Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

214 Chapter 9
– BEnz
CO −
2
Cl
H
NH + Cl
CO −
2
NH +
2− O 3 PO
OH
2− OH
O 3 PO 2− O 3 PO
+
N
H
N
Cl −
H
+
N
H
NH + CO 2
−
OH
displacement
by Lys-NH 2
2− O 3 PO
− O 2 C
O
Lys
NH
OH
+
N
H
+
NH 2
Lys
− O 2 C
NH
H 2 O
OH
2− O 3 PO
+
N
H
NH 2
− O 2 C
2− O 3 PO
+
N
H
Figure 9.4 Mechanism for inhibition of alanine racemase by b-chloro-d-alanine.
NH +
OH
Lys
corresponding primary amine. Reprotonation usually takes place with retention
of conWguration at the a-position, as shown in Figure 9.5. One important
example of a PLP-dependent decarboxylase is the mammalian 3,4-dihydroxyphenylalanine
(dopa) decarboxylase, which catalyses the decarboxylation of
3,4-dihydroxyphenylalanine to dopamine. Dopamine is a precursor to the
neurotransmitters epinephrine and norepinephrine. This enzyme also catalyses
the decarboxylation of 5-hydroxytryptophan to give another neurotransmitter
serotonin, as shown in Figure 9.6.
The third transformation carried out at the a-position of amino acids by
PLP-dependent enzymes is transamination: conversion of the a-amino acid to
an a-keto acid. This class of enzymes will be illustrated by the case study of
aspartate aminotransferase.
O − AEnz
H
D
− AEnz
R
R H
R
H O
D
NH +
NH + NH +
2− OH
O 3 PO 2− OH
O 3 PO 2− OH
D 2 O O 3 PO
+
N
+
N
H
N
H
H
Figure 9.5 Mechanism for PLP-dependent a-amino acid decarboxylases.
R
H D
NH 3
+