Key result
Propionate infusion decreases endogenous propionyl-CoA production, with total anaplerosis plateauing at ~16% of CAC flux.
Exogenous propionate inhibits cardiac protein catabolism, suggesting a mechanism for the beneficial effects of triheptanoin therapy in long-chain fatty acid oxidation disorders.
Suggests propionate may suppress cardiac protein catabolism in animals; leaves open relevance to triheptanoin in fatty acid oxidation disorders.
We applied mass isotopomer analysis utilizing GC‐MS and IR‐MS to a study of anaplerosis in rat hearts perfused with various concentrations of [U‐ 13 C 3 ] and [3‐ 13 C]‐propionate (0.1 to 3.0 mM) for 30 min. Total anaplerosis from propionyl‐CoA (unlabeled endogenous and [U‐ 13 C 3 ]propionyl‐CoA), expressed as a fraction of citric acid flux, was calculated by the M3 labeling ratio (succinyl‐CoA)/0.97(propionyl‐CoA). Using the M3 enrichment of propionyl‐CoA, total anaplerosis from propionyl‐CoA can be divided into (i) anaplerosis from endogenous unlabeled propionyl‐CoA and (ii) anaplerosis from [U‐ 13 C 3 ]propionyl‐CoA. Total propionyl‐CoA anaplerosis plateaued at 1 mM propionate (16% of the CAC flux). The infusion of propionate decreased the production of propionyl‐CoA from endogenous amino acids in a concentration depending manner. This most likely reflects inhibition of catabolism by exogenous propionate in the heart. A similar decrease in heart protein catabolism may occur during dietary therapy of patients with long‐chain fatty acid oxidation disorders with triheptanoin (a propionyl‐CoA precursor). This may contribute to the beneficial effect of triheptanoin therapy on cardiac function. Supported by NIH Roadmap grant R33DK070291 and grant 0465221 from the American Heart Association.
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Kasumov et al. (2006) studied this question. Propionate was evaluated on Total anaplerosis from propionyl-CoA and production of propionyl-CoA from endogenous amino acids. Infusion of propionate decreased the production of propionyl-CoA from endogenous amino acids in a concentration-dependent manner, with total anaplerosis plateauing at 16% of CAC flux at 1 mM.
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