PDH & Citric Acid Cycle

Question 1

Pyruvate Dehydrogenase Complex

Answer 1

Enzymes, Coenzymes, and proteins associated with the formation of Acetyl CoA from Pyruvate.

Enzymes: pyruvate dehydrogenase, dihydrolipoyl dehydrogenase, dihydrolipoyl transacetylase

Regulatory Proteins: protein kinase, protein phosphatase

Coenzymes: CoASH, FAD, NAD+, Thiamine pyrophosphate (TPP), Lipoic Acid

Question 2

Coenzyme A

Answer 2

derived from B5

Acetyl group attached at the terminal SH forming a thioester group

Question 3

Vitamin derivatives in PDH

Answer 3

B2 - FAD
B3 - NAD+
B5 - Coenzyme A
B1 (Thiamine) - TPP
B12 (Cobalamin) - succinyl CoA can come from a pathway dependent on Cobalamin

Question 4

Activators of PDH

Answer 4

Dephosphorylation
Insulin in adipocytes and Liver
Catecholamines in cardiac muscle
Ca++ in skeletal muscle
Mg++

Ca++ and Mg++ activate PDH phosphatase activating the Pyruvate dehydrogenase

Question 5

Inhibitors of PDH

Answer 5

phosphorylation
•Acetyl CoA
•ATP
•NADH

PDH Kinase phosphorylates Ser and Thr residues of pyruvate dehydrogenase

Question 6

Citrate Synthase

Answer 6

Formation of 6C citrate from Acetyl CoA and Oxalocetate

Irreversible reaction

regulated enzyme in TCA

Activated by substrate availability, Ca++, ADP
Inhibited by ATP, NADH, Succinyl CoA, Fatty Acyl CoA

Question 7

Aconitase

Answer 7

Formation of Isocitrate from citrate (reversible)

Question 8

Isocitrate deydrogenase

Answer 8

Formation of Alpha-Ketoglutarate and NADH from Isocitrate and NAD+.

Releases CO2

Inhibited by ATP and NADH
Activated by ADP and Ca++

Irreversible reaction

Question 9

Alpha-Ketogluterate Dehydrogenase Complex

Answer 9

Similar to PDH complex

Forms Succinyl CoA and NADH from Alpha-Ketogluterate and NAD+

Releases CO2

Activated by Ca++
Inhibited by ATP, GTP, NADH, Succinyl CoA

Question 10

Succinate Thiokinase

Answer 10

Forms Succinate and GTP from Succinyl CoA and GDP + Pi

Question 11

Succinate Dehydrogenase

Answer 11

Forms Fumarate and FADH2 from succinate and FAD

regulated enzyme in TCA

Activated by ADP, Pi and Succinate
Inhibited by OAA

Question 12

Fumarase

Answer 12

Forms Malate from fumarate

Question 13

Malate Dehydrogenase

Answer 13

Forms Oxaloacetate and NADH from malate and NAD+

Question 14

Pyruvate Dehydrogenase Deficiency

Answer 14

Metabolic effect:
Increase in pyruvate with concomitant increse in lactic acid and alanine (via transamination), decrease in production of acetyl CoA; severe reduction in ATP production

Clinical features:
lactic acidosis, neurologic defects, myopathy; usually fatal at early age

Question 15

Arsenic poisoning

Answer 15

Arsenic poisoning results from its binding to lipoic acid which is needed for the activity of dihydrolipoyl transacetylase

●Results in lactic acidosis, neurological defects, brain particularly, can lead to death

●Arsenic also affects other lipoic acid requiring enzymes such as α–ketoglutarate DH and branched chain α–ketoacid DH