Glutathione S-transferases: A review

A E Salinas, Margaret G Wong

Research output: Contribution to journalReview articleResearchpeer-review

426 Citations (Scopus)

Abstract

The Glutathione S-transferases (GSTs) form a group of multi-gene isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds. GSTs have been divided into a number of subclasses, alpha, mu, pi, and theta. The classification was made on the basis of sequence similarity and immunological cross-reactivity. GSTs show a high level of specificity toward GSH but the electrophilic second substrate can vary significantly both between and within the classes in spite of their sequence similarity. X-ray crystallography and site-directed mutagenesis studies have together elucidated the structure and mechanism of GSTs. Catalysis occurs by conjugation with glutathione (GSH) and the less toxic and more hydrophilic products can then be partially metabolised and excreted. This invaluable service is however disadvantageous during chemotherapy where GSTs have been associated with multi-drug resistance of tumour cells. Levels of expression of different isoforms of GSTs are tissue specific. The variations in expression between normal and tumour cells are of interest and in most cases the levels of GSTs are increased, especially p-GST. Understanding the complex role that GSTs play in drug resistance begins with determining the pattern of isoform expression and the substrate specificities of each isoform. The use of isozyme-specific, GSH analogues as inhibitors to modulate GST activity during chemotherapy is a promising strategy in the battle against cancer. This review attempts to provide a detailed overview of the literature concerning the different classes of GSTs, their function and mechanism and the use of GSTs as therapeutic targets for disease as current at the time of submission.

Original languageEnglish
Pages (from-to)279-309
Number of pages31
JournalCurrent Medicinal Chemistry
Volume6
Issue number4
Publication statusPublished - Apr 1999
Externally publishedYes

Fingerprint

Glutathione Transferase
Protein Isoforms
Chemotherapy
Isoenzymes
Tumors
Cells
Drug Therapy
Neoplasms
Detoxification
Mutagenesis
Poisons
X ray crystallography
X Ray Crystallography
Multiple Drug Resistance
Xenobiotics
Substrates
Substrate Specificity
Site-Directed Mutagenesis
Catalysis
Drug Resistance

Cite this

Salinas, A E ; Wong, Margaret G. / Glutathione S-transferases : A review. In: Current Medicinal Chemistry. 1999 ; Vol. 6, No. 4. pp. 279-309.
@article{9d173572dd954d8fa94eb0a919892fa2,
title = "Glutathione S-transferases: A review",
abstract = "The Glutathione S-transferases (GSTs) form a group of multi-gene isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds. GSTs have been divided into a number of subclasses, alpha, mu, pi, and theta. The classification was made on the basis of sequence similarity and immunological cross-reactivity. GSTs show a high level of specificity toward GSH but the electrophilic second substrate can vary significantly both between and within the classes in spite of their sequence similarity. X-ray crystallography and site-directed mutagenesis studies have together elucidated the structure and mechanism of GSTs. Catalysis occurs by conjugation with glutathione (GSH) and the less toxic and more hydrophilic products can then be partially metabolised and excreted. This invaluable service is however disadvantageous during chemotherapy where GSTs have been associated with multi-drug resistance of tumour cells. Levels of expression of different isoforms of GSTs are tissue specific. The variations in expression between normal and tumour cells are of interest and in most cases the levels of GSTs are increased, especially p-GST. Understanding the complex role that GSTs play in drug resistance begins with determining the pattern of isoform expression and the substrate specificities of each isoform. The use of isozyme-specific, GSH analogues as inhibitors to modulate GST activity during chemotherapy is a promising strategy in the battle against cancer. This review attempts to provide a detailed overview of the literature concerning the different classes of GSTs, their function and mechanism and the use of GSTs as therapeutic targets for disease as current at the time of submission.",
author = "Salinas, {A E} and Wong, {Margaret G}",
year = "1999",
month = "4",
language = "English",
volume = "6",
pages = "279--309",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers",
number = "4",

}

Salinas, AE & Wong, MG 1999, 'Glutathione S-transferases: A review' Current Medicinal Chemistry, vol. 6, no. 4, pp. 279-309.

Glutathione S-transferases : A review. / Salinas, A E; Wong, Margaret G.

In: Current Medicinal Chemistry, Vol. 6, No. 4, 04.1999, p. 279-309.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Glutathione S-transferases

T2 - A review

AU - Salinas, A E

AU - Wong, Margaret G

PY - 1999/4

Y1 - 1999/4

N2 - The Glutathione S-transferases (GSTs) form a group of multi-gene isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds. GSTs have been divided into a number of subclasses, alpha, mu, pi, and theta. The classification was made on the basis of sequence similarity and immunological cross-reactivity. GSTs show a high level of specificity toward GSH but the electrophilic second substrate can vary significantly both between and within the classes in spite of their sequence similarity. X-ray crystallography and site-directed mutagenesis studies have together elucidated the structure and mechanism of GSTs. Catalysis occurs by conjugation with glutathione (GSH) and the less toxic and more hydrophilic products can then be partially metabolised and excreted. This invaluable service is however disadvantageous during chemotherapy where GSTs have been associated with multi-drug resistance of tumour cells. Levels of expression of different isoforms of GSTs are tissue specific. The variations in expression between normal and tumour cells are of interest and in most cases the levels of GSTs are increased, especially p-GST. Understanding the complex role that GSTs play in drug resistance begins with determining the pattern of isoform expression and the substrate specificities of each isoform. The use of isozyme-specific, GSH analogues as inhibitors to modulate GST activity during chemotherapy is a promising strategy in the battle against cancer. This review attempts to provide a detailed overview of the literature concerning the different classes of GSTs, their function and mechanism and the use of GSTs as therapeutic targets for disease as current at the time of submission.

AB - The Glutathione S-transferases (GSTs) form a group of multi-gene isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds. GSTs have been divided into a number of subclasses, alpha, mu, pi, and theta. The classification was made on the basis of sequence similarity and immunological cross-reactivity. GSTs show a high level of specificity toward GSH but the electrophilic second substrate can vary significantly both between and within the classes in spite of their sequence similarity. X-ray crystallography and site-directed mutagenesis studies have together elucidated the structure and mechanism of GSTs. Catalysis occurs by conjugation with glutathione (GSH) and the less toxic and more hydrophilic products can then be partially metabolised and excreted. This invaluable service is however disadvantageous during chemotherapy where GSTs have been associated with multi-drug resistance of tumour cells. Levels of expression of different isoforms of GSTs are tissue specific. The variations in expression between normal and tumour cells are of interest and in most cases the levels of GSTs are increased, especially p-GST. Understanding the complex role that GSTs play in drug resistance begins with determining the pattern of isoform expression and the substrate specificities of each isoform. The use of isozyme-specific, GSH analogues as inhibitors to modulate GST activity during chemotherapy is a promising strategy in the battle against cancer. This review attempts to provide a detailed overview of the literature concerning the different classes of GSTs, their function and mechanism and the use of GSTs as therapeutic targets for disease as current at the time of submission.

M3 - Review article

VL - 6

SP - 279

EP - 309

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 4

ER -