Lecture 27: Glucose Catabolism (Citric Acid Cycle)

Question 1

Citric Acid Cycle (CAC) Overview

What are other names for CAC?

Answer 1

Tricarboxylic Acid Cylce (TCA) or Krebs Cycle

Question 2

Citric Acid Cycle (CAC) Overview

How many units of CO2 are produced?

Answer 2

2

Question 3

Citric Acid Cycle (CAC) Overview

What product of pyruvate begins the CAC?

Answer 3

Acetyl CoA

Question 4

Citric Acid Cycle (CAC) Overview

What does Acetyl CoA react with to initiate the CAC?

Answer 4

oxaloacetate

start and finish of CAC

Question 5

Citric Acid Cycle (CAC) Overview

What is produced through the CAC?

Answer 5

1 GTP (energy equvilent to ATP)
3 NADH
1 FADH2

Question 6

Citric Acid Cycle (CAC) Overview

What is the general equation for the CAC?

Answer 6

Acetyl-CoA + 3 NAD + FAD + GDP + Pi + 2 H2O
–>
2 CO2 + 3 NADH + FADH2 + GTP + CoA + 3 H

Question 7

Citric Acid Cycle (CAC) Overview

Why is it called the Citric Acid cycle?

Answer 7

The first product, the 6-carbon unit, is citic acid

Question 8

Citric Acid Cycle (CAC) Overview

How much ATP can NADH and FADH2 produce through oxidative phosphorilation?

Answer 8

1 NADH = 2.5 ATP
1 FADH2 = 1.5 ATP

Question 9

CAC in Eukaryotes

Where does the CAC occur?

Answer 9

mitochondrial matrix
(vs in cytosol for bacteria)

Question 10

CAC in Eukaryotes

Where does oxidative phosphorylatoin occur?

Answer 10

mitrochondria innter membrane

Question 11

CAC in Eukaryotes

What are the intermediates from CAC used for?

Answer 11

biosynthesis of: AA, nucleotides, fatty acids, sterols, etc

Question 12

The Bridging Step: Oxidative Decarboxylation of Pyruvate

What enam catalyzed the transition from pyruvate to Acetyl CoA?

Answer 12

Pyruvate dehydrogenase

regulated by phosphorylation

Question 13

The Bridging Step: Oxidative Decarboxylation of Pyruvate

What are the 5 cofactors required for pyruvate dehdrogenase?

Answer 13

TPP, lipoic acid, and FAD (prosthetic groups)
NAD and CoA-SH (co-substrates)

Question 14

The Bridging Step: Oxidative Decarboxylation of Pyruvate

Q from Slides: The conversion of 1 mole of pyruvate to 3 mol of CO2 via pyruvate dehydrogenase and the CAC also yield ____ mol of NADH, ____ mol of FADH2, and ____ mol of ATP (GTP)?

Answer 14

4 mol NADH
1 mol FADH2
1 mol ATP (GTP)

Pyruvate to Acetyl CoA produce an extra NADH

Question 15

CAC

How many steps/enzymes are there for the CAC?

Answer 15

8

Question 16

CAC

Step 1:

Answer 16

C-C bond formation to make Citrate:
condensation between a 2-carbon units (oxaloacetate, OAA) and 4 carbon units (acetyl-CoA) to make 6 carbon units (Citric Acid)
catalyzed by citrate synthase

The first 2 CO2 produced originate from the OAA not acetyl-CoA

Question 17

CAC

Step 2:

Answer 17

Isomerization via dehydration/rehydration:
Aconitase isomerized citrate to isocitrate as isocitrate is easily oxidized. Converts the 3° alcohol to 2° alcohol (switches the OH group)
dehydrogenation first to cis-Aconitate then rehydration to form isocitrate

Question 18

CAC

Step 3:

Answer 18

Oxidative decarboxylations to give NADH:
Isocitrate dehydrogenase oxidiazed the isocitrate to oxalosuccinate (a-keto acid), which forms NADH. Oxalosuccinate is than decarboxylated to for a-ketoglutarate

Question 19

CAC

Step 4:

Answer 19

Oxidative decarboxylations to give NADH and CO2:
a-ketoglutarate dehydrogenase oxidatively decarboxylates a-ketoglutarate into succinyl-CoA
irreversible, regulated by product inhibition

final oxidative decarboxylation

Question 20

CAC

Step 5:

Answer 20

Substrate-level phosphorylation to give GTP:
Succinyl-CoA synthetase converts succinyl-CoA to succinate
gives phosphate group to GDP to form GTP (GTP to ATP is realatively simple and just involves transfering the phosphate to ADP using the enzyme nucleoside diphosphokinase)

Question 21

CAC

Step 6:

Answer 21

Dehydrogenation to give reduced FADH2:
oxidation of succinate is catalyzed by succinate dehydrogenase to form fumarate
Formation from a single C-C bond to a trans double C-C bond.
also forms FADH2

enam is part of complex II in ETC

Question 22

CAC

Step 7:

Answer 22

Hydration:
catalyzed by Fumarase. Hydrates the double bond to produce a single bond Malate

Question 23

CAC

Step 8:

Answer 23

Dehydrogenation to give NADH:
Malate dehydrogenase reforms the oxaloacetate by oxidizing the secondary OH of Malate to a ketone
final step of cycle
forms 3rd and final NADH

Question 24

Regulation of CAC

What is the CAC activated by?

Answer 24

Substrate Availability

NAD and AMP

Question 25

Regulation of CAC

What is the CAC inhibited by?

Answer 25

product accumulation

NADH and ATP

Question 26

Regulation of CAC

Which enzymes regulate rate-limited steps?

Answer 26

Citrate Synthase: ATP, NADH, and succinyl-CoA inhibit

Isocitrate dehydrogenase: ATP inhibits, ADP and NAD activate

a-Ketoglutarate dehydrogenase: NADH and succinyl-CoS inhibit, AMP activates

Question 27

Plants/bacteria

What cycle do plants and some bacteria have similar to CAC?

Answer 27

Glyoxylate Cycle

Question 28

Plants/Bacteria

What are the differences in Glycoxylate cycle and CAC?

Answer 28

Glycoxylate skips the decarboxylation of CAC to form glycoxylate

Also has 2 new enams, isocitrate lyase and malate synthase