Biochem - Metabolism (Pyruvate metabolism & TCA cycle)

Question 1

What is the purpose of the pyruvate dehydrogenase complex?

Answer 1

Mitochondrial enzyme complex linking glycolysis and TCA cycle

Question 2

In what states is pyruvate dehydrogenase complex differentially regulated? In which of these is it active?

Answer 2

Differentially regulated in fed/fasting states (active in fed state).

Question 3

What is the reaction catalyzed by pyruvate dehydrogenase complex?

Answer 3

Reaction: Pyruvate + NAD+ + CoA => Acetyl-CoA + CO2 + NADH

Question 4

How many enzymes does the pyruvate dehydrogenase complex contain? What 5 cofactors do they require?

Answer 4

The complex contains 3 enzymes that require 5 cofactors: (1) Pyrophosphate (B1, thiamine; TPP) (2) FAD (B2, riboflavin) (3) NAD (B3, niacin) (4) CoA (B5, pantothenate) (5) Lipoic acid

Question 5

What physiological process/activity activates pyruvate dehydrogenase complex? What are 3 effects of this physiological process/activity?

Answer 5

Activated by exercise, which: (1) Increase NAD+/NADH ratio (2) Increase ADP (3) Increase Ca2+

Question 6

To what other metabolic complex is pyruvate dehydrogenase complex similar, and how so? What reaction does this other complex catalyze?

Answer 6

The complex is similar to the alpha-ketoglutarate dehydrogenase complex (same cofactors, similar substrate and action), which converts alpha-ketoglutarate => succinyl-CoA (TCA cycle)

Question 7

How does Arsenic impact the activity of the pyruvate dehydrogenase complex?

Answer 7

Arsenic inhibits lipoic acid (a cofactor required for pyruvate dehydrogenase complex)

Question 8

What are 3 findings associated with Arsenic poisoning? Again, how does Arsenic impact the activity of the pyruvate dehydrogenase complex?

Answer 8

Arsenic inhibits lipoic acid (a cofactor required for pyruvate dehydrogenase complex); Findings: vomiting, rice-water stools, garlic breath

Question 9

What metabolic defect(s) occur(s) due to pyruvate dehydrogenase complex deficiency?

Answer 9

Causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT)

Question 10

What are the only 2 purely ketogenic amino acids?

Answer 10

Lysine and Leucine - the onLy pureLy ketogenic amino acids

Question 11

What are 3 clinical findings associated with pyruvate dehydrogenase complex deficiency?

Answer 11

(1) Neurological defects (2) Lactic acidosis (3) Increase serum alanine starting in infancy

Question 12

What is the treatment for pyruvate dehydrogenase complex deficiency?

Answer 12

Increase intake of ketogenic nutrients (e.g., high fat content or high lysine and leucine)

Question 13

What are 4 different pyruvate metabolic pathways?

Answer 13

(1) Alanine aminotransferase (2) Pyruvate carboxylase (3) Pyruvate dehydrogenase (4) Lactic acid dehydrogenase

Question 14

What kind of metabolic pathway is Alanine aminotransferase? What is its associated cofactor and function?

Answer 14

Pyruvate metabolic pathway; Alanine aminotransferase (B6): alanine carries amino groups to the liver from muscle

Question 15

What kind of metabolic pathway is Pyruvate carboxylase? What is its associated cofactor and function?

Answer 15

Pyruvate metabolic pathway; Pyruvate carboxylase (biotin): oxaloacetate can replenish TCA cycle or can be used in gluconeogesis

Question 16

What kind of metabolic pathway is Pyruvate dehydrogenase? What is its associated cofactor and function?

Answer 16

Pyruvate metabolic pathway; Pyruvate dehydrogenase (B1, B2, B3, B5, lipoic acid): transition from glycolysis to the TCA cycle

Question 17

What kind of metabolic pathway is Lactic acid dehydrogenase? What is its associated cofactor and function?

Answer 17

Pyruvate metabolic pathway; Lactic acid dehydrogenase (B3): end of anaerobic glycolysis (major pathway in RBCs, leukocytes, kidney medulla, lens, testes, and cornea)

Question 18

What enzyme complex serves as the end of anaerobic glycolysis? What are 6 parts of the body in which this is the major pathway?

Answer 18

Lactic acid dehydrogenase (B3): end of anaerobic glycolysis (major pathway in RBCs, leukocytes, kidney medulla, lens, testes, and cornea)

Question 19

Draw the 4 different pathways of pyruvate metabolism, showing the major cofactors of each.

Answer 19

See p. 103 in First Aid 2014 for visual at middle of page

Question 20

What is another name for the TCA cycle?

Answer 20

TCA Cycle (Krebs cycle)

Question 21

What is the initial step leading into the TCA cycle? What is produced from this step?

Answer 21

Pyruvate => Acetyl-CoA produces 1 NADH, 1 CO2

Question 22

What does the TCA cycle produce? Clarify what is produced per acetyl-CoA versus per glucose.

Answer 22

The TCA cycle produces 3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl-CoA = 10 ATP/ acetyl-CoA (2 x everything per glucose).

Question 23

Where do TCA cycle reactions occur?

Answer 23

TCA cycle reactions occur in the mitochondria

Question 24

Again, what other complex is similar to pyruvate dehydrogenase complex, and how so?

Answer 24

Alpha-ketoglutarate dehydrogenase complex requires the same cofactors as the pyruvate dehydrogenase complex (B1, B2, B3, B5, lipoic acid).

Question 25

What are the 8 major substrates of the TCA cycle (in order of first to last)?

Answer 25

(1) Citrate (2) Isocitrate (3) alpha-ketoglutarate (4) Succinyl-CoA (5) Succinate (6) Fumarate (7) Malate (8) Oxaloacetate; think: “Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate”

Question 26

Draw the TCA cycle, including major substrates, enzymes, and regulators. Also, note irreversible enzymes with an asterisk.

Answer 26

See p. 103 in First Aid 2014 for visual at bottom of page