AC Lecture 63: Krebs Citric Acid Cycle

Question 1

What is the purpose of the TCA cycle?

Answer 1

extraction of most of the energy for cells

Question 2

Where does the TCA cycle occur?

Answer 2

the mitochondrial matrix compartment of all cells

Question 3

What is the net reaction of the TCA cycle?

Answer 3

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

Question 4

What is the first step of the TCA cycle?

Answer 4

Acetyl CoA + OAA –> citric acid

via citrate synthase

Question 5

What is the second step of the TCA cycle?

Answer 5

citric acid –> isocitrate

via aconitase

Question 6

What regulates citrate synthase?

Answer 6

inhibited by ATP and NADH

regulated by [OAA]

Question 7

What is the third step of the TCA cycle?

Answer 7

isocitrate + NAD+ –> alpha-ketogluterate + CO2 + NADH

via isocitrate dehydrogenase

Question 8

What is the rate limiting enzyme of the TCA cycle?

Answer 8

isocitrate dehydrogenase (step 3)

Question 9

What regulates isocitrate dehydrogense?

Answer 9

energy charge
stimulated by ADP (low energy)
inhibited by ATP and NADH (high energy charge)

Question 10

What is the fourth step in the TCA cycle?

Answer 10

alpha-ketogluterate + NAD+ + CoASH –> succinyl CoA + NADH + H+ + CO2
via alpha-KG dehydrogenase

Question 11

What is the function of the E1 subunit of alpha-KG dehydrogenase?

Answer 11

decarboxylase (plus cofactor thiamine PP)

decarboxylates alpha-KG to CO2 plus a four-carbon succinyl product

Question 12

What is the function of the E2 subunit of alpha-KG dehydrogenase?

Answer 12

uses lipoic acid to transfer the four-carbon succinyl product to the CoASH

Question 13

What is the function of the E3 subunit of alpha-KG dehydrogenase?

Answer 13

uses FAD and NAD to regenerate oxidized lipoic acid for E2

Question 14

What inhibits the activity of alpha-KG dehydrogenase?

Answer 14

E1: ATP
E2: succinyl CoA
E3: NADH

Question 15

What is step 5 of the TCA cycle?

Answer 15

succinyl CoA + GDP + Pi –> succinate + CoASH + GTP

via succinyl CoA synthase (thiokinase)

Question 16

Describe the last three steps of the TCA cycle.

Answer 16

designed to convert succinate to OAA

catalyzed by succinic dehydrogenase (producing FADH2), cumarase, and malate dehydrogenase (producing NADH)

Question 17

What is the overall yield of ATP from glucose to 6CO2?

Answer 17

Total 32
Glucose --> 2 pyruvate + 2NADH + 2 ATP
2NADH --> mito = 5 ATP
2 pyruvate --> 2 acetyl CoA + 2 NADH
2 NADH = 5 ATP
2 Acetyl CoA = 20 ATP

Question 18

What regulates the TCA cycle?

Answer 18

respiratory control (oxidation of NADH and FADH2)
energy charge (ATP inhibits multiple enzymes in the pathway)
concentration and regeneration of OAA

Question 19

What are anaplerotic reactions?

Answer 19

intermediates of a pathway (most often the TCA cycle) that can be diverted into other pathways or those that replenish the necessary substrates after they have been pulled out

Question 20

How can OAA be replenished?

Answer 20

pyruvate carboxylase reaction
amino acids catabolized to TCA cycle intermediates
PEPCK reaction

Question 21

What pathway can Succinyl CoA be diverted to?

Answer 21

heme synthesis

Question 22

What pathways can OAA be diverted to?

Answer 22

glucose
aspartate
asparagine
pyrimidines

Question 23

What pathways can citrate be diverted to?

Answer 23

fatty acid synthesis

Question 24

What pathways can alpha-KG be diverted to?

Answer 24

glutamate
glutamine
proline

Question 25

What amino acids can be catabolized to form TCA cycle intermediates?

Answer 25

glutamate –> alpha-KG
valine/isolucine/methionine/threonine/ –> succinyl CoA
phenyalanine/tyrosine –> fumarate
aspartate –> OAA