AC Lecture 62: Fate of Pyruvate

Question 1

What are the possible fates of pyruvate in mammals?

Answer 1

1. reduced to lactic acid (lactate)
2. enter mitochondria for further metabolism by pyruvate dehydrogenase (PDH) to acetyl CoA
3. (liver only) metabolized to oxaloacetate by pyruvate carboxylase
4. (in RBC only) must be reduced to lactate

Question 2

What is the function of the alanine aminotransferase (ALT) pyruvate metabolic pathway?

Answer 2

alanine carries amino groups to the liver from muscle
alanine < – > pyruvate
via ALT

Question 3

What is the function of the pyruvate carboxylase (biotin) pyruvate metabolic pathway?

Answer 3

oxaloacetate can replenish the TCA cycle or be used in gluconeogenesis
pyruvate + CO2 + ATP < – > oxaloacetate
via pyruvate carboxylase

Question 4

What is the function of the pyruvate dehydrogenase (B1, B2, B3, B5, lipoic acid) pyruvate metabolic pathway?

Answer 4

transition from glycolysis to the TCA cycle
pyruvate + NAD+ – > acetyl-CoA + NADH + CO2
via PDH
*note it is irreversible

Question 5

What is the function of lactic acid dehydrogenase (B3) pyruvate metabolic pathway?

Answer 5

end of anaerobic glycolysis (major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea)
pyruvate + NADH < – > lactate + NAD+
via LDH

Question 6

Why is the LDH reaction critical to RBCs?

Answer 6

because RBCs do not have mitochondria so this is the only way they can get NADH reoxidized to NAD+ (which is necessary for glycolysis to continue at the glyceraldehyde 3-P dehydrogenase step)

Question 7

When is the LDH reaction most important?

Answer 7

when glycolysis is very rapid (e.g during muscle conraction, when insulin levels are high, or in tumor cells)

Question 8

What happens when lactic acid levels are high?

Answer 8

alter blood pH (lactic acidemia)
cramps (e.g. marathon runners)
aggravate gout

Question 9

What are the fates of lactate?

Answer 9

1. enters tissues to be reoxidized back to pyruvate

2. converted to glucose in the liver during gluconeogenesis

Question 10

What are the isoforms of LDH and where are they found?

Answer 10

H4 (brain or heart)
H3M (brain or heart)
H2M2
HM3 (RBCs and skeletal muscles)
M4 (RBCs and skeletal muscles)

Question 11

What are the properties of H and M subunits of LDH?

Answer 11

H subunits have higher affinity for lactate and NAD

high levels of pyruvate inhibit H4 (but not M4)

Question 12

How is ethanol metabolized in mammals?

Answer 12

ethanol + NAD+ –> acetaldehyde + NADH –> –> acetyl CoA

via liver alcohol dehydrogenase

Question 13

What enzymes compose the PDH complex?

Answer 13

E1
E2
E3
PDH kinase
PDH phosphorylase

Question 14

What are the cofactors involved in the PDH reaction?

Answer 14

TPP (for E1)
lipoic acid (for E2)
riboflavin (for E3)
phosphopantetheine (for CoASH)
niacin (for NAD+)

Question 15

What inhibits each of the enzymes in the PDH complex?

Answer 15

E1: ATP, phosphorylation by PDH kinase
E2: acetyl CoA (its product)
E3: NADH (its product)

Question 16

What activates the E1 enzyme in the PDH compex?

Answer 16

dephosphorylation by PDH phosphatase (which is increased by insulin)