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Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 25
The Organic
Mechanisms of the
Coenzymes
Metabolism
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall
Overall View of Metabolism
catabolism: complex molecules
simple molecules + energy
anabolism: simple molecules + energy
complex molecules
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, FADH2 does not dissociate from the
enzyme
The Coenzyme Form of Vitamin B1
Consider this reaction …
Biotin: Vitamin H
In addition to requiring bicarbonate, biotin-requiring
enzymes require Mg2+ and ATP
Pyridoxal Phosphate: Vitamin B6
Required by enzymes that catalyze certain
transformations of amino acids
In each of these transformations, one of the bonds to the
a-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 B12
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
N5, N10-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 KH2