Metabolism 3: CAC Flashcards

1
Q

Where is Acetyl CoA formed?

A

Mitochondria

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2
Q

What can Acetyl-CoA be used for?

A

ketone bodies, CAC, fatty acids, sterols

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3
Q

What can form Acetyl-CoA

A
Pyruvate (oxidaiton)
Fatty Acids (beta ox)
Amino acids (Deamination and oxidation)
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4
Q

What are the 3 places we get NADH in the TCA cycle?

A

Isocitrate ->a-ketoglutarate
a-ketoglutarate->succinyl-CoA
Malate -> Oxaloaceteate

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5
Q

Where do we get GTP formed in TCA cycle?

A

Succinyl CoA -> Succinate

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6
Q

Where do we get FADH2 formed in TCA cycle?

A

succinate -> fumarate

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7
Q

List the sequence of substances of hte TCA cycle starting from Pyruvate

A

pyruvate -> Acetyl CoA -> citrate -> isocitrate ->a-ketoglutarate -> succinyl CoA -> succinate -> fumarate -> malate -> oxaloacetate

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8
Q

Where does CAC take place?

A

Primarily in the mitochondria inner membrane and matrix where hte CAC enzymes are located

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9
Q

How do we go from a 6C compound to oxaloacetate, a 4C compound at the end of CAC

A

Lose 2 C in form of carbon dioxide via oxidation

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10
Q

What happens to the NADH generated?

A

Used within mitochondria in the ETC rxn to generate ATP, which is then exported out of the mitochondria as ADP is imported in

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11
Q

In total, what is generated in cycle of the CAC

A

3 NADH, 1 FADH2, 1 GTP, 2CO2

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12
Q

How many ATP/GTP is generated by 1 round of CAC

A

10 (9 ATP: 7.5 from 3 NADH, 1.5 from FADH2 and 1 GTP)

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13
Q

Where does the ATP come from?

A

Electron transfer from substrates to molecular Oxygen provides energy to create ATP as well as water

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14
Q

What are the course control regulations of the citric acid cycle?

A

Major mechanism for regulation; important for exercise, flight or fight response
levels of ADP(rate limiting):

NADH, FADH2,

Acetyl CoA: related to PDH and transport of fatty acids to mitochondria

Oxaloacetate: affected by pathways depleting CAC intermediates

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15
Q

What are the fine control regulators of the CAC?

A

Under baseline condition: no desperate need for energy
Allosteric regulation
Isocitrate dehydrogenase
a-ketoglutarate dehydrogenase

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16
Q

Does higher concentration of ATP, GTP, and NADH stimulate or inhibit CAC?

17
Q

Does higher concentration of ADP and calcium stimulate or inhibit CAC?

18
Q

What are the activators /inhibitors for isocitrate dehydrogenase

A

Fine control regulation
Activator: ADP
Inhibitors: ATP, NADH

19
Q

What are the activators/inhibitors for a-ketoglutarate dehydrogenase?

A

Fine control regulation
Activator: Calcium
Inhibitor: NADH, Succinyl CoA, ATP, GTP

20
Q

What happens wiht high cellular activity in course control

A

ATP decreases and ADP increases -> increases CAC activity

21
Q

What happens with low oxygen in course control

A

Increased NADH, FADH2 -> lack of NAD+ and FAD will decrease CAC

22
Q

What CAC intermediate contributes to fatty acid and sterol synthesis?

23
Q

What CAC intermediate contributes to amino acid synthesis?

A

a-ketoglutarate

Oxaloacetate

24
Q

What CAC intermediate contributes to gluconeogenesis?

25
What CAC intermediate contributes to heme synthesis?
Succinyl CoA
26
What can replenish a-ketoglutarate in the CAC
amino acid (glutamate)
27
What can replenish succinyl coA in the CAC
Valine and Isoleucine -> propioniyl CoA -> Succinyl CoA
28
What can replenish fumarate in the CAC
amino acids (aspartate, phenylalanine, tyrosine)
29
What can replenish oxaloacetate in the CAC
Aspartate
30
What can replenish pyruvate?
Amino acids
31
What casues PDH deficiency?
mutations in E1 alpha gene -> E1 becomes inactive | Inherited in X linked dominant (all others are autosomal recessive)
32
What is typically seen with PDH deficiency in children?
inc serum lactate, pyruvate, alanine chronic lactic acidosis cyst formation
33
How is PDH deficiency treated?
dietary supplementation with thiamine, carnitine, and lipoic acids
34
What causes fumarase deficiency?
Mutations in the fumarase gene and disrupts the conversion of fumarate to malate and thus the CAC
35
What are some sx seen with fumarase deficiency?
Severe Neurological Impairment: Encephalopathy, Dystonia Increased urinary excretion of fumarate, succinate, a-ketoglutarate, citrate
36
What are treatments for fumarase deficiency
no effective treatment currently
37
What can fluoroacetate (rat poison) do?
Directly inhibits aconitase which converts citrate to cis aconitate in the CAC before changing to isocitrate Inhibits the CAC