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Biochem Block 2 > Pyruvate Dehyrdrogenase Complex > Flashcards

Pyruvate Dehyrdrogenase Complex Flashcards

1
Q

What are the 5 coenzymes for pyruvate dehydrogenase complex needs for its complete catalytic activity?

A
  • Thiamine pyrophosphate (TPP)
  • Lipoate (lipoic acids)
  • NAD+ (niacin derivative)
  • FAD (riboflavin derivative
  • Reduced coenzyme A (CoASH) (pantothenic acid derivative)
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2
Q

What does pyruvate decarboxylase (E1) require?

A

TPP

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3
Q

What does dihydrolipolytransacetylase (E2) require?

A

lipoic acid and CoA (pantothenic acid)

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4
Q

What does dihydrolipoyl deydrogenase (E3) require?

A

NAD+ (niacin) and FAD (riboflavin)

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5
Q

When is PDC active?

A

in the dephosphorylated state by PDC phosphatase

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6
Q

When is PDC inactive?

A

PDC kinase, which phosphorylates it

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7
Q

What is PDC kinsae inhibited by?

A

ADP and pyruvate

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8
Q

What does arsenite inhibit?

A

all the enzymes requiring lipoic acid as a coenzyme, including E2 of the a-ketoglutarate dehydrogenase complex

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9
Q

What does arsenite do?

A

it forms a stable complex with thiol groups of lipoic acid, making it unavailable, which leads to inefficient conversion of pyruvate to acetyl coA, so pyruvate and consequently lactic acid accumulate

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10
Q
  • X-linked dominant
  • congenital lactic acidosis
  • neurodegernation, muscle spasticity, early death
A

Pyruvate dehydrogenase (PDH E1) deficiency

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11
Q

why is there brain degeneration in yruvate dehydrogenase (PDH E1) deficiency?

A

The brain is sensitive to acidosis due to increased conversion of pyruvate to lactate.

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12
Q

What occurs in Leigh Syndrome/subacute necrotizing encephalomyelopathy?

A
  • defects in mitochondrial ATP production due to mutations in the PDH complex
  • brain is unable to produce sufficient ATP since PDH complex is inactive, so thiamine or niacin deficiencies cause serious CNS problems
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13
Q

What are some vitamins that the TCA Cycle require to function?

A

niacin (NAD+), riboflavin (FAD and FMn), pantothenic acid (coenzyme A), thaimine, Mg2+, Ca2+, Fe2+, and phosphate)

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14
Q

What is the rate limiting enzyme for TCA cycle?

A

isocitrate dehydrogenase

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15
Q

increased levels of what activate the TCA cycle?

A

ADP

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16
Q

increased levels of what inhibits the TCA cycle?

A

NADH

17
Q

What can citrate be removed from the TCA cycle for?

A

Fatty Acid Synthesis

18
Q

What can alpha-ketoglutarate be removed from the TCA cycle for?

A

Amico Acid synthesis/neurotransmitter

19
Q

What can Succinyl CoA be removed from the TCA cycle for?

A

heme synthesis

20
Q

What can Malate be removed from the TCA cycle for?

A

gluconeogenesis

21
Q

What can Oxaloacetate be removed from the TCA cycle for?

A

Amino Acid Synthesis

22
Q

What is one of the major anapleurotic enzymes in the cell?

A

Pyruvate carboxylase

23
Q

Pyruvate carboxylase is found in what tissues?

A

liver, brain, adipocytes, fibroblasts

24
Q

Pathways that replenish the intermediates of the TCA cycle are reffered to as what

A

Anapleurotic - “filling up”

25
Q

What enzyme converts Acetyl CoA to Citrate?

A

Citrate synthase

26
Q

What enzyme converts Citrate to Isocitrate?

A

Aconitase

27
Q

What enzyme converts Isocitrate to a-Ketoglutarate?

A

Isocitrate dehydrogenase

28
Q

What enzyme converts a-Ketoglutarate to Succinyl CoA?

A

a-Ketoglutarate dehydrogenase

29
Q

What enzyme converts Succinyl CoA to Succinate?

A

succinate thiokinase

30
Q

What enzyme converts Succinate to Fumarate?

A

Succinate dehydrogenase

31
Q

What enzyme converts Fumarate to Malate?

A

Fumarase

32
Q

What enzyme converts Malate to Oxaloacetate?

A

Malate dehydrogenase

33
Q

What is one of the major anapleurotic enzymes in the cell?

A

pyruvate carboxylase

34
Q

What are the steps of the TCA cycle?

A

Acetyl CoA -> Citrate ->Isocitrate -> Alpha-ketoglutarase ->Succinyl CoA -> Succinate -> Fumarate -> Malate -> Oxaloacetate

35
Q

The PDH complex converts what to what?

A

Pyruvate to Acetyl CoA

36
Q

Which subunit binds TPP and catalyzes the decarboxylation reaction?

A

E1

37
Q

Which subunit binds transacylase and is involved in the ox-red part of the reaction?

A

E2

38
Q

Which subunit reduces NAD+?

A

E3

39
Q

what does aresenite inhibit?

A

all the enzymes requiring lipoic acid as a coenzyme

Biochem Block 2 (12 decks)

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