of injury
Importance: This leads to the clots forming only at the site of injury and not randomly in circulation
85
Why are nutrients important in terms of ATP production?
⎼ Catabolised to feed into the reactions leading to ATP synthesis
⎼ Some nutrients form the structural components of proteins driving the ATP
synthesis reactions
86
Why is oxygen important in term of ATP production?
Oxygen sits at the final stage of electron transport chain
X oxygen,
X ATP produced,
X cell functioning
87
Glucose overview? structures and bonds?
Cellulose made of beta glucose, beta-1,4 glycosidic linkages, linear
Starch (amylose, amylopectin)
amylose: a-glucose, alpha-1,4 glycosidic linkages, linear
amylopectin: a-glucose, alpha 1,4 glycosidic linkages with less than 10% alpha-1,6 branches, branched
glycogen: alpha 1,4 glycosidic linkages, >10% alpha-1,6 branches, branched
88
Why can't humans digest cellulose
No enzymes to break beat-1,4 glycosidic bonds
89
Digestion and absorption of sugars?
Ingestion: starch, cellulose, sucrose, lactose
Mouth: action of salivary a-amylase digestion,
starch > starch dextrins, maltose, isomaltose, maltotriose,
sucrose, lactose, cellulose
cellulose goes to colon undigested and egested
Small intestine: action of pancreatic a-amylase AND mucosal-bound enzymes (sucrase, trehalase, maltase, isomaltase, lactase)
starch, starch dextrins (under effect of amylase) > isomaltose, maltose, maltotriose
surose, lactose
Under effect of mucosal enzymes:
maltose/isomaltose/maltotriose > glucose
sucrose > glucose + fructose
lactose> glucose + galactose
glucose, fructose, galactose transported by portal circulation to liver and then other body parts
90
Transport of monosaccharides in absorptive cells of small intestine? Which transporters used for what sugars and where?
How does secondary active transport work here?
Glucose and galactose: SGLT 1 (apical side), GLUT 2 (basal side)
Fructose: GLUT 5 (apical side), GLUT 2 and GLUT 5 (basal side)
SGLT 1 cooperates with sodium potassium ATPase pump in basal side, Na+/K+ ATPase pump actively transports 3 Na+ out of absorptive cell through basal side (concentration gradient for
91
What types of glucose transporters are there + Where are the different types of glucose transporters found in the body?
Which type of transporter is insulin dependent?
GLUT 1,2,3,4
GLUT 1: BBB (RBCs, Blood-brain barrier (brain), fetal cells)
GLUT 2: Last known position is: (Liver, kidneys, pancreas, intestine)
GLUT 3: No Place (neurons, placenta)
GLUT 4: Muscle's fat (Muscle, fat cells (adipocytes)
GLUT 4
92
Fates of glucose in cells after absorption? State their pathways
How do galactose and fructose fit into these 2 pathways
1) conversion to glycogen: glucose > G6P > G1P (reverse reaction possible from G1P to G6P) > glycogen
2) glucose > G6P >pyruvate
Galactose: can be converted to G1P or galactose directly (ALL STARTS WITH G)
Fructose: can be converted to pyruvate
93
How does glucose fit into ADIPOSE STORAGE OF LIPIDS (Adipose storage of glucose)
Glucose > G3P (the backbone for triglycerides)
Then combine with free fatty acids to form triacylglycerides IN ADIPOSE TISSUE
94
The in-depth process of glycolysis?
Glucose > G6P > Fructose-6P (can reverse from F6P back to G6P) > Fructose -1,6 bisP > Pyruvate
Other substances used: Glucose > G6P: hexokinase + 1 ATP
F6P to Fructose-1,6 bisP: Phosphofructokinase-1 + 1ATP
Fructose-1,6-bisP > pyruvate: Requires 2 NAD
Produces 2 NADH, 4 ATP
95
The purpose of Pentose phosphate pathway?
Protect the body against oxidative stress, eg by neutralizing harmful peroxides (H2O2 to water)
96
Basic mechanism of Pentose phosphate pathway? What products formed? The functions of products?
Glutathione oxidized and reduced, ribose-5-phosphate and NADPH formed
ribose-5-phosphate used to make nucleotides, NADPH used as biological reductants
97
Lactose intolerance symptoms and reasons?
Gas in intestine, diarrhea, caused by deficient lactase in body
98
Classes of lipids - what type?
