Methylmalonate, incorporation into

Kaneda, T., and J. W. Corcoran a-Methylmalonate incorporation into the branched chain lactone in erythromycin. Federation Proc. 20, 273 (1961). 

Vitamin deficiency can cause a megaloblastic anemia of the same type seen in folate deficiency (discussed in Chapter 17). In a patient with megaloblastic anemia, it is important to determine the underlying cause because Bjj defidency, if not corrected, produces a peripheral neuropathy owing to aberrant fatty acid incorporation into the myelin sheets associated with inadequate methylmalonyl CoA mutase activity. Excretion of methylmalonic acid indicates a vitamin Bjj deficiency rather than folate. 

Massart-Leen et al. (1981) analyzed bovine milk fat and goat milk fat for branched chain fatty acids. They did not find the same diversity of fatty acids in bovine as in goat milk fat and as previously reported. The authors suggested that the difference—the absence of branched chain acids other than iso and anteiso in bovine milk fat—could be caused by the relative inefficiency of the incorporations of methylmalonic acid into the biosynthetic pathway. 

DEBS 1+TE was also shown to efficiently incorporate an advanced chain elongation intermediate, (2S, 3i )-2-methyl-3-hydroxypentanoyl-N-acetylcysteamine (NAC) thioester, into the triketide lactone [159]. (2S,3J )-2-methyl-hydroxybuty-ryl-NAC is also turned over by DEBS 1+TE and converted into the Cg-lactone, normally derived from an acetate starter and methylmalonate extenders [ 161 ] (Fig. 9). Thus, it is evident that these NAC-thioesters are treated as diketide intermediates, not as starter substrates by the enzyme, suggesting that the substitution pattern and not the chain length is crucial for the recognition of substrates by DEBS. 

A photochemical route to racemic estrone commencing with 2-bromo-5-methoxytoluene depended upon the generation of a quinodimethane intermediate incorporating an enolic component (ref. 129). Subsequently the method was adapted to furnish an asymmetric synthesis of (+)-estrone as described in the ensuing section. The cyclopentanone component was derived by the reaction of dimethyl malonate with E-1,4-dibromobut-2-ene to give racemic dimethyl 2-vinylcyclopropane-1,1-dicarboxylate which was then transformed by reaction with dimetyl methylmalonate followed by hydrolysis into racerruc 2-methyl-3-vinylcyclopentanone. 

In vertebrates, in addition to the main pathway of propionate catabolism (conversion into succinate), alternative pathways may function under conditions when the main pathway is blocked. In the termite Zootermopsis angusticollis a high Bn content apparently is due to the presence of microorganisms in the stomach (Wakayama et al., 1984). There is evidence that vitamin Bn is used by termites for the conversion of succinate to methylmalonate and incorporation of the latter instead of malonyl-CoA into methyl-branched hydrocarbons. Therefore, in termites the direction of carbon flow is the same as in bacteria (from succinate to propionate), but opposite to that found in vertebrates. From the aforesaid it is clear that studying propionic acid fermentation is important not only for understanding the biochemistry of propionic acid bacteria, but of many other organisms, including humans. 

---