Faculty Collaboration Database

Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. Arch Biochem Biophys 1993 Nov 15;307(1):29-34

Date

11/15/1993

Pubmed ID

8239661

DOI

10.1006/abbi.1993.1555

Scopus ID

2-s2.0-0027436058 (requires institutional sign-in at Scopus site)   74 Citations

Abstract

We studied enzyme kinetics parameters of plasma glutathione peroxidase (GSHPx-P) and the major cellular enzyme, GSHPx-1, for the substrates, H2O2, linoleic acid hydroperoxide (LinOOH), and glutathione (GSH). The major objectives were to determine whether the relatively slow GSHPx-P enzyme had a lower reactivity with hydroperoxides or with GSH and to identify favored hydroperoxide substrates. The rate constants describing the reactivity of human GSHPx-P and human GSHPx-1 with LinOOH and H2O2 are in the same range; GSHPx-P is more reactive with LinOOH and GSHPx-1 is more reactive with H2O2. GSHPx-P also has a low level of reducing activity toward cholesterol 7 alpha-OOH and no detectable activity with the 5 alpha-OOH isomer in contrast to phospholipid hydroperoxide glutathione peroxidase (PHGPx) which readily reduced both isomers. GSHPx-P catalytic activity toward phospholipid hydroperoxides is demonstrable in the absence of detergents, enhanced at low concentrations by deoxycholate, and strongly inhibited by Triton X-100 and incorporation into liposomes. These properties are the opposite of PHGPx. These results suggest that GSHPx-P largely lacks the membrane interfacial properties of PHGPx. GSHPx-P exhibits a smaller GSH rate constant than GSHPx-1. This property partially explains the slower turnover of GSHPx-P with several hydroperoxide substrates; the low reactivity with GSH is not consistent with efficient GSHPx function in the bulk plasma volume. GSHPx-P kinetic properties suggest that it would function best as a free fatty acid hydroperoxidase in GSH-rich microenvironments. Minimally, the secretion of reduced enzyme would permit it to scavenge free fatty acid hydroperoxides.

Author List

Esworthy RS, Chu FF, Geiger P, Girotti AW, Doroshow JH

Author

Albert W. Girotti PhD Adjunct Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Glutathione Peroxidase
Humans
Hydrogen Peroxide
Isoenzymes
Kinetics
Linoleic Acids
Lipid Peroxides
Male
Rats
Rats, Sprague-Dawley
Substrate Specificity
Testis