TRICARBOXYLIC ACID CYCLE

DENTAL BIOCHEMISTRY 2015LECTURE 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 Activator

PyruvateDH ATP

NADH

Acetyl CoA

Citrate synthase ATP

IsocitrateDH ATP ADP

NADH

α-Ketoglutarat e DH NADH

Succiny l CoA

LECTURE OBJECTIVES

• 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.