Review 2- Citric Acid Cycle

Question 1

What are the starting materials and there processes that make the components that make Acetyl CoA?

Answer 1

Glycogen–>glycogenolysis-glucose-glycolysis–>pyruvate

Triglycerides–>lipolysis–>fatty acid

Protein–>proteolysis–>amino acid

Question 2

What does Acetyl CoA lead to?

Answer 2

1. Products of Citric Acid Cycle
2. ketone bodies
3. fatty acids; strerols

Question 3

What are the four products pyruvate can make?

Answer 3

1. Alanine (transamination)
2. OAA (carboxylation)
3. Lactate (reduction)
4. Acetyl CoA (oxidation)

Question 4

What turns pyruvate into Acetyl CoA? What cofactors does it need?

Answer 4

Pyruvate dehydrogenase (PDH) : E1, E2, E3
Cofactors: 
Thymine (TPP, B1)
Riboflavin (FAD, B2)
Niacin (NAD, B3)

Question 5

How is Pyruvate dehydrogenase deficiency inherited?

Answer 5

Most common: X-linked dominant-mutation of E1 alpha gene

Less common: autosomal recessive

Question 6

What levels are elevated in pyruvate dehydrogenase deficiency, and what do these elevations lead to? How can pyruvate dehydrogenase deficiency be treated?

Answer 6

Elevated serum levels of: Lactate, Pyruvate, and Alanine
–>chronic lactic acidosis

Treatment:

1. Dietary supplementation with: Thiamine, Carnitine, Lipoic Acids (these lead to Acetyl Co-A)
2. Dichloroacetate (inhibits protein kinase subunit of pyruvate dehyrogenase- stops the inactivity by stopping phosphorylation)

Question 7

How much ATP does the Citric Acid Cycle generate?

Answer 7

9 ATP & 1 GTP

(3 NADH2.5ATP/NADH)=7.5
(1 FADH 1.5 ATP/FADH)=1.5
(1 GTP–>1 ATP)=1
10 ATP total

Question 8

How is the citric acid cycle controlled by fine control?

Answer 8

Allosteric Regulation
1. Isocitrate Dehyrogenase 
(isocitrate-->alpha ketoglutarate)
Activator: ADP
Inhibitor: ATP and NADH

2. Alpha-Ketoglutarate Dehydrogenase
   (alpha ketoglutarate–> succinyl CoA)
   Activator: Ca2+
   Inhibitor: NADH, Succinyl CoA, ATP, GTP

Question 9

How is the citric acid cycle controlled by course control?

Answer 9

Low Oxygen–>increase in NADH and FADH2
-Lack of NAD+ and FAD will decreases CAC

High cellular activity—>decreased ATP and increased ADP
-Lack of ATP will increase CAC

Supply of Acetyl CoA (pyruvate dehydrogenase, carnitine, CAT1)
….High levels increase CAC

Oxaloacetate levels
-depleted by some biosynthetic pathways
-replenished by intermediate reactions that generate CAC intermediates
…low levels increase CAC?

Question 10

What can replace alpha Ketoglutarate

Answer 10

Glutamate

Question 11

What can replace Succinyl CoA

Answer 11

Propionyl CoA

Question 12

What can replace Fumarate

Answer 12

Amino Acids

Question 13

What can replace Oxaloacetate

Answer 13

Aspartate