tca cycle

Question 1

what is the purpose of the TCA cycle?

Answer 1

1. generate energy (GTP, NADH, FADH2)
2. provide intermediates for biosynthesis
3. provide feedback regulator (citrate) to other pathways

Question 2

what is the overall equation of the TCA cycle?

Answer 2

acetyl CoA + 3NAD+ + FAD + GDP + Pi→ CoA + 3NADH + FADH2 + GTP+ 2CO2

Question 3

where does the TCA cycle take place?

Answer 3

mitochondria:
- succinate dehydrogenase on inner membrane
- rest of enzymes in matrix

pyruvate moves into mitochondria fr cytosol as it converts to acetyl-CoA

Question 4

what is the rate limiting enzyme of TCA cycle?

Answer 4

isocitrate dehydrogenase

Question 5

which steps produce NADH? (3)

Answer 5

1. isocitrate→ a-KG
2. a-KG→ succinyl CoA
3. Malate→ oxaloacetate

“dehydrogenase”→ produces NADH/FADH2

Question 6

which step produce FADH2? (1)

Answer 6

succinate→ fumarate

Fumarate→ produces FADH2

Question 7

what stimulates/inhibits the TCA cycle?

Answer 7

stimulates: ADP (ie insufficient ATP, needs NADH & FADH2)

inhibits: ATP, NADH, FADH2 (dont need make more)

Question 8

how is pyruvate converted to acetyl CoA?

Answer 8

pyruvate dehydrogenase complex

Question 9

what substances are required for pyruvate dehydrogenase complex? (3)

Answer 9

made of 3 distinct enzymes (E1, 2, 3)
coenzymes:
1. thiamine pyrophosphate (fr vit B1)
2. lipoate, coenzyme A
3. FAD, NAD+

Question 10

how is PDH regulated? (2 pathways)

Answer 10

1. allosteric regulation (directly upregulates/inactivates PDH itself)
2. phosphorylation of PDH (activate/inactivate kinase and phosphatase that phosphorylates/dephosphrylates PDH, inactivating/activating it)

Question 11

how is PDH regulated during high energy need?(3)

Answer 11

1. increased NAD+ and CoASH→ increase PDH activity
2. increased Ca2+→ activate phosphatase to dephosphorylate/ activate PDH→ activates it
3. ADP/pyruvate inhibit kinase to activate PDH

Question 12

how is PDH regulated during low energy need?

Answer 12

1. increased NADH→ inhibit PDH complex
2. high NADH/acetyl CoA→ activate kinase to phosphorylate/inactivate PDH complex

Question 13

what diseases affect PDH? (3)

Answer 13

1. PDH deficiency
2. arsenic/mercury poisoning
3. thiamine/B1 deficiency

Question 14

what is the pathophysiology of pyruvate dehydrogenase deficiency? (2)

Answer 14

1. accumulation of pyruvate→ converted to lactate→ lactate acidosis
2. depletion of ATP→ neurological dysfunction/organ failure

Question 15

what is the pathophysiology of arsenic/mercury poisoning?

Answer 15

inhibits lipoic acid required for PDH/aKG DH→ decreased ATP production→ neurological dysfunction/organ failure

Question 16

what is thiamine/B1 used for in TCA cycle?

Answer 16

required for PDH and a-KG DH function

Question 17

what is the pathophysiology of thiamine deficiency?

Answer 17

decreased ATP production→ affects high O2 requiring organs→ beriberi

Question 18

how does high energy need affect TCA cycle regulation? (3)

Answer 18

e.g. exercise
increase ADP, increase Ca2+, decrease NADH→ activate:
1. isocitrate DH
2. aKG DH
3. malate DH

Question 19

how does low energy need affect TCA cycle regulation? (4)

Answer 19

e.g. resting
decrease ADP/increase ATP, increase NADH→ inhbits
1. isocitrate DH
2. aKG DH
3. malate DH
4. citrate synthase!!

Question 20

how does TCA cycle get replenished?

Answer 20

via OXALOACETATE!! (acetyl coa insufficient)
by pyruvate carboxylase + biotin (pyruvate→ oxaloacetate)

Question 21

which organ contains a high concentration of pyruvate carboxylase?

Answer 21

liver!
TCA intermediates are rapidly depleted by gluconeogenesis (to generate glucose while fasting) → need regenerate oxaloacetate

Question 22

what is the pathophysiology of TCA enzyme deficiency?

Answer 22

lack of TCA enzymes→ TCA cycle disrupted→ acetyl CoA not processed→ backward accumulation→ accumulate pyruvate & lactic acid→ lactic acidosis, neurological dysfunction