598
THE ORGANIC CHEMISTRY OF INTERMEDIARY METABOLISM
Box 15.2 (continued)
code, many natural peptides are known to be synthesized by a more individualistic sequence of enzyme-controlled
processes, in which each amino acid is added as a result of the specificity of the enzyme involved. The many
stages of the whole process appear to be carried out by a multi-functional enzyme termed a non-ribosomal
peptide synthase (see Section 13.5.2). Pantothenic acid bound to the enzyme as pantotheine is used to carry the
growing peptide chain through its thiol group. The long ‘pantotheinyl arm’ allows different active sites on the
enzyme to be reached in the chain assembly process, a process remarkably analogous to the fatty acid synthase
mechanism.
15.6 Amino acids and transamination
The synthesis of amino acids depends upon the amination of the Krebs cycle intermediate 2-oxoglutarate
to glutamate, a process of reductive amination. This
can occur when a high concentration of ammonium
ions is available and involves NADH or NADPH as
reducing agent.
C O
2-oxoglutarate
glutamate
C NH
NH 3
NAD(P)H
H 2 O
NAD(P)
+
glutamate
dehydrogenase
this involves formation and reduction of an intermediate imine
NAD(P)H
HO 2 C
HO 2 C
O
HO 2 C
HO 2 C
NH 2
H
CH NH 2
NH 3
The reaction involves formation of an imine
through reaction of ammonia with the ketone, followed by reduction of this imine (see Section 7.7.1).
As we noted earlier (see Section 15.1.1), nicotinamide coenzymes may also participate in imine
reductions as well as aldehyde/ketone reductions, further emphasizing the imine–carbonyl analogy (see
Section 7.7.1). The reverse reaction, removal of
ammonia from glutamate, is also of importance in
amino acid catabolism.
Glutamate can then participate in the formation of
other amino acids via the process called transamination. Transamination is the exchange of the amino
group from an amino acid to a keto acid, and provides the most common process for the introduction
of nitrogen into amino acids, and for the removal of
nitrogen from them. The reaction is catalysed by a
transaminase enzyme, and the coenzyme pyridoxal
phosphate (PLP) is required.
N
CHO
OH
CH 3
PO
2-oxoglutarate
glutamate
a transaminase
coenzyme pyridoxal phosphate involved
pyridoxal P
(PLP)
keto acid
amino acid
HO 2 C
HO 2 C
NH 2
H
HO 2 C
HO 2 C
O
O
R
HO 2 C
HO 2 C
R
NH 2
H
THE ORGANIC CHEMISTRY OF INTERMEDIARY METABOLISM
Box 15.2 (continued)
code, many natural peptides are known to be synthesized by a more individualistic sequence of enzyme-controlled
processes, in which each amino acid is added as a result of the specificity of the enzyme involved. The many
stages of the whole process appear to be carried out by a multi-functional enzyme termed a non-ribosomal
peptide synthase (see Section 13.5.2). Pantothenic acid bound to the enzyme as pantotheine is used to carry the
growing peptide chain through its thiol group. The long ‘pantotheinyl arm’ allows different active sites on the
enzyme to be reached in the chain assembly process, a process remarkably analogous to the fatty acid synthase
mechanism.
15.6 Amino acids and transamination
The synthesis of amino acids depends upon the amination of the Krebs cycle intermediate 2-oxoglutarate
to glutamate, a process of reductive amination. This
can occur when a high concentration of ammonium
ions is available and involves NADH or NADPH as
reducing agent.
C O
2-oxoglutarate
glutamate
C NH
NH 3
NAD(P)H
H 2 O
NAD(P)
+
glutamate
dehydrogenase
this involves formation and reduction of an intermediate imine
NAD(P)H
HO 2 C
HO 2 C
O
HO 2 C
HO 2 C
NH 2
H
CH NH 2
NH 3
The reaction involves formation of an imine
through reaction of ammonia with the ketone, followed by reduction of this imine (see Section 7.7.1).
As we noted earlier (see Section 15.1.1), nicotinamide coenzymes may also participate in imine
reductions as well as aldehyde/ketone reductions, further emphasizing the imine–carbonyl analogy (see
Section 7.7.1). The reverse reaction, removal of
ammonia from glutamate, is also of importance in
amino acid catabolism.
Glutamate can then participate in the formation of
other amino acids via the process called transamination. Transamination is the exchange of the amino
group from an amino acid to a keto acid, and provides the most common process for the introduction
of nitrogen into amino acids, and for the removal of
nitrogen from them. The reaction is catalysed by a
transaminase enzyme, and the coenzyme pyridoxal
phosphate (PLP) is required.
N
CHO
OH
CH 3
PO
2-oxoglutarate
glutamate
a transaminase
coenzyme pyridoxal phosphate involved
pyridoxal P
(PLP)
keto acid
amino acid
HO 2 C
HO 2 C
NH 2
H
HO 2 C
HO 2 C
O
O
R
HO 2 C
HO 2 C
R
NH 2
H