WEEK 2: Citric acid cycle

Question 1

what cells does the CAC take place in?

Answer 1

eukaryotic cells

Question 2

where in the cells does the CAC take place?

Answer 2

mitochondrial matrix

Question 3

what is the central role of the CAC?

Answer 3

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

Question 4

why is the CAC an amphibolic pathway?

Answer 4

has both catabolic functions and anabolic functions

Question 5

what catabolic functions does the CAC have?

Answer 5

break down of metabolites to generate ATP, NADH and FADH2

Question 6

what anabolic functions does the CAC have?

Answer 6

supplies precursors for other pathways

Question 7

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

Answer 7

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

​

Question 8

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

Answer 8

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

Question 9

what is coenzyme A?

Answer 9

an acyl carrier

Question 10

how is coenzyme A an acyl carrier?

Answer 10

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

Question 11

what occurs in the 1st reaction of the CAC?

Answer 11

oxaloacetate condenses with acetyl CoA to form citrate

Question 12

what enzyme catalyses reaction 1?

Answer 12

citrate synthase

Question 13

what occurs in the 2nd reaction of the CAC?

Answer 13

2a and 2b. Citrate is isomerized to isocitrate

Question 14

what is the intermediate compound of the second reaction?

Answer 14

cis-aconitate

Question 15

what enzyme catalyses reaction 2?

Answer 15

aconitase

Question 16

what occurs in the 3rd reaction of the CAC?

Answer 16

Isocitrate is oxidised and decarboxylated to alpha-ketoglutarate

Question 17

what enzyme catalyses reaction 3?

Answer 17

isocitrate dehydrogenase

Question 18

what is the intermediate compound of the third reaction?

Answer 18

oxalosuccinate

Question 19

what enzyme catalyses reaction 4?

Answer 19

alpha-ketoglutarate dehydrogenase complex

Question 20

what occurs in the 4th reaction of the CAC?

Answer 20

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

Question 21

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​

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

Answer 21

1.

Question 22

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

2. Photophosphorylation​
3. Cyclic phosphorylation​
4. Substrate-level phosphorylation​

Answer 22

4.

Question 23

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​

2. NADH and FADH2​
3. NAD+ and FAD​
4. ATP

Answer 23

2.

Question 24

what is citrate?

Answer 24

a tricarboxylic acid

Question 25

what occurs in the 5th reaction of the CAC?

Answer 25

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

Question 26

what enzyme catalyses reaction 5?

Answer 26

succinyl CoA synthetase with an intermediate formation of succinyl phosphate

Question 27

how can GTP form ATP?

Answer 27

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

Question 28

what occurs in the 6th step of the CAC?

Answer 28

Oxidation of succinate to fumarate

Question 29

what enzyme catalyses the 6th step?

Answer 29

succinate dehydrogenase

Question 30

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

Answer 30

FAD. FADH2

Question 31

what occurs in the 7th step?

Answer 31

addition of water to fumarate to form malate

Question 32

what enzyme catalyses step 7?

Answer 32

fumarase

Question 33

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

Answer 33

a water molecule is added

Question 34

what occurs in step 8 of the CAC?

Answer 34

oxidation of malate to regenerate oxaloacetate

Question 35

what enzyme catalyses step 8?

Answer 35

malate dehydrogenase

Question 36

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

Answer 36

228kcal/mol

Question 37

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

Answer 37

207kcal/mol

Question 38

what is the % of energy conservation of CAC

Answer 38

90 conservation

Question 39

what is the energy change for the TCA cycle

Answer 39

~ -13kcal/mol = energy lost as heat

Question 40

what best describes the purpose of the CAC?

Answer 40

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

Question 41

make fc of cac as a source of biosynthetic precursors

Question 42

what are anaplerotic reactions?

Answer 42

replenishing pathways/reactions

Question 43

cac inhibitors

Question 44

how many reactions are dehydrogenation reactions?

Answer 44

4 out of 8

Question 45

what reduced cofactors could be produced from a dehydrogenation reaction?

Answer 45

NADH or FADH2

Question 46

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

Answer 46

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

Question 47

what are the 2 phases of CAC?

Answer 47

introduction and oxidation of two carbons to carbon dioxide​ regeneration of oxaloacetate

Question 48

overall eq for CAC:

Answer 48

Overall equation (x2 for 1 glucose)​ Acetyl-CoA+ 2H2O + 3NAD+ + FAD + GDP + Pi ->​ -> 2CO2 + 3NADH + FADH2 + CoA-SH + GTP

Question 49

how is most the ATP produced here?

Answer 49

oxidative phosphorylation

Question 50

what is NAD+? What does it receive?

Answer 50

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

Question 51

what is FAD? What does it receive?

Answer 51

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

Question 52

what is the reduced form of NAD+?

Answer 52

NADH + H+

Question 53

what is the reduced form of FAD?

Answer 53

FADH2

Question 54

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

Answer 54

2.5 moles ATP

Question 55

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

Answer 55

1.5 moles ATP

Question 56

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

Answer 56

10 ATP 3 NADH --> 3 x 2.5 = 7.5ATP​ 1 FADH2 --> 1 x 1.5 = 1.5ATP​ 1 GTP --> = 1ATP​ ----------------------------​ Total =10 ATP

Question 57

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

Answer 57

substrate-level phosphorylation

Question 58

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

Answer 58

NADH and FADH2

Question 59

why is the CAC regulated?

Answer 59

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

Question 60

how is the rate of the CAC regulated?

Answer 60

to correspond to the rate of the ETS

Question 61

how is the rate of the ETS regulated?

Answer 61

by the ATP/ADP ratio and rate of ATP usage

Question 62

which points are the main control points of the pathway?

Answer 62

production of citrate all other 3 reactions that produce NADH

Question 63

what inhibits citrate synthase?

Answer 63

citrate

Question 64

what inhibits isocitrate dehydrogenase?

Answer 64

NADH

Question 65

what activates isocitrate dehydrogenase?

Answer 65

high concs of ADP

Question 66

what activates alpha-ketoglutarate dehydrogenase?

Answer 66

Ca2+

Question 67

what inhibits alpha-ketoglutarate dehydrogenase?

Answer 67

NADH

Question 68

what inhibits malate dehydrogenase?

Answer 68

NADH (inhibits all dehydrogenases)

Question 69

why is calcium an an activator important for muscle cells?

Answer 69

- 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

Question 70

HOW is citrate synthase inhibited?

Answer 70

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

Question 71

HOW does NADH inhibit malate dehydrogenase?

Answer 71

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

Question 72

how is O2 linked to CAC?

Answer 72

- 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

Question 73

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

Answer 73

due to reoxidation of NADH from glycolysis

Question 74

what is the purpose of anaplerotic reactions?

Answer 74

to replenish the CAC intermediates

Question 75

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

Answer 75

they get fully oxidised and released as CO2