Metabolism of essential fatty acids by human epidermal enzyme preparations: evidence of chain elongation.
The present studies were undertaken in order to delineate the source of human epidermal arachidonic acid, 20:4(n-6). Epidermal microsomal preparations from normal (N) and diseased epidermis (clinically uninvolved (PU) and involved psoriatic (PI) epidermis) were incubated in vitro with either [14C]18:2(n-6), [14C]20:3(n-6) or [14C]malonyl CoA to determine the activities of the delta 6, delta 5 desaturases and elongate, respectively. Experiments were performed in parallel with rat liver microsomal preparations where enzyme activities are well documented. Data derived from the enzymatic assays were compared to fatty acid composition data derived from epidermal total lipids. The enzymatic conversion rates were determined after methylation and separation of the 14C-labeled fatty acid methyl esters by argentation thin-layer chromatography and reverse phase high-performance liquid chromatography. Our data demonstrated: that N, PU, and PI epidermis were all capable of elongating 18:3(n-6) into 14C-labeled 20:3(n-6) via the addition of [14C]malonyl CoA, and this activity was markedly elevated (fivefold) in PI preparations; that N, PU, and PI epidermal preparations lacked the capacity to desaturate 18:2(n-6) and 20:3(n-6); and striking alterations in the individual fatty acids (as weight percent) in the total fatty acids of the PI epidermal extracts when compared to the PU and N extracts. These findings indicate that epidermal arachidonic acid is not biosynthesized locally from tissue linoleic acid and must, therefore, depend on contribution from another endogenous source.
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D000090943:Delta-5 Fatty Acid Desaturase; D004817:Epidermis / Q000201:enzymology*; D044943:Fatty Acid Desaturases / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005228:Fatty Acids, Essential / Q000378:metabolism*; D006801:Humans; D050602:Linoleoyl-CoA Desaturase; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D010441:Peptide Chain Elongation, Translational; D011565:Psoriasis / Q000201:enzymology; D051381:Rats; D012867:Skin / Q000201:enzymology
D001095:Arachidonic Acids; D000090943:Delta-5 Fatty Acid Desaturase; D005228:Fatty Acids, Essential; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases