Pyruvate Metabolism & Citric Acid Cycle

Question 1

Where does the metabolism of pyruvate take place?

Answer 1

• in the mitochondria
• (glucose to pyruvate is in the cytoplasm)
• (pyruvate to acetyl-CoA or to oxaloactetate is in the mitochondria)

Question 2

Which enzyme converts pyruvate into __________? What regulates this reaction? What does the enzyme need to function?

Answer 2

• pyruvate dehydrogenase (PDH) makes acetyl-CoA + CO2 + NADH from pyruvate
• PDH is inhibited by its product, acetyl-CoA
• PDH requires “Tender Loving Care From Nancy” to function (thiamine pyrophasphate [TPP] from B1/thiamine, lipoic acid, CoA from B5/pantothenate, FAD from B2/riboflavin, NAD from B3/niacin)

Question 3

Which three enzymes require “Tender Loving Care From Nancy” to function?

Answer 3

• pyruvate dehydrogenase (PDH): pyruvate into acteyl-CoA
• alpha-ketoglutarate dehydrogenase: alpha-ketoglutarate into succinyl-CoA
• branched chain ketoacid dehydrogenase

Question 4

Why can alcoholic patients die when given IV glucose?

Answer 4

• alcoholics are often thiamine deficient because alcohol decreases its absorption from foods
• this prevents pyruvate dehydrogenase (PDH) from functioning properly because of a lack of thiamine pyrophosphate (TPP)
• pyruvate builds up as a result, eventually being converted to lactate = massive and rapid onset of lactic acidosis

Question 5

How much energy does the conversion of pyruvate into acetyl-CoA generate?

Answer 5

• 1 NADH, so 3 ATP

- (remember that each glucose will yield 2 pyruvate, so each glucose will generate 6 ATP from this step)

Question 6

What happens to acteyl-CoA? How much energy will be generated from this next step in metabolism?

Answer 6

• it enters the citric acid cycle/Kreb cycle/TCA cycle

- each acteyl-CoA will generate 12 ATP (so each glucose will generate 24 ATP)

Question 7

List the molecules involved in the citric acid cycle.

Answer 7

• “Citrate Is Kreb’s Starting Substrate For Making Oxaloacetate”
• citrate –> isocitrate –> alpha-ketoglutarate –> succinyl-CoA –> succinate –> fumarate –> malate –> oxaloactetate

Question 8

Which molecules and enzyme are involved in forming citrate?

Answer 8

• citrate synthase joins acetyl-CoA (2C) with oxaloacetate (4C) to form the 6-carbon molecule citrate

Question 9

Which enzyme converts isocitrate into _____________? What regulates this reaction?

Answer 9

• isocitrate dehydrogenase makes alpha-ketoglutarate (5C) + NADH + CO2
• the enzyme is inhibited by ATP and NADH (this creates a build up of citrate, which is used to inhibit glycolysis by inhibiting PFK-1)

Question 10

Which enzyme converts alpha-ketogluratate into _____________? What does this enzyme need to function?

Answer 10

• alpha-ketoglutarate dehydrogenase makes succinyl-CoA (4C) + NADH + CO2
• this enzyme requires “Tender Loving Care From Nancy” to function (TPP [B1], lipoic acid, CoA [B5], FAD [B2], NAD [B3])

Question 11

What does the conversion of succinyl-CoA into succinate form? What type of reaction is this?

Answer 11

• succinyl-CoA –> succinate + CoA + GTP
• this is a substrate level phosphorylation reaction (it is the 3rd of 3; the other 2: 1,3-bisphosphoglycerate into 3-phosphoglycerate and phosphoenolpyruvate into pyruvate)

Question 12

What is unique about the enzyme that converts succinate into fumarate? What does this reaction generate?

Answer 12

• the enzyme is succinate dehydrogenase and it is also found in the ETC where it is known as complex II
• this reaction generates FADH2 (FADH2 generates 2 ATP in the ETC)

Question 13

What does the conversion of malate into oxaloacetate generate?

Answer 13

• this reaction generates NADH

Question 14

Each acetyl-CoA generates 12 ATP from the citric acid cycle - explain where they are coming from.

Answer 14

• isocitrate to alpha-KG generates NADH (3 ATP)
• alpha-KG to succinyl-CoA generates NADH
• succinyl-CoA to succinate generates GTP (1 ATP)
• succinate to fumarate generates FADH2 (2 ATP)
• malate to oxaloacetate generates NADH
• 3 NADH + 1 GTP + 1 FADH2 = 12 ATP