Mechanism of chain length determination in biosynthesis of milk fatty acids.
Fatty acid synthetases isolated from all mammalian tissues synthesize predominately palmitic acid. However, in vivo the mammary gland fatty acid synthetases of some species are responsible for the synthesis of medium chain fatty acids. The objective of this presentation is to outline the mechanism which regulates the product specificity of fatty acid synthetases in general and to illustrate how this control is modified in the mammary gland. Fatty acid synthetases isolated from mammalian tissues are composed of two similar, probably identical, polypeptides, each carrying as many as seven enzyme components. Thioesterase I, the component which functions to terminate growth of acyl chains on the multienzyme, is located at one terminus of each polyfunctional polypeptide and can be detached by limited proteolysis with trypsin. By studying separately the kinetics of chain elongation by the core of the trypsinized complex and of chain termination by the isolated thioesterase I component, it has been possible to establish that the specificities of the elongation and termination reactions account for the synthesis of predominantly the carbon-16 fatty acid by purified fatty acid synthetases. Mammary glands of some species contain an additonal enzyme, thioesterase II, which can modify the product specificity of fatty acid synthetase by hydrolyzing medium chain acyl moieties from thioester linkage to the 4'phosphopantetheine of the multienzyme. At all stages of development of rat mammary gland, the amount of theoesterase II present correlates well with the proportion of medium chain fatty acids synthesized by the gland. This mammary gland-specific thioesterase appears responsible for the ability of this tissue to synthesize medium chain fatty acids characteristic of milk fat.
D000818:Animals; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D006041:Goats; D006168:Guinea Pigs; D006868:Hydrolysis; D007700:Kinetics; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D008892:Milk / Q000201:enzymology*; D010084:Oxidation-Reduction; D010169:Palmitic Acids / Q000096:biosynthesis; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013869:Thiolester Hydrolases / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism
D005227:Fatty Acids; D010169:Palmitic Acids; D064429:Fatty Acid Synthases; D013869:Thiolester Hydrolases; C022738:thioesterase II; D010170:Palmitoyl-CoA Hydrolase; D014357:Trypsin