Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 279, Issue 2, Pages 324-329Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/bbrc.2000.3930
Keywords
-
Categories
Funding
- NIA NIH HHS [R01 AG09235] Funding Source: Medline
- NIEHS NIH HHS [P30 ES06096] Funding Source: Medline
Ask authors/readers for more resources
The biosynthesis of reduced glutathione (GSH) is carried out by the enzymes gamma -glutamylcysteine synthetase (GCL) and GSH synthetase. GCL is the rate-limiting step and represents a heterodimeric enzyme comprised of a catalytic subunit (GCLC) and a (regulatory), or modifier, subunit (GCLM). The nonhomologous Gclc and Gclm genes are located on mouse chromosomes 9 and 3, respectively. GCLC owns the catalytic activity, whereas GCLM enhances the enzyme activity by lowering the K-m for glutamate and increasing the K-i to GSH inhibition. Humans have been identified with one or two defective GCLC alleles and show low GSH levels. As an initial first step toward understanding the role of GSH in cellular redox homeostasis, me have targeted a disruption of the mouse Gclc gene. The Gclc(-/-) homozygous knockout animal dies before gestational day 13, whereas the Gclc(+/-) heterozygote is viable and fertile. The Gclc(+/-) mouse exhibits a gene-dose decrease in the GCLC protein and GCL activity, but only about a 20% diminution in GSH levels and a compensatory increase of approximately 30% in ascorbate-as compared with that in Gclc(+/+) wild-type littermates These data show a reciprocal action between falling GSH concentrations and rising ascorbate levels. Therefore, the Gclc(+/-) mouse mag be a useful genetic model for mild endogenous oxidative stress. (C) 2000 Academic Press.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available