Bio 27 PDHC & TCA Cycle

Question 1

What three directions can Pyruvate take and what enzymes catalyze those reactions?

Answer 1

Pyruvate–>Acetyl-CoA (PDHC (Pyruvate Dehydrogenase))
Pyruvate–>OAA (Pyruvate Carboxylase)
Pyruvate–>Lactate (Lactate Dehydrogenase)

Question 2

What is another name for vitamin B1?

Answer 2

Thiamine

Question 3

Another name for vitamin B2?

Answer 3

Riboflavin

Question 4

Another name for vitamin B5?

Answer 4

Pantothenate

Question 5

Another name for vitamin B3?

Answer 5

Niacin

Question 6

What is a coenzyme?

Answer 6

A non-protein compound that is needed for the functioning of an enzyme.

Question 7

What are the 5 coenzymes for PDHC and their precursor vitamins?

Answer 7

TPP from Thiamine (B1)
FAD from Riboflavin (B2)
CoA from Pantothenate (B5)
NAD+ from Niacin (B3)
Lipoic Acid (has no vit. precursor)

Question 8

Why is the TCA cycle the final common pathway for fuel molecules?

Answer 8

Three main fuels are: carbs, protein, fats

All can be broken down to Acetyl-CoA and put into the TCA cycle to make NADH, FADH2 to be used for energy in the ETC.

Question 9

Explain the regulation of PDHC.

Answer 9

PDHC is covalently modified to affect its activity by PDH Kinase and PDH Phosphatase. Normal rule is followed here where dephosphorylation of PDHC allows it to go, and phosphorylation stops it.
PDH Kinase is activated by NADH, Acetyl CoA, and ATP
PDH Kinase is inactivated by Pyruvate
PDH Phosphatase is activated by increased Ca2+ levels

PDHC is also product inhibited by NADH and Acetyl-CoA

Question 10

If PDHC is inhibited and Pyruvate builds up, what will happen to the pyruvate?

Answer 10

If Pyruvate cannot be made into Acetyl-CoA, it will be shunted to Lactate or OAA.

Question 11

Do brain cells have mitochondria?

Answer 11

Yes. Brain cells use glucose for their energy, but they use it to run the TCA cycle and the ETC.

Question 12

What happens if an individual is deficient in PDHC?

Answer 12

Pyruvate cannot be converted to Acetyl-CoA, so glucose cannot be used to feed the TCA cycle or the ETC. Fatty acids must be used in the cells that can do so to produce Acetyl-CoA.
However, the brain mainly runs on glucose, so it is in trouble.

Question 13

Define amphibolic.

Answer 13

Describes the TCA cycle in that it does both anabolic and catabolic reactions.

Question 14

How is the TCA cycle regenerative?

Answer 14

Product becomes substrate for next reaction and is renewed with each complete cycle.

Question 15

What energy molecules are produced by TCA cycle?

Answer 15

One turn produces:
1 GTP
3 NADH
1 FADH2

Question 16

How is the TCA cycle affected by the I/G ratio?

Answer 16

It is unaffected by the I/G ratio, but it does often correspond with the fed or fasting state.

Question 17

What is the primary way that the TCA cycle is regulated?

Answer 17

The energy status of the cell largely determines how fast the cycle is running, and the amount of intermediate substrates can also influence the speed.

Question 18

Describe the production of citrate and its effect on other processes.

Answer 18

Citrate is produced as the first step of the TCA cycle where Acetyl-CoA and OAA come together to form citrate with the help of citrate synthase.
Irreversible reaction
Reaction is inhibited by the production of citrate.
Citrate inhibits PFK-1 and activate FA synthesis.

Question 19

Describe Isocitrate Dehydrogenase.

Answer 19

Converts Isocitrate into alpha-Ketoglutarate
Primary rate-limiting step for TCA, irreversible
Produces NADH
Allosterically inhibited by ATP & NADH
Allosterically activated by ADP & Ca2+

Question 20

Describe alpha-Ketoglutarate Dehydrogenase Complex.

Answer 20

alpha-Ketoglutarate--->Succinyl CoA
Complex of three enzymes
Has same 5 coenzymes as PDHC
Irreversible reaction
Produces NADH
Inhibited by products
Activated by Ca2+

Question 21

Explain TCA priming.

Answer 21

In order to speed up the TCA cycle, there must be more substrate available. Increasing Acetyl-CoA alone will not do it, OAA is needed to react with the acetyl-coa.
Pyruvate is turned into both with Pyruvate dehydrogenase and Pyruvate carboxylase. PDHC is inhibited by acetyl-coa and Pyruvate carboxylase is activated by acetyl-coa to direct pyruvate to produce more OAA and less acetyl-coa.

Question 22

Summarize the regulators of the TCA cycle.

Answer 22

PDHC: inhibited by acetyl CoA, NADH, ATP
Citrate Synthase: inhibited by Citrate
Isocitrate dehydrogenase: inhibited by NADH & ATP, activated by ADP
Alpha-KGDHC: inhibited by NADH

The high energy molecules inhibit the cycle. When energy is abundant, the cycle slows. When energy molecules are not abundant, the inhibition goes away and the cycle speeds up.

Question 23

What happens with thiamine deficiency?

Answer 23

Thiamine is a necessary coenzyme for PDHC, alpha-KGDH, and branch-chain ketoacid dehydrogenase. TCA cycle cannot run, and metabolism of branch-chain amino acids cannot happen to make energy for brain and muscle.
This causes aerobic dependent tissues to fail first. That would be the brain and cardiac muscle.

Question 24

What happens with arsenic poisoning?

Answer 24

It binds to Lipoic Acid and prevents it from being available for use with PDHC, alpha-KGDH, and branch-chain amino acid metabolism.