GSTs (EC 2.5.1.18) are a group of dimeric detoxification enzymes
catalyzing the conjugation of reduced glutathione (GSH) with a broad
spectrum of electrophiles.
5 This is important for
detoxification of xenobiotics and endogenous toxic compounds and for
protection of tissues from oxidative damage. The members of the GST
family are placed into multigene classes of Alpha, Mu, Pi, Kappa,
Theta, and Zeta according to the basis of sequence
identity.
6 7 8 Among these classes of GSTs, genetic
polymorphism is described for the GSTM1, GSTM3, GSTT1, GSTP1, and GSTZ1
loci. There are three alleles at the GSTM1 locus:
GSTM1*0,
GSTM1*A, and
GSTM1*B.
GSTM1*0 is a deletion,
and homozygotes express neither mRNA nor protein. Alleles
GSTM1*A and
GSTM1*B encode monomers that form
homo- and heterodimeric enzymes: GSTM1a-1a, GSTM1b-1b, and
GSTM1a-1b.
6 As in GSTM1, the null allele is also described
for the GSTT1 locus, and homozygotes for the
GSTT1*0 allele
express no enzyme.
9 The human GSTM3 gene is polymorphic
with two alleles:
GSTM3*A and
GSTM3*B. GSTM3*B has a 3-bp deletion in intron 6, which creates a recognition motif for
the YY1 transcription factor.
10 Recently, polymorphism in
the glutathione
S-transferase GSTP1 gene has been
identified with six common phenotypes resulting from homo- and
heterodimeric combinations of
GSTP1*A, GSTP1*B, and
GSTP1*C.
11 The transitions changed codon 105
from ATC (Ile) in
GSTP1*A to GTC (Val) in
GSTP1*B and
GSTP1*C and also codon 114 from GCG (Ala) to GTG (Val)
in
GSTP1*C. Both amino acid changes are in the
electrophile-binding active site of the GST P1-1 enzyme, and GST P1-1
isoforms have shown to possess different enzymatic
activities.
12