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MSK Week 1 > TCA Cycle > Flashcards

TCA Cycle Flashcards

1
Q

What is so special about the TCA cycle?

A

Major energy producing pathway in the body

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2
Q

Where does the TCA cycle occur?

A

Mitochondria

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3
Q

In what form does food product reach the TCA cycle?

A

Acetyl CoA

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4
Q

What is the general idea of the CA cycle?

A

Take Acetyl CoA and oxidize it to make carbon dioxide and water in order to make energy.

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5
Q

Where are all of the enzymes we need for the TCA cycle?

A

All the enzymes of the TCA cycle are in the mitochondrial matrix except succinate dehydrogenase, which is in the inner mitochondrial matrix

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6
Q

Acetyl CoA and ozaloacetate condense to form what?

A

Citrate

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7
Q

What enzyme condenses acetyl-CoA and oxaloacetate to make citrate?

A

Citrate synthase

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8
Q

Citrate is isomerized to what?

A

Isocitrate

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9
Q

What enzyme turns citrate to isocitrate?

A

Aconitase

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10
Q

Isocitrate is oxidized to what?

A

Alpha ketoglutarate

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11
Q

What two step process is involved in turning isocitrate to alpha ketoglutarate?

A

Oxidation
Decarboxylation

(CO2 is produced and the electrons are passed to NAD+ to form NADH and H+)

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12
Q

What enzyme turns isocitrate to alpha ketoglutarate?

A

Isocitrate dehydrogenase

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13
Q

What activates isocitrate dehydrogenase? Inhibits it?

A

This key regulatory enzyme of the TCA cycle is allosterically activated by ADP and inhibited by NADH

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14
Q

What happens to alpha ketoglutarate once it is made?

A

converted to succinyl-CoA

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15
Q

Alpha ketoglutarate to Succinyl-CoA is an example of what kind of reaction?

A

oxidative decarboxylation reaction

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16
Q

What enzyme turns alpha-ketoglutarate to succinyl CoA?

A

α-ketoglutarate dehydrogenase

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17
Q

What cofactors are required for α-ketoglutarate dehydrogenase?

A

This enzyme requires five cofactors: thiamine pyrophosphate, lipoic acid, CoASH, FAD, and NAD+

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18
Q

What happens to succinyl CoA?

A

cleaved to succinate

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19
Q

How do we get energy from the succinyl CoA to succinate reaction?

A

Cleavage of the high-energy thioester bond of succinyl-CoA provides energy for the substrate-level phosphorylation of GDP to GTP

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20
Q

What enzyme cleaves succinyl CoA to succinate?

A

succinate thiokinase aka succinyl-CoA synthetase

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21
Q

What happens to succinate?

A

oxidized to fumarate

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22
Q

What electron carrier is involved at the step where sucinate becomes fumarate?

A

succinate transfers two hydrogens together with their electrons to FAD, which forms FADH2

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23
Q

What enzyme oxidizes succinate to fumarate?

A

succinate dehydrogenase

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24
Q

Where does the succinate to fumarate rxn occur?

A

Inner mitochondrial membrane

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25
Q

What happens to fumarate?

A

Converted to malate

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26
Q

What enzyme turns fumarate to malate?

A

Fumarase

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27
Q

How does fumarase turn fumarate to malate?

A

Adds water across the double bond

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28
Q

What happens to malate?

A

Oxidized to regenerate oxaloacetate

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29
Q

What oxidizes malate to oxaloacetate?

A

Malate dehydrogenase

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30
Q

What enzyme carrier is involved with the malate dehydrogenase rxn?

A

two hydrogens along with their electrons are passed to NAD+, producing NADH and H+

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31
Q

How much ATP per NADH?

A

2.5 ATP

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32
Q

How much ATP per FADH2

A

1.5

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33
Q

How much ATP per turn of the TCA cycle?

A

1 mole of acetyl CoA gives us 10 moles of ATP

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34
Q

What happens during fasting?

A

Intermediates of the TCA cycle are utilized in the fasting state in the liver for the production of glucose and in the fed state for the synthesis of fatty acids

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35
Q

What are anaplerotic reactions?

A

Anaplerotic reactions replenish intermediates of the TCA cycle as they are removed for the synthesis of glucose, fatty acids, amino acids, or other compounds

36
Q

One of the most important anaplerotic reactions?

A

Carboxylation of pyruvate to oxaloacetate

37
Q

What enzyme carboxylates pyruvate to oxaloacetate?

A

pyruvate carboxylase

38
Q

What cofactor does pyruvate carboxylase need?

A

Biotin

39
Q

What activates the enzyme pyruvate carboxylase besides its cofactor biotin?

A

Acetyl-CoA

40
Q

Where is pyruvate carboxylase found?

A

Liver
Brain
Adipose Tissue

41
Q

What reactions do amino acids do to produce TCA intermediates?

A

Anaplerotic reactions

42
Q

What amino acids form glutamate?

A

Glutamine, proline, arginine and histidine

43
Q

What amino acid forms aspartate?

A

Asparagine

44
Q

What becomes oxaloacetate?

A

Aspartate

45
Q

Name of the reaction type that turns aspartate to oxaloacetate

A

Transamination

46
Q

How is Succinyl CoA formed?

A

Propionyl-CoA gets converted to methylmalonyl-CoA and subsequently to Succinyl-CoA

47
Q

Formation of propionyl CoA

A

You need Valine, isoleucine, methionine and threonine

48
Q

What amino acids make fumarate?

