Citric Acid Cycle

Question 1

oxidative decarboxylation

Answer 1

Irreversible oxidation process
pyruvate–>acetyl CoA
Carboxyl group removed (Co2)
PDH complex mechanism

Question 2

PDH complex

Answer 2

Irreversible oxidative decarboxylation
pyruvate–>acetyl CoA + CO2
5 cofactors: CoA-SH, NAD+, TPP, lipoate, FAD
3 enzymes

Question 3

NADH

Answer 3

Produced in PDH complex
Gives up hydride ion (H-) that carries 2 electrons to oxygen
Transfer of electrons ultimately generates 2.5 molecules of ATP per pair of electrons

Question 4

Four vitamins necessary in PDH complex

Answer 4

Thiamine/Vitamin B1 (TPP)
Riboflavin/Vitamin B2 (FAD)
Niacin/Vitamin B3 (NAD)
Pantothenate/Vitamin B5 (CoA)

Question 5

Coenzyme A

Answer 5

Cofactor in PDH complex
Acyl carrier
Reactive thiol (SH) critical to acyl carrier role
Derived from pantothenic acid

Question 6

Thiol of CoA purpose/mechanism

Answer 6

Necessary for acyl carrier role in CoA
Highly reactive
Covalently links to acyl groups
Forms thioesters

Question 7

Thiamine pyrophosphate (TPP)

Answer 7

Vitamin B1
Cleaves bonds adjacent to carbonyl group
Cofactor in pyruvate decarboxylase 
"Electron sink"
Binds tightly to E1 in PDH
First essential cofactor in PDH

Question 8

Lipoate

Answer 8

Cofactor in PDH complex
Amide linked to Lys of E2
Two thiol groups that can undergo reversible oxidation to a disulfide bond
Can be both electron (hydrogen) carrier and acyl carrier

Question 9

E1

Answer 9

Pyruvate dehydrogenase
Cofactor is TPP
Release Co2
Decarboxylates pyruvate
Transfers two electrons and acetyl group from TPP to lipoyllsyl group of E2

Question 10

E2

Answer 10

Dihydrolipoyl transacetylase

Question 11

E3

Answer 11

Dihydrolipoyl dehydrogenase

Question 12

Step 1

Answer 12

TPP attaches to pyruvate and removes carbonyl group (release of CO2)
Pyruvate is now aldehyde
Slowest step (rate limiting)

Question 13

Step 2

Answer 13

Transfer of two electrons and acetyl group from TPP to oxidized form of lipoyllsyl group of E2

Question 14

Step 3

Answer 14

Acetyl moiety (once pyruvate) transferred to -SH of lipoyl group
Then transferred to CoA to form acetyl CoA

Question 15

Step 4

Answer 15

Electron transfer of 2 hydrogen atoms from -SH groups of E2 to FAD of E3
Regeneration of disulfide (oxidized) form of lipoate

Question 16

Step 5

Answer 16

Reduced FADH2 of E3 transfers hydride ion to NAD+, forming NADH

Question 17

Substrate channeling

Answer 17

PDH complex
Intermediates never leave complex
Prevents theft of activated acetyl group by other enzymes

Question 18

Thiamine deficiency

Answer 18

Cannot oxidize pyruvate normally

Affect brain, which obtains energy from aerobic oxidation of glucose

Question 19

PDH activators

Answer 19

AMP, PDH phosphatase, NAD+, CoA

Question 20

PDH inhibitors

Answer 20

Acetyl CoA
NADH
PDH kinase
ATP