Odd-chain fatty acids are thosefatty acids that contain an odd number ofcarbon atoms. In addition to being classified according to theirsaturation orunsaturation, fatty acids are also classified according to their odd or even numbers of constituent carbon atoms. With respect to natural abundance, most fatty acids are even chain, e.g.palmitic (C16) andstearic (C18). In terms of physical properties, odd and even fatty acids are similar, generally being colorless, soluble in alcohols, and often somewhat oily.^[1] The odd-chain fatty acids are biosynthesized and metabolized slightly differently from the even-chained relatives. In addition to the usual C12-C22 long chain fatty acids, somevery long chain fatty acids (VLCFAs) are also known. Some of these VLCFAs are also of the odd-chain variety.^[2]

The most common OCFA are the saturated C15 and C17derivatives, respectivelypentadecylic acid andmargaric acid.^[3] Even-chainedfatty acids are synthesized by assemblingacetyl-CoA precursors. Because the segments are each two carbons in length the resulting fatty acid has an even number of carbon atoms in it. However,propionyl-CoA instead of acetyl-CoA is used as the primer for the biosynthesis oflong-chain fatty acids with an odd number of carbon atoms.^[4]

Compared to theoxidation of even-numbered fatty acids, the oxidation of odd-chain fatty acids produces propionyl-CoA in addition to acetyl-CoA, which means that the oxidation requires three additional enzymes. The first ispropionyl-CoA carboxylase. This enzyme is responsible forcarboxylating theα-carbon of a propionyl-CoA to produce D-methylmalonyl-CoA.^[5] After this,methylmalonyl-CoA epimerase carries out anisomerization reaction. Specifically, the D-isomer produced by the carboxylase reaction is transformed into the L-isomer of methylmalonyl-CoA. This is a recently discovered enzyme, it was researched during the late 1900s and the first publication was in 1961. Researchers concluded that there was indeed a racemic reaction prior to reachingsuccinyl-CoA.^[6] Finally,methylmalonyl-CoA mutase, avitamin B₁₂-dependent enzyme, converts L-methylmalonyl-CoA into succinyl-CoA using a free radical mechanism. Succinyl-CoA is an intermediate of theTCA cycle and can readily enter there.^[7]

OCFAs are found particularly inruminant fat andmilk (e.g. pentadecylic acid).Some plant-based fatty acids also have an odd number of carbon atoms and Phytanic fatty acid absorbed from the plantchlorophyll has multiplemethyl branch points. As a result, it breaks down into three odd-numbered 3C Propionyl segments as well as three even-numbered 2C Acetyl segments and one even numbered 4C Isobutynoyl segment. In humans, propionic acid is produced by intestinal bacteria in the gut.^[8] In humans, in sharp contrast tobutyrate andoctanoate, the odd-chainSCFA,propionate, has no inhibitory effect onglycolysis and does not stimulateketogenesis.^[9] Odd-chain and branched-chain fatty acids, which form propionyl-CoA, can serve as minor precursors forgluconeogenesis.^[10][4]