Bile salts, eicosanoids, steroid hormones, triacylglycerols, phospholipids, fat soluble vitamins, cholesterols
BESTPVC (acronym)
99
What fatty acids are eicosanoids mostly derived from
arachidonic acid
100
How to name omega fatty acids?
Form of X:Y w Z (w just for representing the omega sign here)
X: no.of carbon atoms
Y: no. of double bonds
Z: no. of carbon atoms from methyl end (OPPOSITE OF THE COOH END) to the carbon at double bond closest to methyl end
101
Fatty acid delta naming?
X: Y ^Z (^ to represent delta symbol here)
X: no. of carbon atoms
Y: no. of double bonds
Z: location of the double bond (from the COOH end)
102
How to determine length of fatty acid: (short, medium, long, very long)?
short: 2-4 carbons
medium: 6-12 carbons
long: 14-20 carbons
Very long: >22 carbons
103
What are micelles vs what are chylomicrons
what are chylomicrons composed of
micelle: lipid droplets enclosed by bile salt IN INTESTINAL LUMEN
chylomicrons: lipid carrying PROTEIN VESICLES IN BLOOD/LYMPH
chylomicrons made up of TAG, cholesterol, phospholipids, apolipoproteins
104
How do hormones (hint: 3 of them) aid fat digestion
Cholecystokinin: activates bile salts and pancreatic enzymes
Secretin: activates bicarbonate release to neutralize acidic bolus + provide optimum enzyme pH
105
Steps in fat digestion, absorption and transportation? Also include how micelles/chylomicrons contribute to the absorption and transportation process
1) Start with hydrolysis (alkaline hydrolysis) by pancreatic lipases in small intestine lumen
TAG > 2-monoacylglycerol + 2 fatty acids
2) THEN:
🡺Micelle formation for free fatty acids
🡺Absorption into enterocytes and micelle is broken
3a) For SHORT-MEDIUM chain free fatty acids:
Go into capillaries DIRECTLY but BOUND TO ALBUMIN
3b) For LONG/VERY LONG chain free fatty acids:
Recombine to form TAG
THEN FORM CHYLOMICRONS, transported into lymph
THEN chylomicrons join blood at left subclavian vein
106
Where are lipids stored in body?
Mostly in adipose tissue under skin (brown adipose and white adipose)
Minor storage in muscles and liver
107
How are fats stored in adipose tissue?
Glucose converted to G3P in adipose tissues (glucose enters by GLUT 4 channels)
In adipocytes: Glucose > DHAP > G3P
Chylomicrons in blood broken by lipoprotein lipase on fat cells,
triglycerides broken down to:
free fatty acids (enters adipocytes)
glycerol (goes to liver)
FFA > Fatty acid coA in liver > combined with G3P from glucose > Triglyceride in adipose tissue
108
How are lipids used as fuel molecules when required?
1st step: lipolysis
Hormone sensitive lipase stimulated by glucagon, breaks down TG into glycerol and 3 fatty acid
Glycerol and 3 FA carried to liver; 3 FA carried by albumin
Glycerol used for gluconeogenesis
3 FA used for fatty acid beta-oxidation, broken down to acetyl coA for Krebs cycle
109
How do lipids release energy during PROLONGED fasting? (process of formation, uptake of ketone bodies)
Lipolysis processes > beta-oxidation of fatty acids to acetyl coA
acetyl coA NOT fed into Krebs cycle during prolonged fasting - make ketone bodies in liver
liver DOES NOT have enzymes to break down ketone bodies for energy (eg thiophorase) - so ketone bodies transported out to blood
Ketone bodies taken up by extrahepatic tissues (eg muscles) and broken down to release energy
110
The process of de novo fatty acid synthesis?
Glucose uptake by liver > Krebs cycle > becomes citrate > acetyl coA > MALONYL coA
then malonyl coA enters fatty acid synthase complex (with use of NADPH)
then forms palmitate then fatty acyl coA
then fatty acyl coA combines with G3P (also from the glucose taken by liver glucose > DHAP > G3P, a portion of it does not enter Krebs cycle) to form triglycerides
TG exported out of liver by VLDL proteins (very low density lipoproteins with apolipoprotein 100) to blood
111
MCAT physiological cause? Medium chain fatty acyl coA dehydrogenase deficiency
symptoms?
Body does not have enough of Medium chain fatty acyl coA dehydrogenase
so cannot beta-oxidize fatty acids and break them down to acetyl coA for Krebs cycle
112
Symptoms and mechanism of Alcohol induced acute pancreatitis?
