Propionate metabolism in the rat heart by ¹³C n.m.r. spectroscopy

High-resolution ¹³C n.m.r. spectroscopy has been used to examine propionate metabolism in the perfused rat heart. A number of tricarboxylic acid (TCA) cycle intermediates are observable by ¹³C n.m.r. in hearts perfused with mixtures of pyruvate and propionate. When the enriched ¹³C-labelled nucleus originates with pyruvate, the resonances of the intermediates appear as multiplets due to formation of multiply-enriched ¹³C-labelled isotopomers, whereas when the ¹³C-labelled nucleus originates with propionate, these same intermediates appear as singlets in the ¹³C spectrum since entry of propionate into the TCA cycle occurs via succinyl-CoA. An analysis of the isotopomer populations in hearts perfused with [3-¹³C]pyruvate plus unlabelled propionate indicates that about 27% of the total pyruvate pool available to the heart is derived directly from unlabelled propionate. This was substantiated by perfusing a heart for 2 h with [3-¹³C]-propionate as the only available exogenous substrate. Under these conditions, all of the propionate consumed by the heart, as measured by conventional chemical analysis, ultimately entered the oxidative pathway as [2-¹³C] or [3-¹³C]pyruvate. This is consistent with entry of propionate into the TCA cycle intermediate pools as succinyl-CoA and concomitant disposal of malate to pyruvate via the malic enzyme. ¹³C resonances arising from enriched methylmalonate and propionylcarnitine are also detected in hearts perfused with [3-¹³C] or [1-¹³C]propionate which suggests that ¹³C n.m.r. may be useful as a non-invasive probe in vivo of metabolic abnormalities involving the propionate pathway, such as methylmalonic aciduria or propionic acidaemia.