Chemistry Reference
In-Depth Information
2
Vitamin B6 Enzyme Models
Lei Liu and Ronald Breslow
2.1
Introduction
Pyridoxal 5
0
-phosphate (PLP) and pyridoxamine 5
0
-phosphate (PMP) (Figure 2.1) are
the active forms of vitamin B6 that function as cofactors for amino acid metabolizing
enzymes [1]. These enzymes catalyze various reactions: (i) transamination between an
a
-amino acid and an
a
-keto acid; (ii) racemization of a chiral
a
-amino acid; (iii) elim-
ination of an electronegative group at the
b
-or
c
-position of an
a
-amino acid to give the
corresponding
a
-keto acid and ammonia; (iv) replacement of an electronegative group
at the
b
-or
c
-position of an
a
-amino acid or keto acid with another substituent; (v)
decarboxylation of an
-amino acid to give an amine; (vi) aldolase-type reaction accom-
panied with a C-C bond cleavage at the
a
-amino acid.
In vitamin B6-dependent enzymes, PLP is invariably bound to an active site lysine
through a Schiff base linkage, the internal aldimine. Its 5
0
-phosphate group is firmly
attached to the protein matrix through up to nine hydrogen bonds, and often by charge
interactions [2]. An external aldimine Schiff base, derived by transimination of the
internal aldimine with a substrate amino acid, is a common intermediate for all vi-
tamin B6-dependent enzymatic reactions. Due to the electron-sink effect of the con-
jugated pyridine segment, one of the three bonds around the
a
,
b
-position of a
b
-hydroxy-
a
-carbon atom of the
amino acid moiety in the intermediate undergoes cleavage (Scheme 2.1) [3]. Through
a
Figure 2.1 Pyridoxal 5
0
-phosphate and pyridoxamine 5
0
phosphate.
*
Note: This chapter reviews both the work done in
the Breslow laboratory and that done elsewhere.
When “we“ is used in the chapter it refers to work
in the Breslow laboratory generally, not just that
performed by Lei Liu. The full list of the authors
involved in each case appears in the references.
