Biosynthesis and elongation of short- and medium-chain-length fatty acids.
Short- and medium-chain-length fatty acids (FAs) are important constituents of a wide array of natural products. Branched and straight short-chain-length FAs originate from branched chain amino acid metabolism, and serve as primers for elongation in FA synthase-like reactions. However, a recent model proposes that the one-carbon extension reactions that utilize 2-oxo-3-methylbutyric acid in leucine biosynthesis also catalyze a repetitive one-carbon elongation of short-chain primers to medium-chain-length FAs. The existence of such a mechanism would require a novel form of regulation to control carbon flux between amino acid and FA biosynthesis. A critical re-analysis of the data used to support this pathway fails to support the hypothesis for FA elongation by one-carbon extension cycles of alpha-ketoacids. Therefore, we tested the hypothesis experimentally using criteria that distinguish between one- and two-carbon elongation mechanisms: (a) isotopomer patterns in terminal carbon atom pairs of branched and straight FAs resulting from differential labeling with [(13)C]ăcetate; (b)(13)C]threonine labeling patterns in odd- and even chain length FAs; and (c) differential sensitivity of elongation reactions to inhibition by cerulenin. All three criteria indicated that biosynthesis of medium-chain length FAs is mediated primarily by FA synthase-like reactions.
van der Hoeven
R S
RS
Department of Plant Breeding and Biometry, 252 Emerson Hall, Cornell University, Ithaca, New York 14853, USA.
Steffens
J C
JC
D002247:Carbon Isotopes; D002569:Cerulenin / Q000737:chemistry / Q000494:pharmacology; D005227:Fatty Acids / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D019657:Solanaceae / Q000378:metabolism
D002247:Carbon Isotopes; D005227:Fatty Acids; D002569:Cerulenin