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APO510 - MEDICAL BIOCHEMISTRY > WEEK 2: Citric acid cycle > Flashcards

WEEK 2: Citric acid cycle Flashcards

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USMLE® Step 1 flashcards
1
Q

what cells does the CAC take place in?

A

eukaryotic cells

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2
Q

where in the cells does the CAC take place?

A

mitochondrial matrix

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3
Q

what is the central role of the CAC?

A

links other biochemical pathways to the mitochondrial electron transport system (ETS)

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4
Q

why is the CAC an amphibolic pathway?

A

has both catabolic functions and anabolic functions

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5
Q

what catabolic functions does the CAC have?

A

break down of metabolites to generate ATP, NADH and FADH2

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6
Q

what anabolic functions does the CAC have?

A

supplies precursors for other pathways

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7
Q

how is the CAC ‘rewired’ in macrophages and dendritic cells when they respond to proinflammatory stimuli?

A
  • glycolysis increases​
  • oxidative phosphorylation decreases​
  • CAC intermediates accumulate and are diverted to support the immune cell function​

​

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8
Q

Acetyl-CoA is involved in the first reaction of the CAC. Where does the substrate come from?

A

From the Pyruvate Dehydrogenase (PDH) reaction​

From Fatty Acid beta-oxidation​

From Amino Acids reactions

From ketone bodies formed in the liver when insulin levels are low

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9
Q

what is coenzyme A?

A

an acyl carrier

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10
Q

how is coenzyme A an acyl carrier?

A

it has a thiol group as a reactive part of the molecule - this binds the acyl groups as thiol esters

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11
Q

what occurs in the 1st reaction of the CAC?

A

oxaloacetate condenses with acetyl CoA to form citrate

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12
Q

what enzyme catalyses reaction 1?

A

citrate synthase

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13
Q

what occurs in the 2nd reaction of the CAC?

A

2a and 2b. Citrate is isomerized to isocitrate

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14
Q

what is the intermediate compound of the second reaction?

A

cis-aconitate

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15
Q

what enzyme catalyses reaction 2?

A

aconitase

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16
Q

what occurs in the 3rd reaction of the CAC?

A

Isocitrate is oxidised and decarboxylated to alpha-ketoglutarate

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17
Q

what enzyme catalyses reaction 3?

A

isocitrate dehydrogenase

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18
Q

what is the intermediate compound of the third reaction?

A

oxalosuccinate

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19
Q

what enzyme catalyses reaction 4?

A

alpha-ketoglutarate dehydrogenase complex

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20
Q

what occurs in the 4th reaction of the CAC?

A

Succinyl-CoA is formed by the oxidative decarboxylation of alpha-ketoglutarate

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21
Q

Which of these represents the overall equation of the citric acid cycle in animal cells?
1. Acetyl-CoA+ 2H2O + 3NAD+ + FAD + GDP + Pi -> 2CO2 + 3NADH + FADH2 + CoA-SH + GTP​

  1. Acetyl-CoA -> 2CO2 + 3NADH + FADH2 + CoA-SH + GTP​
  2. Acetyl-CoA+ H2O + NAD+ + FAD + GDP + Pi -> CO2 + NADH + FADH2 + CoA-SH + GTP​
  3. Acetyl-CoA+ 2H2O + 3NAD+ + FAD + ADP + Pi -> 2CO2 + 3NADH + FADH2 + CoA-SH + ATP
A

1.

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22
Q

Which process generates ATP from ADP and inorganic phosphate (Pi) in glycolysis and the citric acid cycle (via GTP)?​
1. Oxidative phosphorylation​

  1. Photophosphorylation​
  2. Cyclic phosphorylation​
  3. Substrate-level phosphorylation​
A

4.

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23
Q

Which compounds have stored the majority of the chemical energy from glucose, by the end of glycolysis, pyruvate dehydrogenase reaction and the citric acid cycle?
1. ATP and CO2​

  1. NADH and FADH2​
  2. NAD+ and FAD​
  3. ATP
A

2.

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24
Q

what is citrate?

A

a tricarboxylic acid

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25
Q

what occurs in the 5th reaction of the CAC?

A

Generation of a high energy phosphate from the hydrolysis of succinyl CoA

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26
Q

what enzyme catalyses reaction 5?

A

succinyl CoA synthetase with an intermediate formation of succinyl phosphate

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27
Q

how can GTP form ATP?

A

GTP may be used to form ATP in a reaction catalysed by nucleoside diphosphokinase:
GTP + ADP  ATP + GDP

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28
Q

what occurs in the 6th step of the CAC?

A

Oxidation of succinate to fumarate

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29
Q

what enzyme catalyses the 6th step?

A

succinate dehydrogenase

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30
Q

what is the electron carrier in step 6? What is it’s reduced form?

A

FAD.
FADH2

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31
Q

what occurs in the 7th step?

A

addition of water to fumarate to form malate

32
Q

what enzyme catalyses step 7?

A

fumarase

33
Q

how does the double bond turn into a simple covalent bond from fumarate to malate in step 7?

A

a water molecule is added

34
Q

what occurs in step 8 of the CAC?

A

oxidation of malate to regenerate oxaloacetate

35
Q

what enzyme catalyses step 8?

