Organic Chemistry 4 th Edition Paula Yurkanis Bruice Chapter 25 The Organic Mechanisms of the Coenzymes Metabolism Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall

catabolism: complex molecules simple molecules + energy anabolism: simple molecules + energy complex molecules Overall View of Metabolism

The Four Stages of Catabolism

The coenzymes most commonly used by enzymes to catalyze redox reactions: oxidizing agents reducing agents

The Components of NAD +

Oxidation of an Alcohol by NAD +

Reduction by NADH

All the chemistry of the pyridine nucleotide coenzymes takes place at the 4-position of the pyridine ring

The Mechanism of Reduction by NADH (or NADPH)

A reducing enzyme can distinguish between the two hydrogens at the 4-position of the nicotinamide ring

Another set of coenzymes in redox reactions

Mechanisms for Flavin Nucleotide Coenzymes

Unlike NADH, FADH 2 does not dissociate from the enzyme

The Coenzyme Form of Vitamin B 1

Consider this reaction …

Biotin: Vitamin H

In addition to requiring bicarbonate, biotin-requiring enzymes require Mg 2+ and ATP

Pyridoxal Phosphate: Vitamin B 6 Required by enzymes that catalyze certain transformations of amino acids

In each of these transformations, one of the bonds to the  -carbon of the amino acid substrate is broken in the first step of the reaction

In the PLP-dependent reactions, the bond cleaved in the first step of the reaction depends on the conformation of the amino acid that the enzyme binds

Enzymes that catalyze certain rearrangement reactions require coenzyme B 12

Tetrahydrofolate is the coenzyme required by enzymes that catalyze the transfer of a group containing one carbon to their substrates

The Six Different THF-Coenzymes

The Enzyme that Converts U’s into T’s

Conversion of Dihydrofolate Back to N 5, N 10 -Methylene-THF

5-Fluorouracil is a mechanistic-based inhibitor of thymidylate synthase used in cancer chemotherapy

Aminopterin and methotrexate competitively inhibit dihydrofolate reductase and are used as anticancer drugs

Vitamin K is required for proper clotting of blood

Regeneration of Vitamin KH 2