Interaction between peroxidase and cyclooxygenase activities in prostaglandin-endoperoxide synthase. Interpretation of reaction kinetics.

作者: R.J. Kulmacz , R.B. Pendleton , W.E. Lands

DOI: 10.1016/S0021-9258(17)37493-8

关键词:

摘要: Prostaglandin-endoperoxide synthases have two distinct enzymatic activities in the biosynthesis of prostanoids: a peroxidase and fatty acid oxygenase. Hydroperoxides, such as cyclooxygenase reaction product, prostaglandin G2, act both substrates for synthase obligatory initiators itself. A mechanistic scheme was devised to describe interactions between synthase. This mechanism based on heme-dependent that observed with horseradish initiation by intramolecular intermediate. Rate equations derived from were numerically integrated an interactive computer program consolidated diverse phenomena provide quantitative predictions kinetics The agreed well experimental observations purified ovine seminal vesicle enzyme under wide variety conditions, including inhibition exogenous hydroperoxide scavenger cyanide, stimulation hydroperoxide, eicosapentaenoic oxygenation conditions where arachidonic reacts rapidly. detailed analyses made possible simulation important insights into catalytic control biosynthesis.

参考文章(40)
Richard J. Kulmacz, James F. Miller, Robert B. Pendleton, William E.M. Lands, [44] Cyclooxygenase initiation assay for hydroperoxides Methods in Enzymology. ,vol. 186, pp. 431- 438 ,(1990) , 10.1016/0076-6879(90)86136-J
D.A. Kujubu, B.S. Fletcher, B.C. Varnum, R.W. Lim, H.R. Herschman, TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue Journal of Biological Chemistry. ,vol. 266, pp. 12866- 12872 ,(1991) , 10.1016/S0021-9258(18)98774-0
J.A. DeGray, G Lassmann, J.F. Curtis, T.A. Kennedy, L.J. Marnett, T.E. Eling, R.P. Mason, Spectral analysis of the protein-derived tyrosyl radicals from prostaglandin H synthase. Journal of Biological Chemistry. ,vol. 267, pp. 23583- 23588 ,(1992) , 10.1016/S0021-9258(18)35878-2
D W Potter, J A Hinson, The 1- and 2-electron oxidation of acetaminophen catalyzed by prostaglandin H synthase. Journal of Biological Chemistry. ,vol. 262, pp. 974- 980 ,(1987) , 10.1016/S0021-9258(19)75736-6
G. Lassmann, R. Odenwaller, J.F. Curtis, J.A. DeGray, R.P. Mason, L.J. Marnett, T.E. Eling, Electron spin resonance investigation of tyrosyl radicals of prostaglandin H synthase. Relation to enzyme catalysis. Journal of Biological Chemistry. ,vol. 266, pp. 20045- 20055 ,(1991) , 10.1016/S0021-9258(18)54889-4
T.E. Eling, W.C. Glasgow, J.F. Curtis, W.C. Hubbard, J.A. Handler, Studies on the reduction of endogenously generated prostaglandin G2 by prostaglandin H synthase. Journal of Biological Chemistry. ,vol. 266, pp. 12348- 12355 ,(1991) , 10.1016/S0021-9258(18)98903-9
S. Ohki, N. Ogino, S. Yamamoto, O. Hayaishi, Prostaglandin hydroperoxidase, an integral part of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. Journal of Biological Chemistry. ,vol. 254, pp. 829- 836 ,(1979) , 10.1016/S0021-9258(17)37880-8
A M Lambeir, C M Markey, H B Dunford, L J Marnett, Spectral properties of the higher oxidation states of prostaglandin H synthase. Journal of Biological Chemistry. ,vol. 260, pp. 14894- 14896 ,(1985) , 10.1016/S0021-9258(18)95676-0
R J Kulmacz, A L Tsai, G Palmer, Heme spin states and peroxide-induced radical species in prostaglandin H synthase. Journal of Biological Chemistry. ,vol. 262, pp. 10524- 10531 ,(1987) , 10.1016/S0021-9258(18)60993-7