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.
Sherry
A D
AD
Department of Chemistry, University of Texas at Dallas, Richardson 75083-0688.
Malloy
C R
CR
Roby
R E
RE
Rajagopal
A
A
Jeffrey
F M
FM
D000818:Animals; D002247:Carbon Isotopes; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008764:Methylmalonic Acid / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011422:Propionates / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats
D002247:Carbon Isotopes; D011422:Propionates; D011773:Pyruvates; C003223:propionylcarnitine; D019289:Pyruvic Acid; D008764:Methylmalonic Acid; C029658:propionic acid; D002331:Carnitine