| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 263, Issue 25, 12204-12212, Sep, 1988
RE Cappel and HF Gilbert
In glutathione redox buffers, rat liver, microsomal 3-hydroxy-3-
methylglutaryl coenzyme A (HMG-CoA) reductase rapidly equilibrates between
a reduced, active form and an oxidized, inactive form. At pH 7.0, 37
degrees C, the second order rate constant for inactivation of the reduced
enzyme by GSSG is 1700 +/- 200 M-1 min-1, approximately 20- fold faster
than the reaction of GSSG with a typical, unhindered thiol of pKa 7.7. High
concentrations of GSH or lower concentrations of dithiothreitol restore the
activity of the oxidized enzyme. The oxidation of the enzyme by GSSG is
only 30-fold slower in the presence of saturating levels of both
substrates. The incomplete inhibition of thiol/disulfide exchange by
substrates can lead to significant changes in the activity of the enzyme
during the assay when glutathione is present. At redox equilibrium, both in
the absence and presence of substrates, the activity of the enzyme depends
on the quantity [GSH]2/[GSSG], suggesting that the redox transition
involves the formation of a protein-SS-protein disulfide. The equilibrium
constant for the reaction HMGRred + GSSG in equilibrium HMGRox + 2 GSH is
0.55 +/- 0.07 M in the absence of substrates and 0.20 +/- 0.02 M in the
presence of saturating levels of both substrates. Thus, HMG-CoA reductase
is very sensitive to dithiol oxidation both kinetically and
thermodynamically. Significant changes in the oxidation state and activity
of this enzyme could be expected to result from normal changes in the
thiol/disulfide oxidation state of the cellular glutathione redox buffer.
Thiol/disulfide exchange between 3-hydroxy-3-methylglutaryl-CoA reductase and glutathione. A thermodynamically facile dithiol oxidation
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Oda Functions of Sulfur-Containing Amino Acids in Lipid Metabolism J. Nutr., June 1, 2006; 136(6): 1666S - 1669S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Sanchez-Perez, M. Gasset, J. J. Calvete, and M. A. Pajares Role of an Intrasubunit Disulfide in the Association State of the Cytosolic Homo-oligomer Methionine Adenosyltransferase J. Biol. Chem., February 21, 2003; 278(9): 7285 - 7293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu and Y.-Y. Yeh S-Alk(en)yl Cysteines of Garlic Inhibit Cholesterol Synthesis by Deactivating HMG-CoA Reductase in Cultured Rat Hepatocytes J. Nutr., June 1, 2002; 132(6): 1129 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Pregel and A. C. Storer Active Site Titration of the Tyrosine Phosphatases SHP-1 and PTP1B Using Aromatic Disulfides. REACTION WITH THE ESSENTIAL CYSTEINE RESIDUE IN THE ACTIVE SITE J. Biol. Chem., September 19, 1997; 272(38): 23552 - 23558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Schalinske and R. S. Eisenstein Phosphorylation and Activation of both Iron Regulatory Proteins 1 and 2 in HL-60 Cells J. Biol. Chem., March 22, 1996; 271(12): 7168 - 7176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Arnone, M. Zannini, and R. D. Lauro The DNA Binding Activity and the Dimerization Ability of the Thyroid Transcription Factor I Are Redox Regulated J. Biol. Chem., May 19, 1995; 270(20): 12048 - 12055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hentze, T. Rouault, J. Harford, and R. Klausner Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction Science, April 21, 1989; 244(4902): 357 - 359. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
