TCA Cycle Flashcards

1
Q

The TCA cycle _____ two carbons of acetate from acetyl CoA and generates NADH and FAD2H. In anabolism, it generates key intermediates for _____, _____, and _____

A

Oxidizes
Gluconeogenesis
Fatty acid synthesis
Amino acid synthesis

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2
Q

The TCA cycle occurs in the ___ of the mitochondria. The outer membrane is permeable to most molecules. The inner membrane is very ____. This allows a proton concentration gradient to be established across the ____ ___ of the mitochondria

A

Matrix
Impermeable
Inner membrane

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3
Q

The matrix naturally has ___ proton concentration. The inter-membrane space has naturally ____ proton concentration

A

Low
High

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4
Q

The electron transport chain requires genes and proteins from both ____ and ____ DNA

A

Nucleus
Mitochondrial

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5
Q

Mitochondrial DNA is more similar to _____ DNA then nucleus DNA

A

Prokaryotic

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6
Q

Mitochondrial DNA is _____ because it is naked, and not bound to histones in a chromatin structure. It is exposed to hire concentrations of ____ ____ ____. The mitochondrial DNA polymerase has limited ability to repair DNA damage.

A

Hypermutatable

Reactive oxygen species

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7
Q

Mitochondrial DNA is dynamic. There are multiple ____ of the mitochondrial DNA to help push back from the hypermutability, especially in energetics cells like ___ cells

A

Copies
Muscle

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8
Q

Many symptoms of mitochondrial disease are ____ due to energy starvation during fetal development

A

Neurological

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9
Q

Glycolysis occurs in the ____. Pyruvate, dehydrogenase, and the TCA cycle occur in the _____.

A

Cytosol
Mitochondria

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10
Q

Pyruvate is transported to the mitochondria via the _____ ____ ____ which acts as a heterodimer of two subunits: ____ and ____
MPC is located on the ____ ____ of the mitochondria.

A

Mitochondrial pyruvate carrier (MPC)
MPC1 and MPC2
Inner membrane

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11
Q

Inherited mutations in the mitochondrial pyruvate carrier causes ____ _____

A

Lactic acidosis

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12
Q

____ ____ is the link between glycolysis and the TCA cycle. It has four subunits. E1 subunit is ____ ____, with a thiamine pyrophosphate. E2 is a _____ with Lipoate and CoA. E3 is a ____ with FAD and NAD+. Keto acid dehydrogenase and branch chain ketoacid dehydrogenase share a similar organization.

A

Pyruvate dehydrogenase
Pyruvate decarboxylase
Transacetylase
Dihydrolipoyl dehydrogenase

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13
Q

Pyruvate dehydrogenase is regulated by reversible _____. When activated the ___ ___ will proceed. When inhibited, pyruvate will be converted into ____.

A

Phosphorylation
TCA cycle
Lactate

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14
Q

Pyruvate dehydrogenase is regulated by phosphorylation and dephosphorylation of ____ residues in ____ alpha subunits

A

Serine
E1

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15
Q

Pyruvate is converted into ____ by pyruvate dehydrogenase which then bonds to coenzyme A, forming ____

A

Acetate
Acetyl CoA

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16
Q

All reactions of the TCA cycle take place in the ____ ____

A

Mitochondrial matrix

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17
Q

Overview of TCA cycle:

A
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18
Q

____ ____ is the key rate limiting enzyme in the TCA cycle

A

Isocitrate dehydrogenase

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19
Q

The reaction from acetyl-CoA to citrate is energy yielding however, the following reaction is not energetically favorable. This allows for ____ to build up and be used as an intermediate for other biosynthetic reactions. This is like wise for ____.

A

Citrate
Malate

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20
Q

First step:
The enzyme ____ ____ hydrolyzes, the Theoester bond of acetyl CoA to join acetate and oxaloacetate, forming ____. Citrate has three carboxylic acid groups, making it a tricarboxylic acid.

A

Citrate synthesis
Citrate

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21
Q

Second step:
The enzyme ____ catalyzes a two step isomerization to convert citrate to _____, which is a tricarboxylic acid

A

Aconitase
Isocitrate

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22
Q

Third step:
____ ____ catalyzes this oxidative decarboxylate, isocitrate is converted into ____. It uses NAD+ and creates____. IDH1 in the cytosol and IDH2 in the mitochondria catalyze the same reaction but use ____ instead

A

Isocitrate dehydrogenase (IDH3)
Alpha-ketoglutarate
NADH
NADP+

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23
Q

Isocitrate dehydrogenase removes an ____ group from 6 carbon Isocitrate forming the 5 carbon alphaketoglutarate. _____ is a byproduct

A

Carboxyl
CO2

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24
Q

Fourth step:
_______ _____ catalyzes the final oxidative decarboxylation, forming _______ from alpha ketoglutarate. ____ and ____ are byproducts

This product is then added to acetyl CoA similar to pyruvate dehydrogenase enzyme.

