KREB CYCLE STRYER

CHE182
THE KREB CYCLE
OCCURS IN THE
MATRIX OF THE
MITOCHONDRIA
ACETYL CO A IS FORM FROM PYRUVATE

This irreversible reaction is the link between

glycolysis and the citric acid cycle.

It is catalyzed by Pyruvate Dehydrogenase and

coenzyme Thiamine Pyrophosphate (TPP)
ACETYL CO A IS FORM FROM PYRUVATE
 COENZYME A

Vitamin B5 is Panthothenate
VITAMIN B3 IS THE PRECURSOR OF NAD+
THIAMINE IS VITAMIN B1
 CITRATE SYNTHASE FORMS CITRATE
FROM OXALOACETATE AND ACETYL
COENZYME A
 SYNTHASE
An enzyme catalyzing a synthetic reaction in which two units
are joined without the direct participation of ATP.
CITRATE IS ISOMERIZED INTO ISOCITRATE

The enzyme is Aconitase.

Because cis-aconitate is an intermediate.
Dehydration then hydration.
 ISOCITRATE IS OXIDIZED AND
DECARBOXYLATED TO ΑLPHA-KETOGLUTARATE

The reaction is catalyzed by Isocitrate Dehydrogenase.

Oxalosuccinate is not stable and will spontaneously lost
CO2.
SUCCINYL COENZYME A IS FORMED BY
THE OXIDATIVE DECARBOXYLATION
OF ALPHA-KETOGLUTARATE

The enzyme is α-ketoglutarate Dehydrogenase.

A HIGH PHOSPHORYL-TRANSFER
POTENTIAL COMPOUND IS GENERATED
FROM SUCCINYL COENZYME A

1. The first reaction is catalyzed by Succinyl CoA Synthetase.

2. While the second reaction is catalyzed by nucleoside diphosphokinase.
3. The energy from Succinyl CoA bond is used to form GTP.
 OXALOACETATE IS REGENERATED
BY THE OXIDATION OF SUCCINATE

1. The series of reaction is similar to that of B-oxidation of fatty acid.

2. Oxidation, hydration and another oxidation.
3. Methylene group (CH2) is converted to carbonyl Carbon (C=O).
The enzymes are Succinate Dehydrogenase, Malate Dehydrogenase and
Fumarase.
 SUCCINATE DEHYDROGENASE

The formation of fumarate from succinate will not

liberate enough energy to form NADH from NAD+
thus the reaction utilized FAD.
FAD ARE FORMED FROM ATP AND
VITAMIN B2 RIBOFLAVIN
FUMARASE
MALATE DEHYDROGENASE
STOICHIOMETRY OF THE CITRIC ACID CYCLE
THE DISRUPTION OF PYRUVATE METABOLISM IS THE
CAUSE OF BERIBERI AND POISONING
BY MERCURY AND ARSENIC
• Beriberi means sheep. People who have beriberi walk like sheep.
• Beriberi is thiamine (vitamin B1 deficiency)
• Rice the staple food in the far east lacks thiamine.
• Mercury and Arsenic reacts with pyruvate dehydrogenase thus disabling the
enzyme.
• Hat maker in the medieval time uses mercury compound to soften the fur
used in making hat thus the phrase “mad as a hatter” in Alice in
Wonderland.
 BRITISH ANTI LEWISITE (BAL) DRUG

Lewisite an arsenic base chemical weapon in World War I.

 CHAPTER 17 STRYER END OF
CHAPTER QUESTION
Coenzymes. What coenzymes are required by
the pyruvate dehydrogenase complex? What
are their roles?
 CHAPTER 17 STRYER END OF
CHAPTER QUESTION
More coenzymes. Distinguish between catalytic
coenzymes and stoichiometric coenzymes in the
pyruvate dehydrogenase Complex.
CHAPTER 17 STRYER END OF
CHAPTER QUESTION
 CHAPTER 17 STRYER END OF
CHAPTER QUESTION
Lactic acidosis. Patients in shock often suffer from
lactic acidosis owing to a deficiency of O2. Why does
a lack of O2 lead to lactic acid accumulation? One
treatment for shock is to administer dichloroacetate,
which inhibits the kinase associated with the pyruvate
dehydrogenase complex. What is the biochemical
rationale for this treatment?
A decrease in the amount of O2 will necessitate an increase
in anaerobic glycolysis for energy production, leading to the
generation of a large amount of lactic acid. Under
conditions of shock, the kinase inhibitor is administered to
ensure that pyruvate dehydrogenase is operating maximally.
 CHAPTER 17 STRYER END OF
CHAPTER QUESTION
A nod is as good as a wink to a blind horse. Explain
why a GTP molecule, or another nucleoside
triphosphate, is energetically equivalent to an ATP
molecule in metabolism.
 CHAPTER 17 STRYER END OF
CHAPTER QUESTION
One from two. The synthesis of citrate from
acetyl CoA and oxaloacetate is a biosynthetic
reaction. What is the energy source that drives
formation of citrate?
The reaction is powered by the hydrolysis of a
thioester. Acetyl CoA provides the thioester that is
converted into citryl CoA. When this thioester is
hydrolyzed, citrate is formed in an irreversible
reaction.