Plausible Mechanism for Inhibition of Succinyl-CoA Ligase Activity in Response to Vitamin B12 Depletion

This article [Brass et al., 1990: (http://jn.nutrition.org/cgi/reprint/120/3/290) (http://www.ncbi.nlm.nih.gov/pubmed/2319347?dopt=Abstract)] shows that inhibition of methylmalonyl-CoA mutase (MMM) activity by the administration of hydroxycobalamin[c-lactam], an analogue of 5'-deoxyadenosylcobalamin that inhibits MMM activity, increases propionyl-CoA levels in the livers of rats. This, in concert with other metabolic insults or inhibition of the TCA cycle by whatever causes, could conceivably produce the propionyl-CoA-mediated inhibition of succinyl-CoA ligase (a.k.a. succinate:CoA ligase) that Stumpf et al. (1980) [Stumpf et al., 1980: (http://www.ncbi.nlm.nih.gov/pubmed/6780967)] and others [Wajner and Coelho, 1997: (http://www.ncbi.nlm.nih.gov/pubmed/9427143)] have suggested as one of several mechanisms underlying mitochondrial dysfunction in methylmalonic aciduria. That effect, along with other factors, could produce mtDNA depletion.