SM5

Question 1

How is Acetyl-CoA made available for the TCA cycle?

Answer 1

oxidation of FA like palmitate, ketone bodies like acetoacetate, monosaccharides like glucose, AA and ethanol. Pyruvate can be derived from glucose and amino acids like alanine.

Question 2

What 5 cofactors do alpha ketoacid dehydognases like pyruvate DH use?

Answer 2

1. thiamine pyrophosphate (vitamin B1)
2. lipoate
3. coenzyme A (from pantothenic acid, vitamin B5)
4. FAD (from riboflavin, vitamin B2)
5. NAD (from niacin, vitamin B3)

Question 3

When is pyruvate DH inhibited?

Answer 3

when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA.

Question 4

What reaction does Pyruvate DH catalyze?

Answer 4

It catalyzes the removal of carbon as Co2 to produce acetyl-CoA (2 carbons). As a result we capture some electrons as NADH. These will go to ETC.

Question 5

How is pyruvate DH regulated?

Answer 5

A specific pyruvate dehydrogenase kinase (PDK) deactivates it by phosphorylation. Pyruvate dehydrogenase phosphatase (PDP), activates it by dephosphorylation.

Question 6

What would result from PDC deficiency due to mutations in any of the subunits?

Answer 6

lactic acidosis.

Question 7

Why is the concentration of citrate in the mitochondria normally kept high?

Answer 7

Because in the TCA cycle the formation of citrate from OAA has a large negative free energy and is favored and the conversion of isocitrate from citrate has a positive free energy change favoring formation of citrate.

Question 8

In the reaction converting malate to OAA which direction is favored.

Answer 8

+free energy, favoring formation of malate

Question 9

why is the concentration of OAA kept low?

Answer 9

It is another way of regulating the cycle because you can allow acetyl coA into the cycle if there is enough OAA to accept it.

Question 10

Which reactions in the TCA cycle are irreversible?

Answer 10

The formation of alphaketoglutarate from isocitrate and the formation of the activated succinyl CoA from alphaketoglutarate

Question 11

What is the rate limiting enzyme in the TCA cycle?

Answer 11

isocitrate dehydrogenase. Which is allosterically activated by ADP (finely tuned) and inhibited by NADH. It is physiologically irreversible, catalyzes a reaction with a large negative free energy and its product is rapidly removed (the succinyl coA). it is unregulated by CA2+.

Question 12

What are the three places inhibited by NADH?

Answer 12

isocitrate dehydrogenase (allosterically). alpha ketoglutarate DH, and malate DH

Question 13

Intermediates from TCA cycle can be used for many biosynthetic functions. This can deplete carbon from the cycle and OAA levels will drop. What must the cell do to compensate for this?

Answer 13

Anaplerotic reactions. We do this by removing the nitrogen from AA and using their carbon skeletons

a. Amino acids that form oxaloacetate
		i. asparagine
		ii. aspartate
b. Amino acids that form α-ketoglutarate
		i. glutamate
		ii. proline
		iii. arginine
		iv. histidine
c. Amino acids that form fumarate
		i. phenylalanine and tyrosine
d. Amino acids that form succinyl CoA
		i. methionine and S-adenosylmethionine (SAM)
		ii. valine and isoleucine
		iii. threonine
e. Amino acids that form acetyl CoA or acetoacetyl CoA
		i. leucine
		ii. isoleucine
		iii. lysine
                    iv. tryptophan

Question 14

When you get pyruvate from AA how do you convert it to OAA in the anaplerotic reaction:

Answer 14

biotin carries CO2 to attach it to the pyruvate. catalyzed by pyruvate carboxylase activated by Acetyl CoA

Question 15

Why do tumor cells need non-essential amino acids?

Answer 15

To make nucleic acids and cell membranes so cells can divide.