HYPOTHESIS FOR THE INTERACTION OF HEME AND ARACHIDONIC-ACID IN THE SYNTHESIS OF PROSTAGLANDINS

被引：13

作者：

PETERSON, DA ^{[1
]}

GERRARD, JM ^{[1
]}

机构：

[1] UNIV MINNESOTA,HLTH SCI CTR,DEPT PEDIAT,MINNEAPOLIS,MN 55455

来源：

MEDICAL HYPOTHESES | 1979年 / 5卷 / 06期

关键词：

Arachidonic Acid; Fatty Acids; Heme; Hydroxylase; Iron; Oxygenase; Prostaglandins;

D O I：

10.1016/0306-9877(79)90089-6

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

A model is proposed for the interaction of arachidonic acid with the heme associated with the cyclo-oxygenase enzyme which synthesizes prostaglandin endoperoxides. According to this concept, arachidonic acid attaches with its carboxylic acid residue to one ligand of the Fe++ in heme, then curls around the outside of the protoporphyrin to react with a molecule of oxygen associated with the ligand of the Fe++ on the other side of the protoporphyrin with addition of O2 at the C11 carbon, ring closure across C8-12, formation of the C9-11 endoperoxide and then addition of a second oxygen at C15 with an allylic shift of the double bond. This concept may resolve several experimental findings relating to the mechanism of prostaglandin synthesis and can account for much of the stereospecificity in the conversion of arachidonic acid to prostaglandin G2. © 1979.

引用

页码：683 / 693

页数：11

共 30 条

[1]

BRESLOW R, 1965, ORGANIC REACTION MEC, P135

[2]

BUNN HF, 1968, J BIOL CHEM, V243, P465

[3] NATURE OF O-2 AND CO BINDING TO METALLOPORPHYRINS AND HEME PROTEINS [J].

COLLMAN, JP ;

BRAUMAN, JI ;

HALBERT, TR ;

SUSLICK, KS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (10) :3333-3337

[4] MODEL FOR PROSTAGLANDIN SYNTHETASE CYCLO-OXYGENATION SITE AND ITS INHIBITION BY ANTIINFLAMMATORY ARYLACETIC ACIDS [J].

GUND, P ;

SHEN, TY .

JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (09) :1146-1152

[5]

HAMBERG M, 1967, J BIOL CHEM, V242, P5329

[6]

HAMBERG M, 1967, J BIOL CHEM, V242, P5336

[7]

HAMBERG M, 1967, J BIOL CHEM, V242, P5344

[8] PROSTAGLANDIN ENDOPEROXIDES - NOVEL TRANSFORMATIONS OF ARACHIDONIC-ACID IN HUMAN PLATELETS [J].

HAMBERG, M ;

SAMUELSS.B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1974, 71 (09) :3400-3404

[9]

HEMLER M, 1976, J BIOL CHEM, V251, P5575

[10] PARTIAL DETERMINATION BY X-RAY METHODS, AND ITS CORRELATION WITH CHEMICAL DATA [J].

KENDREW, JC ;

PHILLIPS, DC ;

SHORE, VC ;

STRANDBERG, BE ;

WATSON, HC ;

DICKERSON, REF .

NATURE, 1961, 190 (477) :666-&

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