Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity.
Delta-6 desaturase, also known as fatty acid desaturase-2 (FADS2), is a component of a lipid metabolic pathway that converts the essential fatty acids linoleate and alpha-linolenate into long-chain polyunsaturated fatty acids. Isolation of Delta-6 desaturase/FADS2 cDNA from human skin predicts an identical protein to that expressed in human brain and Southern analysis indicates a single locus, together suggestive of a single Delta-6 desaturase/FADS2 gene. Within human skin, Delta-6 desaturase/FADS2 mRNA and protein expression is restricted to differentiating sebocytes located in the suprabasal layers of the sebaceous gland. Enzymatic analysis using CHO cells overexpressing human Delta-6 desaturase/FADS2 indicates catalysis of a "polyunsaturated fatty acid type" reaction, but also an unexpected "sebaceous-type" reaction, that of converting palmitate into the mono-unsaturated fatty acid sapienate, a 16-carbon fatty acid with a single cis double bond at the sixth carbon from the carboxyl end. Sapienate is the most abundant fatty acid in human sebum, and among hair-bearing animals is restricted to humans. This work identifies Delta-6 desaturase/FADS2 as the major fatty acid desaturase in human sebaceous glands and suggests that the environment of the sebaceous gland permits catalysis of the sebaceous-type reaction and restricts catalysis of the polyunsaturated fatty acid type reaction.
Ge
Lan
L
The Skin Research Center of Johnson and Johnson, CPWW., Skillman, New Jersey, USA.
Gordon
Joel S
JS
Hsuan
Charleen
C
Stenn
Kurt
K
Prouty
Stephen M
SM
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D050602:Linoleoyl-CoA Desaturase; D050356:Lipid Metabolism; D008956:Models, Chemical; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012627:Sebaceous Glands / Q000201:enzymology*; D012629:Sebum / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution
D018076:DNA, Complementary; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase