Pyruvate and TCA cycle Flashcards

1
Q

What are the 6 sources of pyruvate?

A

malate, lactate, alanine, glycolysis, serine, cysteine

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2
Q

What are the 4 fates of pyruvate?

A

Oxaloacetate, lactate, alanine, Acetyl CoA

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3
Q

What is the major fate of pyruvate?

A

Acetyl CoA

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4
Q

Why would pyruvate avoid going into Oxaloacetate?

A

Because it requires too much energy

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5
Q

If pyruvate can not convert into acetyl CoA, what would be the next best choice?

A

Lactate or alanine

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6
Q

What is the enzyme that converts Pyruvate to Acetyl CoA?

A

PDH complex

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7
Q

Name the co-factors of pyruvate

A

Tpp, NAD+, FAD, CoA-sh, Lipoic acid

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8
Q

Which cofactor is needed for PDH complex?

A

Lipoic acid

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9
Q

Tpp is vitamin __

A

B1

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10
Q

FAD is vitamin___ and also called ___.

A

B2 and riboflavin

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11
Q

CoA-sh is vitamin ___ and also known as ____

A

B5 and pantothenic acid

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12
Q

NAD is vitamin___ and also called ____

A

B3 and niacin

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13
Q

What is PDH complex inhibited by?

A

ATP and NADH

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14
Q

What is the PDH complex activated by?

A

AMP

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15
Q

What happens if TPP is deficient?

A

Will present with symptoms of PDH complex deficiency

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16
Q

Which 2 cycles does PDH complex link?

A

Glycolysis and TCA

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17
Q

In the presence of O2 which cycle does pyruvate go into?

A

TCA

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18
Q

In absence of O2 which cycle does pyruvate go into?

A

Lactate

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19
Q

How many ATP are produced from pyruvate converting to lactate?

A

2

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20
Q

Name the 3 catalytic enzymes of PDH complex

A

Pyruvate dehydrogenase/decarboxylase (E1)
Dihydrolipolyl transacetylase(E2)
Dihydrolipolyl dehydrogenase(E3)

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21
Q

Name the 2 regulatory enzymes of PDH complex

A

PDH kinase
PDH phosphatase

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22
Q

Is PDH complex active or inactive when phosphorylated?

A

Inactive

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23
Q

Is PDH complex active or inactive when dephosphorylated?

A

Active

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24
Q

What brings about dephosphorylation ?

A

Insulin

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25
Q

What does PDH kinase do to the complex?

A

Inactivate it

26
Q

What inhibits PDH kinase?

A

ADP and pyruvate

27
Q

What activates PDH kinase?

A

Acetyl CoA and NADH

28
Q

What does PDH phosphatase do to the complex?

A

Activate it

29
Q

What activates PDH phosphatase?

A

Calcium

30
Q

What causes acidosis?

A

Build up of lactic acid
-lactic acid lowers pH

31
Q

What happens if there’s an energy deficit of PDH deficiency?

A

-A deficiency in this enzymatic complex limits the production of Acetyl CoA and thus citrate
-Brain problems

32
Q

Which 2 substrates bind to form citrate in the TCA cycle?

A

Acetyl CoA and OAA

33
Q

Name the four enzymes that bring about production of NADH and FADH2

A

Malate, alpha-ketoglut, isocitrate, succinate dehydrogenase

34
Q

What is the rate limiting step of TCA cycle?

A

Isocitrate Dehydrogense

35
Q

Which step in the pathway requires the co-factors used in PDH complex?

A

Alpha-ketoglutarate dehydrogenase

36
Q

Name another complex where succinyl dehydrogenase is used?

A

ETC

37
Q

What inhibits and activates Isocitrate dehydrogenase?

A

Inhibitors: NADH and ATP
Activator: ADP

38
Q

What can be used to treat PDH deficiency?

A

-Cofactor supplementation with thiamine, carnitine, and lipoic acid is the standard of care.
- Ketogenic diets (with restricted carbohydrate intake) have been used to control lactic acidosis with minimal success.

39
Q

Which step in the TCA cycle uses GTP?

A

Succinyl CoA to Succinate

40
Q

What inhibits aconitase?

A

Flurocitrate

41
Q

How much ATP is produced when 4 dehydrogenases go to the ETC?

A

9

42
Q

How much ATP is produced from the GTP reaction?

A

1

43
Q

What inhibits citrate synthase?

A

Citrate

44
Q

What activates the dehydrogenases?

A

Calcium

45
Q

What inhibits α-ketoglutarate dehydrogenase?

A

succinyl CoA and NADH
Arsenate

46
Q

What inhibits Succinate dehydrogenase?

A

OAA

47
Q

Name the 3 enzymes that are inhibited by arsenite poisoning (requires lipoic acid)?

A

1) Pyruvate dehydrogenase complex,
2) Alpha keto glutarate dehydrogenase complex and
3) Alpha ketoacid dehydrogenase complex.

48
Q

How much ATP is produced overall for the TCA cycle?

A

20

49
Q

What are the sources of acetyl CoA?

A

Palmitate, Acetoacetate, Glucose, Pyruvate, Ethanol

50
Q

What’s the role of TCA cycle in gluconeogenesis?

A

TCA cycle intermediates beyond Alpha-ketoglutarate are potentially
glucogenic

51
Q

Which amino acids can form acetyl coa?

A

leucine, lsoleucine, and tyrosine

52
Q

Which amino acids can form fumurate?

A

phenylalanine and tyrosine

53
Q

Which amino acids can form acetoacetyl coa?

A

leucine, lysine, tryptophan, tyrosine

54
Q

Which amino acids can form pyruvate?

A

cysteine, glycine, alanine, hydrox-proline, serine, threonine

55
Q

Which amino acids can form succinyl coa?

A

Isoleucine, valine, methionine

56
Q

Which amino acids can form alpha-ketoglutarate?

A

Glutamate, proline, histamine, arginine

57
Q

Which amino acids can form OAA?

A

arginine and aspartate

58
Q

What’s the role of TCA cycle in fatty acid synthesis?

A

Acetyl CoA is the major substrate for long-chain fatty acid synthesis
Acetyl Co A can also be used for the synthesis of cholesterol, steroids etc.

59
Q

Describe the role of TCA cycle in purine and pyrimidine synthesis

A

1) Succinyl Co A is utilized for Heme synthesis as well as for utilization of ketone bodies.
2) Acetyl Co A is utilized for the synthesis of fatty acids, steroids, cholesterol, ketone bodies as well as Acetyl Choline
3) Glutamic acid is a precursor of GABA, an inhibitory neurotransmitter

60
Q

Why is the TCA cycle termed as amphibolic?

A

TCA cycle functions in both oxidative and synthetic processes, thus, it is
amphibolic

61
Q

What can cause thiamine deficiency?

A

Chronic alcoholism