A

Alpha-ketoglutarate dehydrogenase
succinyl CoA
NADH
CO2

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25
Q

Alpha ketoglutarate dehydrogenase removes a carboxyl group from the ____ carbon alpha-ketoglutarate forming the ___ carbon succinyl CoA.

At this point ___ carbons have been released as carbon dioxide, but not the same carbons that entered as acetyl CoA

A

5
4
2

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26
Q

Review:
Look at cofactors

A
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27
Q

Fifth step:
_____ ____ cleaves the Theoester bond, linking succinate and CoA this is a strongly extra Gondek reaction and the enzyme uses the energy to catalyze substrate level phosphorylation of GDP to make GTP. The end product is ____.

A

Succinate thiokinase

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28
Q

Sixth step:
____ _____ oxidizes succinate to introduce a double carbon-carbon bond forming ____. FAD is reduced to ___. Succinate dehydrogenase is a component of the electron transport chain transferring electrons from FAD2H to _____.

A

Succinate dehydrogenase
Fumarate
FAD2H
Coenzyme Q

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29
Q

Seventh step:
_____ _____ it’s a proton and hydroxyl from water to fumarate double bond forming ____.

A

Fumarate hydratase
Malate

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30
Q

Eighth step:
____ ____ oxidizes malate’s hydroxyl to a keto group forming _____ and reducing NAD+ to NADH in the process

A

Malate dehydrogenase
Oxaloacetate

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31
Q

In the TCA cycle overall,
1 two carbon acetyl group and two waters become 2 carbon dioxides.
The net production goes on to make ___ ____

A

10 ATP

32
Q

In the liver, in the fasted and starved states, ____ is high because of fatty acid Beta-oxidation. This prevents acetyl CoA from oxidation in the ____ ___, and drives it towards ketone body synthesis

A

NADH
TCA cycle

33
Q

Isocitrate dehydrogenase is the rate limiting step of the TCA cycle, activity is regulated by the ratio of ____ to ____ in the mitochondria. ADP binding to one subunit changes the conformation of other subunits to alter their affinity for substrate.

A

ADP
ATP

34
Q

The presence of ADP results in more ___ ____ enzyme activity, up regulating the TCA cycle. ADP is an _____ ____

A

Isocitrate dehydrogenase
Allosteric activator

35
Q

_____ acts as an Allosteric activator of NAD+ dependent Isocitrate dehydrogenase (IDH3). This is a ____ ____ regulation

A

Citrate
Feedforward activation

36
Q

Which amino acids can be generated from the TCA cycle intermediates through transamination reactions?

A

Aspartate and glutamate, their side chains can be transaminated, transaminases use vitamin 6 as a cofactor

37
Q

____ reactions increase the capacity of the TCA cycle. Every time an intermediate leaves the cycle, the capacity decreases. ____ reactions help replenish the TCA cycle

A

Anaplerotic
Anaplerotic

38
Q

_____ participates in fatty acid synthesis when it leaves the TCA cycle
_____ participates in amino acid synthesis and is a Neuro transmitter
____ participate in heme synthesis
_____ participates in gluconeogenesis
_____ participates in amino acids synthesis

A

Citrate
Alpha-ketoglutarate
Succinyl-CoA
Malate
Oxaloacetate

39
Q

____ ____ is a Anaplerotic reaction that converts pyruvate to oxaloacetate which can then join acetyl CoA to form citrate

A

Pyruvate carboxylase

40
Q

______ ____ pathway in muscles is a type of Anaplerotic reaction. When muscle cells are working, they require a lot of ATP. ____ ____ converts a AMP to inosine monophosphate (IMP). This results in an increase in blood _____.

____ _____ takes a carbon from Aspartate to form fumarate, regenerating ____.

A

Myoadenylate deaminase
Myoadenylate deaminase
Ammonium
Adenylsuccinate
AMP

41
Q

______ ____ _____ is from inherited mutations in the gene coding the muscle specific AMPD1 isoform of AMP deaminase results in an inactive enzymes. This makes individuals ___ intolerant because the TCA Cycle can’t be replenished in response to work

A

Myoadenylate deaminase deficiency
Exercise

42
Q

TCA cycle intermedius influence _____ Gene expression through epigenetic regulation. _____ is the substrate for histone acetyl transferences. ____ and ____ block histone and cytosine demethylases

