Citric Acid Cycle Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

Citric Acid Cycle

A
  • Cyclic pathway in aerobic eukaryotic cells
  • Located in the mitochondrial matrix
  • Central role: links other biochemical pathways to the mitochondrial electron transport system (ETS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Amphibolic pathway

A
  • has catabolic functions (break down of metabolites to generate ATP, NADH and FADH2)
  • and anabolic functions (supplies precursors for other pathways)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Other complex roles of CAC

A
  • macrophages and dendritic cells respond to proinflammatory stimuli they undergo metabolic shifts, which include a ‘rewiring’ of the citric acid cycle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Inside the mitochondrion

A
  • Outer membrane (permeable to many metabolites)
  • Intermembrane space
  • Inner membrane (impermeable to many metabolites) – with numerous folds (cristae)
  • Matrix (inner compartment)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Citric Acid Cycle and Electron Transport System

A
  • Acetyl-CoA from other pathways enters the first reaction of the CAC: From (PDH) reaction, Fatty Acid beta-oxidation, Amino Acids reactions
  • NADH and FADH2 from the CAC and from other pathways transfer electrons to complexes in the ETS and “fuel” ATP synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Strategy to citric acid cycle

A
  • 2 carbon atoms enter the cycle as the acetyl group of acetyl-CoA
  • transferred to a 4C organic acid, oxaloacetate to yield a 6C tricarboxylic acid, citric acid (citrate ion in solution)
  • citrate enters a series of reactions during which two carbons are released as CO2
  • then remaining four carbons are regenerated as oxaloacetate through 4 reactions, for another run of the cycle
  • overall, irreversible pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Enzymes involved in citric acid cycle

A
  • citrate synthase
  • aconitase
  • isocitrate dehydrogenase
  • a-ketoglutarate dehydrogenase complex
  • succinyl CoA synthase
  • succinyl dehydrogenase
  • fumarase
  • malate dehydrogenase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

1st reaction of CAC

A
  • citrate synthase catalyses condensation of oxaloacetate and acetyl CoA
  • forms citrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

2nd reaction of CAC

A
  • aconitase catalyses isomerisation of citrate to isocitrate
  • citrate is dehydrated to form intermediate cis-aconitate
  • then rehydrated to form isocitrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

3rd reaction of CAC

A
  • isocitrate oxidised and decarboxylated to a-ketoglutarate

- catalysed by isocitrate dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

4th reaction of CAC

A
  • a-ketoglutarate undergoes oxidative decarboxylation to form succinyl-CoA
  • catalysed by a-ketoglutarate dehydrogenase complex
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

5th reaction of CAC

A
  • succinyl CoA hydrolysed to form high energy phosphate (i.e GTP)
  • catalysed by succinyl CoA synthase
  • intermediate formation of succinyl phosphate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

GTP

A
  • May be used to form ATP in a reaction catalysed by nucleoside diphosphokinase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

6th reaction of CAC

A
  • oxidation of succinate to fumarate

- catalysed by succinate dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

7th reaction of CAC

A
  • addition of water to fumarate to form malate

- catalysed by fumarase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

8th reaction of CAC

A
  • oxidation of malate to regenerate oxaloacetate

- catalysed by malate dehydrogenase

17
Q

Irreversible reactions in CAC

A
  • low product and slow reverse reaction

- drive cycle in forward direction

18
Q

Reversible reactions in CAC

A
  • favour production of malate and citrate which exit cycle and allow citrate to act as inhibitor
19
Q

CAC as a source of biosynthetic precursors

A
  • citrate: fatty acids, sterols
  • a-ketoglutarate: glutamate, other amino acids, purines
  • succinyl CoA: porphyrins, heme, chlorophyll
  • oxaloacetate: aspartate, phosphoenol-pyruvate, glucose
  • aspartate: other amino acids, purines, pyrimidines
20
Q

Anaplerotic reactions

A
  • replenishing pathways/reactions

- removal of intermediates from the pathway implies the need to replenish

21
Q

Fluoroacetate as a CAC inhibitor

A
  • isolated from plants
  • ‘suicide’ substrate as parent compound is non-toxic, but metabolism produces toxic product
  • binds to aconitase where fluorine binds to iron ion in active site, causing inhibition and death
22
Q

Malonate as a CAC inhibitor

A
  • 3 carbon homologue of succinate
  • similar in structure to succinate, allows it to bind to succinate dehydrogenase
  • competitive inhibitor
  • causes block - succinate, citrate and a-ketoglutarate build up
23
Q

Reduced cofactors generated in CAC

A
  • NADH

- FADH2

24
Q

Two phases in CAC

A
  • intro and oxidation if 2 carbons to carbon dioxide

- regeneration of oxaloacetate

25
Q

Redox coenzymes

A
  • 3 dehydrogenation reactions used NAD+ as redox coenzyme
  • step 6 uses FAD as redox coenzyme
  • FAD is more powerful oxidant than NAD+ and bound covalently to enzyme complex
26
Q

Overall equation for CAC

A
  • acetyl CoA + 2H2O + 3NAD+ + FAD + GDP + Pi —> 2CO2 + FADH2 + CoA-SH + GTP
  • then GTP + ADP —> ATP + GDP
27
Q

ATP yield - cell respiration

A
  • most of ATP generated through oxidative phosphorylation
  • NADH and FADH2 electrons will be transferred toward molecular O2
  • coenzymes will be oxidised again
  • proton gradient generated across inner mitochondrial membrane
  • ATP synthesis will take place through chemiosmotic coupling