section
6.6
Mechanisms of Enzyme Action
107
two-substrate reactions, being bound only momentarily to
the enzyme during catalysis. They are chemically altered
during the reaction and are reconverted to their original
forms by the same or another enzyme (e.g., NAD+- or
NADP+-dependent dehydrogenase reactions). Prosthetic
groups form part of the active center and undergo cyclic
chemical changes during the reaction (e.g., pyridoxal
phosphate in aminotransferases). Principal coenzymes,
prosthetic groups, and cofactors are listed below. Their
metabolic roles are discussed elsewhere, e.g., with the
reactions they catalyze and the vitamins from which they
are derived.
1. Compounds involved in H-transfer reactions and
derived from vitamin precursors.
a.
N ico tin a m id e a d en in e d in u cleo tid e
(NAD+), also
known as diphosphopyridine nucleotide (DPN+).
The reduced form is NADH (DPNH).
b.
N ico tin a m id e a d en in e d in u cleo tid e p h o sp h a te
(NADP+), also known as triphosphopyridine
nucleotide (TPN+). The reduced form is NADPH
(TPNH).
These compounds are derived from the vitamin
niacin (nicotinic acid, nicotinamide) and require it
for their synthesis. Small amounts of niacin are
derived from the essential amino acid tryptophan.
c.
F lavin m o n o n u cleo tid e
(FMN). The reduced form
is FMNH2.
d.
F lavin a d en in e d in u cleo tid e
(FAD). The reduced
form is FADH2.
These compounds are derived from the vitamin
riboflavin. They are not true nucleotides, because
the flavin ring system is attached to ribitol, a sugar
alcohol, rather than ribose.
2. Compounds involved in H-transfer reactions and
derived from nonvitamin precursors.
a.
L ip o ic a c id
apparently can be synthesized in
sufficient quantity by humans. It is also involved in
acyl group transfer during oxidative
decarboxylation of a-keto acids.
b.
B io p terin
(a pteridine-containing compound)
participates in certain hydroxylase reactions (e.g.,
phenylalanine hydroxylase).
c.
C oen zym e Q
(CoQ, ubiquinone) is a group
of closely related compounds differing only in the
length of the side chain. They can be synthesized
in humans from farnesyl pyrophosphate, an
intermediate in cholesterol biosynthesis. Although
the structure of coenzyme Q is similar to that of vi-
tamin Ki, no interrelationship has been established.
3. Compounds involved in group transfer reactions and
derived from vitamin precursors.
a.
C oen zym e A
(CoA, CoASH) takes part in acetyl
and other acyl group transferase and requires the
vitamin pantothenic acid for its synthesis.
b.
T h iam in e p yro p h o sp h a te
(TPP, cocarboxylase) is
used for oxidative decarboxylation of a-keto acids
and in the transketolase-catalyzed steps of the
pentose phosphate pathway. It is derived from
thiamine (vitamin B i ).
c.
P yrid o x a l p h o sp h a te
is a cofactor for a wide
variety of types of reactions on amino acids,
namely, racemization, decarboxylation,
transamination, elimination of water or hydrogen
sulfide. It is derived from pyridoxine, pyridoxal,
and pyridoxamine (collectively called
vitamin B6).
d.
T etrah ydrofolic a c id
(FH
4
) is a carrier of
one-carbon fragments such as formyl, methylene,
methyl, and formimino groups. It is derived from
folic acid (folacin).
e.
B io tin
is vitamin tightly bound to the apoenzyme
in an amide linkage to the s -ami no group of a
lysyl residue and involved in carboxylation
reactions.
f.
C o b a m id e co en zym e
(5,6-dimethylbenzimidazole
cobamide 5'-dehydroadenosyl cobalamine)
contains cobalt bound in a porphyrin-like ring
system and is unusual in that it contains a
cobalt-carbon (organometallic) bond. It is
involved in methyl-transfer reactions and
participates in the
1 , 2
shift of a hydrogen atom
accompanied by a
2
,
1
-shift of an alkyl, carboxyl,
hydroxyl, or amino group. Very small amounts,
derived from cyanocobalamin (vitamin Bj2), are
required by the body.
g.
V itam in K
participates in carboxylation reactions
of glutamic acid residues of some proteins
involved in blood coagulation and its regulation to
yield
y
-carboxyglutamic acid residues required for
Ca2+ binding. The vitamins K are derived from
naphthoquinones with isoprenoid side chains of
varying lengths.
h.
V itam in C
participates as a cofactor in the
hydroxylation reactions of proline and lysine of
collagen.
4. Compounds involved in group transfer reactions and
derived from nonvitamin precursors.
a.
A d en o sin e trip h o sp h a te
(ATP) can be a donor of
phosphate, adenosine, and adenosine
monophosphate (AMP) for various purposes. The
exergonic hydrolysis reaction of ATP provides the
energy for driving thermodynamically unfavorable
reactions.