A

Nuclear
Acetyl CoA
Succinate
fumarate

43
Q

If there is a mutation in succinate dehydrogenase, there is a buildup of ____ which promotes the methylation of nuclear DNA leading to changes in transcriptional patterns, which can ultimately lead to ____

A

Succinate
Cancer

44
Q

____ ____ is a tumor suppressor.

A

Succinate dehydrogenase

45
Q

____ _____ _____ uses molecular oxygen to hydroxylate the methyl carbon from lysine. During this reaction, alpha-ketoglutarate is decarboxylated to ____. Therefore, An increase in succinate promotes the methylation of lysine rather than the demethylation

A

Jumanji domain demethylases (JHDM)
Succinate

46
Q

2-hydroxyglutarate is an ______, meaning it interferes with the function of alpha-ketoglutarate utilizing dioxygenase enzymes, sometimes leading to cancer

A

Oncometabolite

47
Q

Gain of function mutations in the ____ ____ causes the enzyme to run in reverse reducing alpha-ketoglutarate to 2-hydroxyglutarate

A

Isocitrate dehydrogenase

48
Q

2-hydroxyglutarate acts as a ____ ____ for me deoxygenated, as such as the Jumanji domain lysine demethylases, causing _____ within the cell

A

Competitive inhibitor
Hypermethylation

49
Q

Inhibition of ____ _____ and ____ ___ causes hypermethylation and changes the transcriptional program of the cell at specific genes that promote proliferation and inhibit differentiation and apoptosis. Leading to uncontrolled cell division and cancer

A

Lysine demethylases (KDMs)
Cytosine demethylases (TET2)

50
Q

______ of proline and lysine residues in _____ is also dependent on alpha-ketoglutarate dependent dioxygenases.

A

Hydroxylation
Collagen

51
Q

Alpha-ketoglutarate dependent dioxygenases regulate diverse processes with the cell. When mutations in ____ _____ occur, 2-hydroxylglutarate accumulates causing changes in gene expression and oxygen sensor which can contribute to cancer.

Increased ____ inhibits all of these reactions because it is the product of Isocitrate dehydrogenase

A

Isocitrate dehydrogenase
Succinate

52
Q

Succinate dehydrogenase acts as a tumor suppressor, it’s substrate, succinate, builds up and inhibits ______ ____ ____ such as HIF prolyl hydroxylase. This stabilizes HIF and promotes a pro survival metabolism

A

Alpha-ketoglutarate dependent dioxygenases

53
Q

____ ____ are also alpha-ketoglutarate dependent dioxygenases. In oxygen sensing, _____ is a substrate for prolyl hydroxylation, which signals its destruction in the presence of oxygen

A

Prolyl hydroxylases (PHDs)
Hypoxia inducible factor HIF

54
Q

Many ____ ____ inhibit alpha-ketoglutarate dependent dioxygenases. Mutations in the ___ ____ enzymes cause a build up of these oncometabolites and contribute to cancer

A

Tricarboxylic acids
TCA cycle

55
Q

Model of pyruvate dehydrogenase cofactors:

A
56
Q

Which of the substances below is used as a substrate by lysine methyltransferase enzymes?
Formate, formaldehyde, adenosylmethionine,

A

Adenosylmethionine

57
Q
A

NADH

58
Q
A

At low substrate concentration, the presence of ADP results in more enzyme activity

59
Q

ADP is an _____ ____ of Isocitrate dehydrogenase

A

Allosteric activator

60
Q

Citrate changes the ____ of Isocitrate dehydrogenase

A

Vmax

61
Q

Citrate is a ____ ____ of Isocitrate dehydrogenase. The Vmax increases when citrate is added

A

Allosteric activator

62
Q

Citrate acts as an activator of Isocitrate dehydrogenase, meaning it is a _____ activation

A

Feedforward

63
Q
A

Tumor suppressor

64
Q

Which oncometabolite below accumulates from a gain of function mutation?

A

2-hydroxyglutarate

65
Q

What type of enzymes are inhibited by the oncometabolite 2-hydroxyglutarate?

A

Dioxygenase

66
Q
A

Lysine methyltransferase

67
Q

The rate limiting step in the TCA cycle is activated by___

A

ADP

68
Q
A

Alpha-ketoglutarate and Succinate

69
Q
A

The mother carries the same mutation but at a lower frequency than the child

70
Q
A

Elevated glycolysis to compensate for decreased mitochondrial function

71
Q
A

There is no chance that you will pass this mutation to offspring, it is only maternally inherited

72
Q
A

Zero

73
Q
A

2.5 moles

74
Q
A

Succinate

75
Q
A

Succinate

76
Q
A

Dinitrophenol DNP

77
Q
A

Cytochrome C