Alcohol damages pancreas
pancreatic a-amylase released into blood (amylase is a biomarker for the disease)
lack of enzyme because of pancreatic damage affects gut digestion of fatty acids
symptoms: Steatorrhea (fat rich stools)
113
The types of enzymes used in protein digestion in stomach and small intestine, where they are produced, how they are activated (if any) and their function?
Pepsin: breakdown of proteins to peptides in stomach, activated from pepsinogen to acids
Enteropeptidases: produced by enterocytes of small intestine, activates endopeptidases by protein cleavage
Exopeptidases: released by pancreas, breaks down longer peptide chains to smaller peptide chains in small intestine
includes: trypsin, chymotrypsin, elastase, carboxypeptidase A and B
activated by enteropeptidase proteolytic cleavage or by insulin from inactive forms (ZYMOGENS): trypsinogen, chymotrypsinogem, proelastase, procarboxypeptidase A and B
trypsin activated by enterokinase (a specific enteropeptidase)
Exopeptidases: produced in small intestine, cleaves terminal peptide chain to release 1 amino acid per time
di/tripeptidase: produced in enterocytes, breaks down dipeptides, tripeptides to amino acids
114
What process does amino acid absorption from lumen to enterocyte use?
how are amino acids absorbed into blood from enterocytes
Secondary active transport - Na+/K+ ATPase pump pumps out 3 Na+ out of enterocyte lumen for facilitated diffusion of amino acids and Na+ down concentration gradient by cotransporter protein
Amino acids diffuse into blood by facilitated transporter
115
What 2 systems help in protein degradation?
1) Ubiquitin-protease system, 2) lysozyme
116
How do the Ubiquitin-protease system and lysozyme system work? Explain briefly
Ubiquitin-protease system:
Target protein to be degraded covalently linked with ubiquitin using ATP
Ubiquitin-laced protein interacts with 26S proteosome, protein degraded to amino acids using ATP, back to amino acid pool for new protein synthesis
Ubiquitin released by deubiquitylating enzymes from ubiquitin-packed protein and recycled
Lysozyme:
Unwanted cellular proteins surrounded by membranes of lysozome and enters lysosomes by endocytosis
lysozyme (cathepsin) cleaves proteins into amino acids to be released back to amino acid pool
117
Transamination meaning?
Amino group of 1 amino acid transferred to 1 alpha-keto acid to make a new amino acid and a new alpha-keto acid
118
define deamination
Amino group of an amino acid is removed
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Processes of the Glucose Pyruvate Alanine cycle (Cahill cycle)
Its function?
During starvation:
glycolysis: glucose to pyruvate
Muscle proteins broken down to glutamate
Transamination in muscles: glutamate to alpha-ketoglutarate, pyruvate to alanine (by alanine aminotransferase)
Alanine transported by blood to liver
Transamination in liver: alanine to pyruvate, alpha-ketoglutarate to glutamate
ammonium ion from glutamate to urea cycle, excreted as urea in urine
pyruvate becomes glucose by gluconeogenesis
glucose transported back by blood to muscles for releasing energy and glycolysis (glucose to pyruvate) so 1 cycle
Function: AMINO ACID METABOLISM when amino acids in muscles need to be broken down for energy
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Fates of amino acid carbons and nitrogen (and for excess amino acids)
Transamination produces alpha-keto acids
carbon skeleton of excess amino acids converted to glucose or triglyceride
amino group of excess amino acids: transported by blood, goes into urea cycle and excreted as urea
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Processes of the urea cycle:
The amino group is transported as ammonium ion and ammonia in blood, for the liver to metabolise
*
Ammonium ion and amino group from aspartate combine to form urea
*
Urea is excreted via kidney
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WHY do you need oxygen (link to ATP production)
Oxygen: final electron acceptor at the electron transport chain
No oxygen to accept electrons then electron transport chain becomes blocked, protons cannot diffuse down ATP synthase pump
ATP CANNOT BE PRODUCED
CELLS CANNOT FUNCTION
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What is ATP composed of
Adenosine + ribose sugar + 3 phosphate groups
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Besides ATP what other molecule can also act as energy currency
Guanosine triphosphate (GTP)
125
Krebs cycle processes?
