The metabolic transformations of columbinic acid and the effect of topical application of the major metabolites on rat skin.
The metabolism of columbinic acid by various fatty acid oxidizing enzyme systems was studied. A cyclooxygenase product, 9-hydroxy-(5E,10E,12Z)-octadecatrienoic acid, was formed nearly quantitatively by ram seminal vesicle microsomes and in small amounts by washed human platelets. The major lipoxygenase product from washed human platelets, soybean lipoxygenase, and neonatal rat epidermal homogenate was 13-hydroxy-(5E,9Z,11E)-octadecatrienoic acid, although lesser quantities of other isomers differing in the double bond configurations were also identified by ultraviolet spectrophotometry and gas chromatography-mass spectroscopy. Topical application of the major lipoxygenase product to paws of essential fatty acid-deficient rats resulted in nearly as complete resolution of the scaly dermatitis as did the application of columbinic acid itself; the cyclooxygenase product was not at all effective.
D015094:3-Hydroxyacyl CoA Dehydrogenases; D000102:Acetyl-CoA C-Acyltransferase; D000287:Administration, Topical; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D019748:Carbon-Carbon Double Bond Isomerases; D002851:Chromatography, High Pressure Liquid; D004746:Enoyl-CoA Hydratase; D005228:Fatty Acids, Essential / Q000172:deficiency; D006801:Humans; D008042:Linolenic Acids / Q000378:metabolism* / Q000627:therapeutic use; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D019998:Racemases and Epimerases; D051381:Rats; D012669:Seminal Vesicles / Q000378:metabolism; D012756:Sheep; D012867:Skin / Q000187:drug effects*; D012871:Skin Diseases / Q000188:drug therapy
D005228:Fatty Acids, Essential; D008042:Linolenic Acids; D009097:Multienzyme Complexes; C038784:fatty acid oxidation complex; C034302:5,9,12-octadecatrienoic acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; D019748:Carbon-Carbon Double Bond Isomerases