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TRICARBOXYLIC ACID
CYCLE
DENTAL BIOCHEMISTRY 2015
LECTURE 12
Michael Lea
LECTURE OUTLINE
• The tricarboxylic acid cycle (Krebs cycle, citric
acid cycle) is a focal end point for the
oxidation of carbohydrate, fat and amino
acids via acetyl coenzyme A.
• Pyruvate is converted to acetyl coenzyme A
by the pyruvate dehydrogenase complex.
• The reactions of the TCA cycle generate
carbon dioxide, reduced NAD, reduced FAD
and GTP
• There are negative and positive controls for
the TCA cycle
SUGGESTED READING
• Lippincott’s Biochemistry, 6th edition,
pages 109-115
Succinyl CoA synthetase
Fumarate hydratase
COMPETING REACTIONS
• Intermediate compounds in glycolysis
and the TCA cycle can be used in many
metabolic pathways
• Diversion of intermediates creates a
need for reactions that will maintain the
level of oxaloacetate.
ANAPLEROSIS (filling up)
• One of the most important reactions for
the production of oxaloacetate is the
reaction catalyzed by pyruvate
carboxylase.
• High levels of pyruvate carboxylase for
gluconeogenesis occur in liver and
kidney but other cells have lower
activities of pyruvate carboxylase to
maintain the concentration of
oxaloacetate.
REGULATION OF PYRUVATE DEHYDROGENASE AND THE
TCA CYCLE
Enzyme
Inhibitor
PyruvateDH
ATP
NAD H
Acetyl CoA
Citrate synthase
ATP
IsocitrateDH
ATP
NAD H
-Ketoglutarate DH
NAD H
Succinyl CoA
Activator
ADP
LECTURE OBJECTIVES
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After studying this lecture material you should be able to
Regarding the tricarboxylic acid cycle 1.
describe the enzymes and cofactors for each reaction.
2.
recognize the regulated reactions and effectors.
3.
identify the location of the cycle enzymes in the cell.
Regarding the pyruvate dehydrogenase complex 1.
distinguish the subunits and cofactors of the complex.
2.
recognize the individual reactions catalyzed by the enzyme sub units.
3.
recognize the effecters of control of the complex.
Regarding the integration of the cycle in cell metabolism
1.
recognize the anapleurotic reaction that replenishes the cycle from
pyruvate.
2.
name the sources of acetyl CoA for the cycle.