after acetyl coA to citrate:
citrate > isocitrate > alpha ketoglutarate > succinyl coA > succinate > fumarate > malate > oxaloacetate > citrate (loop)
enzymes used:
citrate > isocitrate: aconitase
isocitrate > alpha-ketoglutarate: isocitrate dehydrogenase
alpha ketoglutarate > succinyl coA: alpha ketoglutarate dehydrogenase
succinyl coA > succinate: succinate thiokinase
succinate > fumarate: succinate dehydrogenase
fumarate > malate: fumarase
malate > oxaloacetate: malate dehydrogenase
oxaloacetate > citrate: citrate synthase
NADH production: I AM producing NADH (at isocitrate, alpha ketoglutarate, malate)
FADH2: fumarate (during PRODUCTION of fumarate)
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What 2 parts does oxidative phosphorylation form
what complexes do the 2 parts have respectively
Electron transport chain, chemiosmosis
ETC: complex 1-4, coenzyme Q, cytochrome C
chemiosmosis: ATP synthetase
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The in-depth process of ETC?
NADH passes electrons to complex 1 to form NAD+
FADH2 passes electrons to complex 2 to form FAD
electrons in complex 1,2: passed on to coenzyme Q
electrons pass through: complex 3 > cytochrome c > complex 4
complexes serve as proton pumps: pump protons from matrix to mitochondrial intermembrane space (FORM PROTON GRADIENT)
complex 9 gives electrons to O2: produce water
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Process of chemiosmosis?
ATP synthase phosphorylates ADP to ATP using energy from proton movement
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ATP yield of 1 glucose molecule?
30-32 ATP yield
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The inhibitors to TCA cycle? If any, what are the clinical implications?
Rotenone, barbiturates: inhibit complex 1 (FADH2 can still donate electrons at complex 2)
Antimycin: inhibit complex 3 (electrons cannot be transferred beyond complex 3)
Cyanide, CO: Inhibit complex 4 (essentially the ETC is entirely blocked at the terminal), ATP cannot be produced > DEATH
oligomycins: inhibit ATP synthase proton channel (proton accumulation in intermembrane space)
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Clinical implications of uncoupling proteins when they malfunction OR when medications mimic their effects?
Uncoupling proteins: cause protons to leak into mitochondrial matrix WITHOUT generating energy as ATP
Energy released as heat
Aspirin and salicylates NSAIDs uncouple oxidative phosphorylation → cause fever in overdose
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Based on citric acid cycle, outline briefly production of carbohydrates, lipids, amino acids, nucleotides and porphyrins
Carbs: made from oxaloacetate (oxaloacetate to PEP then glucose)
lipids: made from citrate
amino acids: made from oxaloacetate, alpha-ketoglutarate
nucleotides, porphyrins: made from oxaloacetate, alpha-ketoglutarate, succinyl coA
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If all these intermediates in TCA cycle are siphoned out and depleted, what happens
TCA cycle becomes slower, reaction may stop halfway
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HOW do we prevent intermediates in TCA cycle from depletion
Anaplerotic reactions - 3 of them
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Which 3 anaplerotic reactions are there AND their locations
Pyruvate + HCO3- + ATP (reversible reaction, pyruvate carboxylase used) > oxaloacetate + ADP + Pi (liver, kidneys)
Phosphoenolpyruvate + CO2 + GDP (reversible reaction, PEP carboxykinase used) > oxaloacetate + GTP (heart, skeletal muscles)
Pyruvate + HCO3- + NAD(P)H (reversible, malic enzyme) > malate, NAD(P)+ (no specific tissue)
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Insulin function:
Promote storage of fuels:
1) glucose to glycogen in liver and muscle cells
2) converting glucose to triglycerides in liver, storage in adipose
3) amino acid uptake by muscle cells and protein synthesis
Promotes usage of glucose as fuel by facilitating its transport to muscle and fat cells
*
Inhibits fuel mobilization from stores like glycogen, triacylglycerols, and proteins
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Functions of Glucagon:
Counter-regulatory hormone to insulin
Maintains fuel availability when there is no dietary glucose:
*
Stimulates the release of glucose from liver glycogen
*
Stimulates the gluconeogenesis from lactate, glycerol, and amino acids
*
Mobilizes fatty acids from adipose triacylglycerol to provide an alternative source of energy
*
Glucagon has NO effect on skeletal muscle metabolism
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How does insulin stimulate glucose absorption in muscle/fat cells
Insulin stimulates GLUT 4 on cell surfaces to take up oxygen
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State the mechanism name by which blood glucose level is controlled
negative feedback of hormones
140
The 3 causes of diabetes?
