Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 3.7 GST nomenclature and tissue expression (Mannervik et al., 2005).Enzymesubunit

Class

Trivialnames

Tissue expression

Comments

GSTA1

Alpha

B1B1, GST2-

type 1,

e

Liver, intestine testis

o

kidney,

adrenal

>

pancreas

lung,

brain

>

heart

Inducible by oltipraz, sulforophane, and phenobarbital.GSTalpha comprises about 5% of liver

cytosolic proteins.

(^5) D
steroid isomerase
GSTA2
Alpha
B2B2, GST2-
type2,
g
Liver, pancreas, testis

kidney

adrenal

brain, lung, heart
Only 11 a.a. changes compared to GSTA1
GSTA3
Alpha
Lung, stomach, trachea, placenta
(^5) D
steroid isomerase
GSTA4
Alpha
All tissues, small intestine

spleen
GSTM1a
Mu
GST1-type 2,
m
Liver

testis

brain, adrenal, kidney,
pancreas

lung, heart
Polymorphic

about 40–60% of Caucasians
have a gene deletion (M1
0/
0).
GSTM1b
Mu
GST1-type 1,
Liver

testis

brain, adrenal, kidney,
pancreas

lung, heart
Allelic variation at codon 173 between (M1
A, M1
B)
GSTM2
Mu
GST4
Brain

testis

heart

pancreas

kidney

adrenal

lung, liver
84% identity with GSTM1-1 No polymorphisms identified
GSTM3
Mu
GST5
Testis
o
brain, lung Spleen

others
Polymorphism resulting in 3 bp deletion in
intron 6 that generate a YY1 response element
GSTM4
Mu
Liver, skeletal muscle

heart,brain

pancreas
GSTM5
Mu
Brain, testis, lung
GSTO1
Omega
Liver, heart, skeletal muscle, kidney
Monoethylarsonic acid, dehydroascorbic acid;
modulates Ca
2+
release by ryanodine receptors in
ER. Polymorphisms
"the risk of stroke and vascular
dementia. 20% homology to other GSTs
GSTO2
Omega
Testis
64% identity with GSTO1 Dehydroascorbic acid reductase
GSTP1
Pi
GST3,
p
Brain

lung, heart Testis

adrenal,
kidney, pancreas

liver
Large variations in expression. Highly
expressed in tumors Four variants
GSTS1
Sigma
S1-1
macrophages
Converts PGH
to PGD 2
2
GSTT1
Theta
f
Kidney, liver

small intestine

brain, spleen, testis, pancreas,
prostate
Null allele is 30–40% in Germans Partial
gene deletion in 15–25% other Caucasians.60% in Asians
GSTT2
Theta
Liver?
Truncation in C-terminal region: possibly a pseudogene
GSTZ1
Zeta
+four allelic
variants
liver
Activates dichloroacetic acid. Functions as maleylacetoacetate
isomerase. (tyrosine degradation)
74