Citric Acid Cycle/TCA cycle

Question 1

What kind of process do cells need to generate ATP?

Answer 1

a process that generates electricity in the mitochondria

Question 2

How do we create electricity?

Answer 2

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

Question 3

what is the final electron acceptor in ETC?

Answer 3

Oxygen!

Question 4

electron donor molecules (2)

Answer 4

NADH

FADH2

Question 5

how do we produce NADH and FADH2?

Answer 5

dehydrogenase enzymes!

in the citric acid cycle (Krebs cycle)

Question 6

CAC overview

Answer 6

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

Question 7

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

Answer 7

increase in glucagon, epinephrine, and cortisol

fatty acids are source of acetyl-coa

Question 8

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

Answer 8

increase in insulin

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

Question 9

in the liver (source of acetyl-coa?)

Answer 9

alcohol!

Question 10

external sources of acetyl-coA?

Answer 10

proteins

Question 11

CAC starting with glucose

Answer 11

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

Question 12

what inhibits isocitrate dehydrogenase

Answer 12

high ATP and high NADH inhibit isocitrate dehydrogenase

Question 13

what stimulates isocitrate dehydrogenase

Answer 13

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

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

Question 14

rate-limiting step of CAC

Answer 14

isocitrate dehydrogenase step!

Question 15

what does alpha-ketoglutarate dehydrogenase require to function?

Answer 15

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)

Question 16

what can disrupt CAC?

Answer 16

vitamin deficiency

Question 17

what else is succinate dehydrogenase a part of?

Answer 17

the ETC

it is complex II!

Question 18

what do we do with oxaloacetate product?

Answer 18

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

Question 19

control of CAC

Answer 19

speeds up when there is need for energy

slows down when there is a lot of energy

Question 20

do hormones control CAC?

Answer 20

NO!

Question 21

how does fatty acid synthesis fit into this?

Answer 21

Fatty acid oxidation produces acetyl-CoA which can enter CAC

Question 22

pyruvate dehydrogenase complex

Answer 22

combines pyruvate with CoASH

1 CO2 released, 1 NADH produced

Question 23

PDC enzymes and co-enzymes

Answer 23

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

Question 24

TPP

Answer 24

decarboxylation of alpha-keto acids

Question 25

NAD+

Answer 25

hyrdride transfer rxns

Question 26

FAD+

Answer 26

flavin coenzymes exist in 3 redox states

Question 27

coenzyme A

Answer 27

has reactive sulfhydryl group that carries acyl groups | very favorable

Question 28

lipoic acid

Answer 28

couples acyl-group transfer with electron transfer

Question 29

PDC is a...

Answer 29

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

Question 30

regulation of PDC

Answer 30

product inhibition or covalent modification

Question 31

regulation of PDC by product inhibition

Answer 31

high acetyl-CoA or NADH allosterically inhibit PDC

Question 32

regulation of PDC by covalent modification

Answer 32

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)

Question 33

citrate synthase regulation

Answer 33

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

Question 34

fluoroacetate

Answer 34

converted to fluorocitrate (potent inhibitor of aconitase) | blocks TCA cycle

Question 35

succinate dehydrogenase...why is it unique?

Answer 35

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

Question 36

malate dehydrogenase rxn energy

Answer 36

very unfavorable | it occurs because citrate synthase rxn is very favorable

Question 37

ATP from 1 glucose

Answer 37

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

Question 38

succinyl-CoA

Answer 38

feedback inhibitor of CAC

Question 39

enzymes of TCA associate as...

Answer 39

a metabolon channels substrates enables higher metabolic flux

Question 40

is CAC catabolic or anabolic?

Answer 40

catabolic bc endpoint is oxidative degradation of fuel | BUT, intermediates of CAC can be removed for biosynthetic processes (this makes it amphibolic - BOTH!)

Question 41

cataplerotic reactions

Answer 41

reactions that use CAC intermediates

Question 42

anaplerotic

Answer 42

reactions that replenish CAC intermediates

Question 43

glyoxosomes

Answer 43

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