Type 1 (immune cause)
Type 2 (insulin resistance due to fats)
Gestational diabetes
141
Define the following terms:
FGT, OGTT, Random Plasma Glucose Test
FGT (fasting glucose test): tests blood glucose level of a person who has not eaten in the last 8 hours
OGTT (Oral glucose tolerance test): tests blood glucose level after fasting and 1 and 2 hours after a person has drunk a glucose-containing beverage (1.75g/kg body weight)
Random plasma glucose test: measures blood glucose level WITHOUT regard to when the person last ate
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Why does OGTT require a morning start
Glucose tolerance has diurnal pattern - SIGNIFICANT decrease in the afternoon
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Requirements for OGTT test? (In terms of: diet, medication, sickness, alcohol, physical activity, fasting)
diet: > or equal to 150g of carbs per day preceding OGTT (inadequate food invalidates test results)
medication: withhold nonessential drugs 3 days before test (insulin secretion inhibited by salicylates, diuretics, anticonvulsants, oral contraceptives cause insulin resistance)
alcohol: NO INTAKE for 3 days before test
sickness: fever can cause diabetic-like response in OGTT
physical activity: normal physical activity before test (bed rest may impair glucose tolerance)
Fasting: patient must fast 8 hours before test
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Principle of glucose concentration detection in OGTT?
Glucose + H2O + O2 > gluconic acid + H2o2
H2o2 > H2O + 1/2 O2 (by peroxidase)
O2 oxidizes chromogen so chromogen (o-dianisidine) turns brown
concentration of brown oxidized chromogen found using spectrophotometer > obtain glucose conc.
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Which 2 types of fatty tissue in body and their morphology, functions and locations?
White adipose: 1 central lipid droplet, nucleus squeezed to side, for fuel storage (found under skin etc)
Brown adipose: several small lipid droplets, many mitochondria, found in kidneys and spine of newborns to keep them warm
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Energy sources for muscle contraction? AND the reactions involved in muscle contraction? (IF NO TIME JUST CHECK THE NPT PPT)
During light activities or rest: fatty acids, ketone bodies, blood glucose
Vigorous exercise (Bursts of heavy activities): muscle glycogen
The reaction for light activities/rest: fatty acids/ketone bodies/glucose + ADP + Pi > CO2 + ATP
Bursts of heavy activity: glycogen + ADP + Pi > lactate + ATP AND Phosphocreatine + ADP + Pi > creatine + ATP
muscle contraction leads to: ATP > ADP + Pi
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What is the function of creatine
maintain a continuous energy supply to your muscles during intense lifting or exercise
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Fuels for the brain? Their reactions? (IF NO TIME JUST CHECK THE NPT PPT)
Normally: glucose
starvation: ketone bodies
Reaction: glucose/ketone bodies + ADP + Pi > CO2 + ATP
Electrogenic transport by Na+/K+ ATPase: ATP > ADP + Pi
149
O2 debt effects?
rapid breathing after vigorous exercise to keep up with ATP synthesis
150
Effects of prolonged fasting?
1) muscles used as fuel
2) Fatty acid beta oxidation
3) Acetyl coA accumulation > ketone body formation
4) ketone bodies are acidic > ketone bodies in blood make blood acidic (ketoacidosis)
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Diabetic ketoacidosis causes and consequences?
EXTREME diabetes
normal glucose homeostasis is disrupted
abnormal fatty acid beta-oxidation starts, acetyl coA accumulates, large amounts of ketone bodies in blood produced as fuel
excessive ketone bodies in blood makes blood excessively acidic - fatal
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2 types of diabetes mellitus and their causes and development?
Type 1 DM:
Insufficient production of insulin as autoimmune system destroys beta cells
develops in early life (so aka juvenile diabetes/ insulin-dependent diabetes)
Type 2 DM:
Caused by insulin resistance, cells do not respond properly to insulin
Develops in late adulthood
associated with obesity
153
symptoms of diabetes?
Excessive urination and thirst - because of hyperglycemia
Acetone breath: ketone bodies broken down to acetone
Weight loss: lipid stores used as energy
Ketoacidosis
154
Processes of the Cori cycle? Purpose of Cori cycle?
Skeletal muscle use glycogen as emergency energy source
lactate produced and transported to liver by blood
lactate converted back to glucose by liver
glucose released back to blood for glycogen store in muscles
Purpose: to dissipate the lactate produced during anaerobic respiration
