Citric acid cycle

Question 1

Step one enzyme

Answer 1

-citrate synthase

Question 2

Step one info

Answer 2

-citrate formed from Acetyl CoA and oxaloacetate
-Free energy of Acetyl CoA’s thioester drives the first metabolically irreversible reaction of TCA cycle
-Only TCA cycle reaction that forms a C-C double bond

Question 3

Step 2 enzyme

Answer 3

Aconitase

Question 4

Step 2 info

Answer 4

-Removes H2O from citrate to form C=C bond of cis-aconitate
-Re addition of H2O to form 2R,3S-Isocitrate which contains a secondary alcohol that can be biologically oxidized

Question 5

Step 3 enzyme

Answer 5

Isocitrate dehydrogenase

Question 6

Step 3 info

Answer 6

-Irreversible
-Alpha keto group formed by the removal of 2 H+ from secondary alcohol group
-Enzyme-bound oxalosuccinate intermediate

Question 7

Step 4 enzyme

Answer 7

Alpha-Ketoglutarate dehydrogenase

Question 8

Step 4 info

Answer 8

-oxidative decarboxylation of alpha-ketoglutarate reaction is similar to PDH
-irreversible
-produces succinyl CoA

Question 9

Succinyl CoA is a…

Answer 9

high energy thioester

Question 10

Step 5 enzyme

Answer 10

Succinyl-CoA synthetase

Question 11

Step 5 info

Answer 11

-Succinyl CoA reacts with free phosphate to form succinyl-phosphate and CoA
-Phosphoryl group transferred to His residue in the enzyme
-Phosphoryl group transferred to GDP forming GTP via substrate level phosphorylation

Question 12

Step 6 enzyme

Answer 12

Succinate dehydrogenase complex

Question 13

Step 6 info

Answer 13

-FAD-dependent dehydrogenase
-Produces fumarate via removal of 2 Hs to form a trans double bond

Question 14

Step 7 enzyme

Answer 14

Fumarase

Question 15

Step 7 info

Answer 15

addition of water to trans C=C bond forms L-malate

Question 16

Step 8 enzyme

Answer 16

Malate dehydrogenase

Question 17

Step 8 info

Answer 17

-uses 2 NAD+ to oxidize secondary alcohol of malate to a ketone group
-produces NADH and oxaloacetate

Question 18

Energy is conserved in these reduced coenzymes

Answer 18

3 NADH, 1 GTP, 1 FADH2

Question 19

_____ complex is a major regulatory point

Answer 19

PDH

Question 20

How is pyruvate dehydrogenase a regulatory point in TCA cycle?

Answer 20

• product inhibition by NADH and Acetyl CoA
  -Covalent modification- phosphorylation of E1

Question 21

Rate controlling steps

Answer 21

• pyruvate dehydrogenase
  -citrate synthase
  -Isocitrate dehydrogenase
  -alpha-ketoglutarate dehydrogenase complex

Question 22

Allosteric inhibitors of TCA cycle enzymes

Answer 22

• NADH and ATP

Question 23

Activators of TCA cycle enzymes

Answer 23

-ADP and Ca2+

Question 24

Step 1 PDH complex

Answer 24

E1 catalyzed by PDH
TPP decarboxylates pyruvate and forms hydroxyethyl TPP

Question 25

Step 2 PDH complex

Answer 25

Catalyzed by E1 using E2 as a substrate
Uses lipoamide cofactor as an oxidizing agent to convert HETPP to acetyl-dihydrolipoamide

Question 26

Step 2 PDH complex enzyme

Answer 26

Dihydrolipoyl transacetylase

Question 27

Step 3 PDH complex

Answer 27

E2 transfers acetyl group from dihydrolipoamide to HS-CoA

Question 28

Step 3 PDH complex enzyme

Answer 28

dihydrolipoyl dehydrogenase
coenzyme a is the third cofactor and second substrate

Question 29

Step 4 PDH complex

Answer 29

disulfide group of E3 oxidized the reduced lipoamide of E2
disulfide group serves an oxidant to convert dihydrolipoamide back to lipoamide

Question 30

Step 5 PDH complex

Answer 30

-FAD group of E3 oxidizes reduced dithiols of E2 forming FADH2
-FAD cofactor
-E3-FAD is reduced to E3-FADH that passes electrons to NAD+ to form NADH