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

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.

Authors+Show Affiliations

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California 91010.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8239661

Citation

Esworthy, R S., et al. "Reactivity of Plasma Glutathione Peroxidase With Hydroperoxide Substrates and Glutathione." Archives of Biochemistry and Biophysics, vol. 307, no. 1, 1993, pp. 29-34.
Esworthy RS, Chu FF, Geiger P, et al. Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. Arch Biochem Biophys. 1993;307(1):29-34.
Esworthy, R. S., Chu, F. F., Geiger, P., Girotti, A. W., & Doroshow, J. H. (1993). Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. Archives of Biochemistry and Biophysics, 307(1), pp. 29-34.
Esworthy RS, et al. Reactivity of Plasma Glutathione Peroxidase With Hydroperoxide Substrates and Glutathione. Arch Biochem Biophys. 1993 Nov 15;307(1):29-34. PubMed PMID: 8239661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. AU - Esworthy,R S, AU - Chu,F F, AU - Geiger,P, AU - Girotti,A W, AU - Doroshow,J H, PY - 1993/11/15/pubmed PY - 1993/11/15/medline PY - 1993/11/15/entrez SP - 29 EP - 34 JF - Archives of biochemistry and biophysics JO - Arch. Biochem. Biophys. VL - 307 IS - 1 N2 - 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. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/8239661/Reactivity_of_plasma_glutathione_peroxidase_with_hydroperoxide_substrates_and_glutathione_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(83)71555-9 DB - PRIME DP - Unbound Medicine ER -