Succinate from valine

The methylmalonyl-CoA unit, which is the precursor to methyl-branched fatty acids and hydrocarbons, arises from the carbon skeletons of valine and isoleucine, but not succinate (Dillwith et al., 1982). Propionate is also a precursor to methylmalonyl-CoA, and in the course of these studies, a novel pathway for... 

Some insects use hydrocarbons as sex pheromones. For example, the housefly, Musca domestica, uses a mixture including (Z) -9-tricosene, the corresponding epoxide and ketone, and several methyl alkanes (2iI). The tricosene is derived by chain elongation of oleic acid, and the epoxide and ketone are made from it. The methyl alkanes are made de novo from acetate and propionate, with one propionate unit per molecule supplying the branch carbon. Propionate can arise from the degradation of valine or isoleucine, but not from succinate, although succinate may serve as an acetate precursor. 

Insects utilize propionate and methylmalonate in the biosynthesis of ethyl branched juvenile hormones and methyl branched cuticular hydrocarbons. The sources of propionate and methylmalonate in some insects appear to differ from those in mammals. Succinate is the precursor of propionate and methylmalonate in a termite, whereas valine and probably other amino acids are the sources of propionate and methylmalonate in several other species. An unusual pathway for propionate metabolism has been shown to occur in insects and it may be related to the absence or low levels of vitamin B found in many species. Propionate is converted directly to acetate with carbon 1 of propionate lost as C02> carbon 2 of propionate becoming the methyl carbon of acetate and carbon 3 of propionate becoming the carboxyl carbon of acetate. This pathway suggested the possibility that 2-fluoropropionate might be selectively metabolized in insects to the toxic 2-fluoro-acetate. However, preliminary data indicate that 2-fluoropropionate is not toxic to the housefly or the American cockroach. 

To explain the labeling of all 4 carbons in the acetoacetate formed from 2-methyl-C -butyrate (reactions 6, 7, and 8) it is proposed that randomization occurs by CO2 fixation to pyruvate to form oxalacetate, which is then converted to the symmetric succinate. The problem is the same as that discussed in connection with the oxidation of valine (see p. 64). 

Modifications of the breakdown are necessitated by methyl branching. Branched-chain fatty acids arise also from the amino acids leucine, isoleucine, and valine (cf. Chapt. XII-5). Propionyl-CoA (instead of acetyl-CoA), is formed from isoleucine and valine, and this is converted to succinate by carboxylation and isomerization. 

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