Mechanism of fatty acid desaturation: a bioorganic perspective.
The desaturation of long chain fatty acids is a ubiquitous transformation which plays a critical role in the biosynthesis of lipids. Of particular interest to the bioorganic chemist is the unique ability of desaturases to oxidize unactivated hydrocarbon chains in a chemo-, regio- and stereoselective manner. The mechanism of membrane-bound desaturases has been examined using regiospecifically labelled analogues bearing deuterium, sulfur or fluorine-substituted methylene isosteres. These probes have been applied in the study of several biomedically important desaturase systems including a prototypical yeast stearoyl CoA delta(9) desaturase. In all cases, it has been found that the dehydrogenation (desaturation) process is initiated by a kinetically important hydrogen activation step at the carbon of the incipient double bond which is closest to the acyl terminus of the fatty acid chain. These results point to a common active site architecture which is highly conserved among a wide range of membranous desaturases.
Behrouzian
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Department of Chemistry, Carleton University, Ottawa-Carleton Chemistry Institute, 1125 Colonel By Drive, Ottawa, Ont., Canada K1S 5B6.
Buist
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D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002708:Chlorella / Q000201:enzymology; D044943:Fatty Acid Desaturases / Q000737:chemistry* / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D006859:Hydrogen; D050356:Lipid Metabolism; D008956:Models, Chemical; D010944:Plants / Q000201:enzymology; D017434:Protein Structure, Tertiary
D005227:Fatty Acids; D006859:Hydrogen; D044943:Fatty Acid Desaturases