A

malate dehydrogenase

36
Q

how much energy is available in one mole of acetyl-CoA?

A

228kcal/mol

37
Q

how much energy is contained in the products of CAC cycle?

A

207kcal/mol

38
Q

what is the % of energy conservation of CAC

A

90 conservation

39
Q

what is the energy change for the TCA cycle

A

~ -13kcal/mol = energy lost as heat

40
Q

what best describes the purpose of the CAC?

A

oxidises the C atoms from acetyl groups to CO2, stores some of the energy from acetyl groups into reduced electron carriers (v important) and produces some ATP

41
Q

make fc of cac as a source of biosynthetic precursors

A
42
Q

what are anaplerotic reactions?

A

replenishing pathways/reactions

43
Q

cac inhibitors

A
44
Q

how many reactions are dehydrogenation reactions?

A

4 out of 8

45
Q

what reduced cofactors could be produced from a dehydrogenation reaction?

A

NADH or FADH2

46
Q

how is the formation of ATP different in animal cells and plant cells in step 5?

A

animal cells produce GTP from the first reaction which then reacts with ADP to produce ATP.
Plant cells form ATP directly

47
Q

what are the 2 phases of CAC?

A

introduction and oxidation of two carbons to carbon dioxide​

regeneration of oxaloacetate

48
Q

overall eq for CAC:

A

Overall equation (x2 for 1 glucose)​

Acetyl-CoA+ 2H2O + 3NAD+ + FAD + GDP + Pi ->​

-> 2CO2 + 3NADH + FADH2 + CoA-SH + GTP

49
Q

how is most the ATP produced here?

A

oxidative phosphorylation

50
Q

what is NAD+? What does it receive?

A

co-enzyme of dehydrogenases. ELECTRON CARRIER involved in the oxidation of many metabolites.
Receives 2 electrons and 1 proton

51
Q

what is FAD? What does it receive?

A

Prosthetic group of flavoproteins. TRANSFERS electrons as hydrogen atoms.
Receives 2 electrons and 2 protons

52
Q

what is the reduced form of NAD+?

A

NADH + H+

53
Q

what is the reduced form of FAD?

A

FADH2

54
Q

the oxidation of one NADH in the elcetron chain produces how much ATP?

A

2.5 moles ATP

55
Q

the oxidation of one FADH2 in the elcetron chain produces how much ATP?

A

1.5 moles ATP

56
Q

what is the total yield of ATP from the oxidation of one acetyl CoA molecule?

A

10 ATP

3 NADH –> 3 x 2.5 = 7.5ATP​
1 FADH2 –> 1 x 1.5 = 1.5ATP​
1 GTP –> = 1ATP​

—————————-​

Total =10 ATP

57
Q

which process generates ATP from ADP in glycolysis and in the citric acid cycle?

A

substrate-level phosphorylation

58
Q

which compounds have stored the majority of the chemical energy from glucose by the end of glycolysis, pyruvate dehydrogenase and CAC?

A

NADH and FADH2

59
Q

why is the CAC regulated?

A

to maintain ATP homeostasis. This specific pathway makes the link between all catabolic pathways in the cell and ETS.

60
Q

how is the rate of the CAC regulated?

A

to correspond to the rate of the ETS

61
Q

how is the rate of the ETS regulated?

A

by the ATP/ADP ratio and rate of ATP usage

62
Q

which points are the main control points of the pathway?

A

production of citrate
all other 3 reactions that produce NADH

63
Q

what inhibits citrate synthase?

A

citrate

64
Q

what inhibits isocitrate dehydrogenase?

A

NADH

65
Q

what activates isocitrate dehydrogenase?

A

high concs of ADP

66
Q

what activates alpha-ketoglutarate dehydrogenase?

A

Ca2+

67
Q

what inhibits alpha-ketoglutarate dehydrogenase?

A

NADH

68
Q

what inhibits malate dehydrogenase?

A

NADH (inhibits all dehydrogenases)

69
Q

why is calcium an an activator important for muscle cells?

A
  • their function energy is required in the form of ATP.
  • Ca2+ increases the rate of the CAC, and the rate of production of reduced electron carriers
  • More reduced electron carriers provided for oxidative phosphorylation
  • coordinated with the activation of muscle contraction
70
Q

HOW is citrate synthase inhibited?

A

increased conc of citrate implies low oxaloacetate. Enzyme switched off - then acetyl-CoA is diverted to other pathways, eg for fatty acid synthesis

71
Q

HOW does NADH inhibit malate dehydrogenase?

A

the malate enzyme is influenced by NADH/NAD+ ratio.
- low levels of NADH switches enzyme on

72
Q

how is O2 linked to CAC?

A
  • O2 is needed to regenerate NAD+
  • lack of O2 leads to build up of NADH
  • increased lactate in the heart muscle - angina (the heart muscle does not normally work anaerobically
73
Q

why does the conc of lactate increase in muscle cells during hypoxia?

A

due to reoxidation of NADH from glycolysis

74
Q

what is the purpose of anaplerotic reactions?

A

to replenish the CAC intermediates

75
Q

what happens to the carbon atoms from sugars, fatty acids and amino acids during the process of cell respiration?

A

they get fully oxidised and released as CO2

APO510 - MEDICAL BIOCHEMISTRY (12 decks)

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