A

Phenylalanine, tyrosine, and aspartate

49
Q

What pathway slows down the TCA cycle?

A

Gluconeogenesis, which uses intermediates of the TCAcycle

50
Q

What happens to the TCA cycle as glucose is synthesized?

A

malate or oxaloacetate is removed from the TCA cycle and replenished by anaplerotic reactions

51
Q

Pyruvate is formed by what compounds?

A

Lactate or alanine

52
Q

What product of the TCA cycle is important for fatty acid synthesis?

A

Citrate

53
Q

What catalyzes the anaplerotic reactions that replenish the TCA cycle intermediates?

A

Pyruvate Carboxylase

54
Q

How can we get amino acids from glucose via the oxaloacetate pathway?

A

Glucose is converted to pyruvate, which forms oxaloacetate, which by transamination forms aspartate and, subsequently, asparagine

55
Q

How can we get amino acids from glucose via the oxaloacetate and acetyl CoA pathway?

A

Glucose is converted to pyruvate, which forms both oxaloacetate and acetyl-CoA, which condense, forming citrate. Citrate forms isocitrate and then α-ketoglutarate, from which glutamate, glutamine, proline, and arginine are produced

56
Q

What accelerates the ETC?

A

When ADP levels are high relative to ATP the reactions of the electron transport chain are accelerated.

57
Q

What speeds up the TCA cycle?

A

NADH is rapidly oxidized by the ETC; consequently, the TCA cycle speeds up

58
Q

What slows down the ETC?

A

When the concentration of ATP is high the electron transport chain slows down

59
Q

What slows down the TCA cycle?

A

When the concentration of ATP is high the electron transport chain slows down, NADH builds up, and consequently the TCA cycle is inhibited

60
Q

How, specifically, does the TCA cycle slow down (this is very involved, but think about the process)

A

NADH allosterically inhibits isocitrate dehydrogenase. Isocitrate accumulates, and because the aconitase equilibrium favors citrate, the concentration of citrate rises. Citrate inhibits citrate synthase, the first enzyme of the cycle.

61
Q

What happens to oxaloacetate when NADH is high?

A

Oxaloacetate is converted to malate when NADH is high and, therefore, less substrate (OAA) is available for the citrate synthase reaction

62
Q

What reactions are NAD used in?

A

isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate dehydrogenase reactions

63
Q

What is niacin important for?

A

Niacin is used for the synthesis of the nicotinamide portion of NAD

64
Q

What is important for the production of FAD?

A

Riboflavin

65
Q

What is thiamine important for?

A

the synthesis of thiamine pyrophosphate

66
Q

Importance of Pantothenate?

A

synthesis of CoASH

67
Q

Effects of low Vitamin A

A

Night blindness and xerophthalmia

68
Q

Effects of low Vitamin D

A

Inadequate bone mineralization, rickets in children

69
Q

Effects of low Vitamin E

A

Reproductive failure, muscular dystrophy, neurologic abnormalities

70
Q

Effects of low Vitamin K

A

Defective blood coagulation

71
Q

Effects of low Vitamin C

A

Scurvy

72
Q

Effects of low thiamine?

A

Berriberi

73
Q

Effects of low riboflavin?

A

Oral-buccal cavity lesions

74
Q

Effects of low niacin?

A

Pellagra (diarrhea, dermatitis, dementia, death)

75
Q

Effects of low Vitamin B6

A

Convulsions, dermatitis, anemia

76
Q

Effects of low Folate

A

Megaloblastic Anemia

77
Q

Effects of low Vitamin B12?

A

Megaloblastic Anemia and neurological symptoms

78
Q

Effects of low biotin

A

Anorexia, nausea, vomitis, glossitis, alopecia

79
Q

Effects of low pantothenic acid

A

Listlessness, fatigue, burning feet syndrome

80
Q

How do Carbons from glucose enter the TCA cycle?

A

In order for carbons from glucose to enter the TCA cycle, glucose is first converted to pyruvate by glycolysis, then pyruvate forms acetyl-CoA

81
Q

How is acetyl CoA formed?

A

Pyruvate dehydrogenase catalyzes the oxidative decarboxylation of pyruvate, forming acetyl-CoA

82
Q

Where is pyruvate dehydrogenase?

A

Pyruvate dehydrogenase, a multienzyme complex located exclusively in the mitochondrial matrix

83
Q

What is similar between pyruvate dehydrogenase and alpha ketoglutarate?

A

They need the same 5 components

84
Q

What is different between pyruvate dehydrogenase and alpha ketoglutarate?

A

In contrast to α-ketoglutarate dehydrogenase, a pyruvate dehydrogenase exists in a phosphorylated (inactive) form and a dephosphorylated (active) form

85
Q

How is pyruvate decarboxylase deactivated?

A

CoASH and NAD+. Can also be inactivated by ADP

86
Q

What activates the pyruvate decarboxylase?

A

The products of the pyruvate dehydrogenase reactions, acetyl-CoA and NADH. It is activated specifically by a phosphatase

87
Q

How is pyruvate decarboxylase controlled, generally?

A

When the concentration of substrates is high, the dehydrogenase is active, and pyruvate is converted to acetyl-CoA. When the concentration of products is high, the dehydrogenase is relatively inactive

MSK Week 1 (14 decks)

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