Citric Acid Cycle/TCA cycle Flashcards

1
Q

What kind of process do cells need to generate ATP?

A

a process that generates electricity in the mitochondria

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2
Q

How do we create electricity?

A

electron-rich molecules must transfer electrons to chain of complexes (electron transport chain)

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3
Q

what is the final electron acceptor in ETC?

A

Oxygen!

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4
Q

electron donor molecules (2)

A

NADH

FADH2

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5
Q

how do we produce NADH and FADH2?

A

dehydrogenase enzymes!

in the citric acid cycle (Krebs cycle)

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6
Q

CAC overview

A

8 rxns
acetyl-coa –> CO2
oxidation of pyruvate to CO2

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7
Q

starving state (what is our source of acetyl-coa and what are hormone levels like)

A

increase in glucagon, epinephrine, and cortisol

fatty acids are source of acetyl-coa

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8
Q

fed state (what is our source of acetyl-coa and what are hormone levels like)

A

increase in insulin

have plenty of acetyl-coa from breaking down glucose (mainly), fructose, and galactose

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9
Q

in the liver (source of acetyl-coa?)

A

alcohol!

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10
Q

external sources of acetyl-coA?

A

proteins

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11
Q

CAC starting with glucose

A

1) glycolysis converts 1 glucose to 2 pyruvate
2) 2 pyruvate enter mitochondria
3) pyruvate dehydrogenase makes acetyl-CoA, CO2, and NADH (from NAD+)

*this links glycolysis and CAC

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12
Q

what inhibits isocitrate dehydrogenase

A

high ATP and high NADH inhibit isocitrate dehydrogenase

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13
Q

what stimulates isocitrate dehydrogenase

A

high ADP stimulates isocitrate dehydrogenase because it tells the cell more energy is needed

high Ca2+ levels (calcium rises during work, work requires energy)

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14
Q

rate-limiting step of CAC

A

isocitrate dehydrogenase step!

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15
Q

what does alpha-ketoglutarate dehydrogenase require to function?

A
5 cofactors
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1. Thiamine (vitamin B1)
2. Lipoic acid
3. Coenzyme A (vitamin B5/pantothenate)
4. FAD+ (vitamin B2/riboflavin)
5. NAD+ (vitamin B3/niacin)
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16
Q

what can disrupt CAC?

A

vitamin deficiency

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17
Q

what else is succinate dehydrogenase a part of?

A

the ETC

it is complex II!

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18
Q

what do we do with oxaloacetate product?

A

oxaloacetate can join a new acetyl-CoA and start new cycle

19
Q

control of CAC

A

speeds up when there is need for energy

slows down when there is a lot of energy

20
Q

do hormones control CAC?

A

NO!

21
Q

how does fatty acid synthesis fit into this?

A

Fatty acid oxidation produces acetyl-CoA which can enter CAC

22
Q

pyruvate dehydrogenase complex

A

combines pyruvate with CoASH

1 CO2 released, 1 NADH produced

23
Q

PDC enzymes and co-enzymes

A
pyruvate dehydrogenase (TPP)
dihydrolipoyl transacetylase (lipoic acid and coenzyme A)
dihydrolipoyl dehydrogenase (NAD and FAD)
24
Q

TPP

A

decarboxylation of alpha-keto acids

25
Q

NAD+

A

hyrdride transfer rxns

26
Q

FAD+

A

flavin coenzymes exist in 3 redox states

27
Q

coenzyme A

A

has reactive sulfhydryl group that carries acyl groups

very favorable

28
Q

lipoic acid

A

couples acyl-group transfer with electron transfer

29
Q

PDC is a…

A

multi-enzyme complex
they are catalytically efficient
series of rxns occurs more rapidly

30
Q

regulation of PDC

A

product inhibition or covalent modification

31
Q

regulation of PDC by product inhibition

A

high acetyl-CoA or NADH allosterically inhibit PDC

32
Q

regulation of PDC by covalent modification

A

pyruvate dehydrogenase kinase is part of mammalian PDC

pyruvate dehydrogenase kinase is activated by NADH and acetyl-CoA (leads to phosphorylation and inactivation of E1)

33
Q

citrate synthase regulation

A

oxaloacetate binds, induces conformational change and facilitates binding of acetyl-CoA
NADH and succinyl-CoA allosterically inhibit citrate synthase

34
Q

fluoroacetate

A

converted to fluorocitrate (potent inhibitor of aconitase)

blocks TCA cycle

35
Q

succinate dehydrogenase…why is it unique?

A

it’s the only membrane-bound enzyme in the CAC

FAD is covalently bound to it and electrons stored in FADH2 are sent directly to ETC

36
Q

malate dehydrogenase rxn energy

A

very unfavorable

it occurs because citrate synthase rxn is very favorable

37
Q

ATP from 1 glucose

A

38 ATP
glycolysis: 2ATP + 2NADH (2 ATP + 6 ATP = 8 ATP)
PDC: 1 NADH per pyruvate (3 ATP x 2 = 6 ATP)
TCA: 3 NADH + FADH2 + GTP per acetyl-CoA (9+2+1)x2 = 24

38
Q

succinyl-CoA

A

feedback inhibitor of CAC

39
Q

enzymes of TCA associate as…

A

a metabolon
channels substrates
enables higher metabolic flux

40
Q

is CAC catabolic or anabolic?

A

catabolic bc endpoint is oxidative degradation of fuel

BUT, intermediates of CAC can be removed for biosynthetic processes (this makes it amphibolic - BOTH!)

41
Q

cataplerotic reactions

A

reactions that use CAC intermediates

42
Q

anaplerotic

A

reactions that replenish CAC intermediates

43
Q

glyoxosomes

A

plants use glyoxylate cycle to synthesize sugars from acetyl-CoA and to make oxaloacetate (they also use TCA cycle)