Methylmalonic acid methyl-branched fatty acids

In vertebrates, the major sources of propionate and methylmalonate are odd chain fatty acids and the amino acids isoleucine, valine and methionine (8,9). In the termite Zootermopsls angusticollls. which can incorporate propionate as the methyl branch unit of mono- and dimethylalkanes (7), these sources were considered unlikely because the diet of termites presumably contains little fatty acid and Z. angusticollls contains very small amounts of odd chain length fatty acids (Chu and Blomqulst, unpublished). Likewise, termites would be expected to conserve essential amino acids such as the ones that could serve as precursors to propionate and methylmalonate. 

GC-MS has been responsible for the identification of a variety of unusual lipids associated with diseased conditions. Hydroxyocta-decadienoic esters of cholesterol for example, have been isolated from aortal atheroma placques [277] and branched chain and odd numbered fatty acids identified in the glycerolipids of brain, spinal cord and sciatic nerve [278] from a patient with methylmalonic aciduria. The latter compounds are thought to arise by the replacement of malonyl CoA with methyl malonyl CoA, and acetyl CoA with propionyl CoA at certain stages of fatty acid synthesis. In these and other examples, the lipids need to be hydrolysed to permit the identification of the constituent fatty acids. As the class of lipids is usually known from the separation procedure used, the nature of the fatty acids may allow the characterisation of the complete molecule. However, volatilisation of the intact lipid into the mass spectrometer when possible would be preferable, particularly when it is present in a mixture and separation of the components is first made by GC. 

Methylmalonyl-CoA may participate in fatty acid biosynthesis in place of malonyl-CoA, with the formation of methyl-branched long-chain (C17) fatty acids, and these acids have been isolated from glycerolipids of brain, spinal cord and sciatic nerve of a patient with methylmalonic aciduria and homo-cystinuria (Kishimoto et al., 1973). Odd-carbon-number straight-chain fatty acids (Ci5 and C17), due presumably to the accumulation of propionyl-CoA and the utilization of this substrate in fatty acid biosynthesis (Section 11.1), have also been observed in the central nervous system tissues of this patient (Kishimoto et aL, 1973), and another (the fourth described. Section 11.2.3) also with combined methylmalonic aciduria and homocystinuria (Dayan and Ramsay, 1974). It is relevant that methylmalonic acid may be utilized for the... 

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