Quantitative assessment of anaplerosis from propionate in pig heart in vivo.
Normal cardiac metabolism requires continuous replenishment (anaplerosis) of catalytic intermediates of the citric acid cycle. Little is known about the quantitative aspects of propionate as a substrate of in vivo anaplerosis; therefore, we measured the rate of propionate entry into the citric acid cycle in hearts of anesthetized pigs. [U-(13)C(3)]propionate (0.25 mM) was infused in a coronary artery branch for 1 h via an extracorporeal perfusion circuit, and cardiac biopsies were analyzed for the mass isotopomer distribution of citric acid cycle intermediates. Infusion of propionate did not affect myocardial oxygen consumption, heart rate, or contractile function. In the infused territory, propionate infusion did not affect uptake of glucose and lactate but decreased free fatty acid uptake by one-half (P < 0.05). Propionate extraction and uptake were 57.4 +/- 3.3% and 0.078 +/- 0.009 micromol x min(-1) x g(-1). Anaplerosis from propionate, calculated from the mass isotopomer distribution of succinate, accounted for 8.9 +/- 1.3% of the citric acid cycle flux. Propioylcarnitine release accounted for only 0.033 +/- 0.002% of propionate uptake. Methylcitrate did not accumulate. Thus administration of a low concentration of propionate appears to be a convenient and safe way to boost anaplerosis in the heart.
Martini
Wenjun Z
WZ
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-7139, USA.
Stanley
William C
WC
Huang
Hazel
H
Rosiers
Christine Des
CD
Hoppel
Charles L
CL
Brunengraber
Henri
H
D000818:Animals; D002247:Carbon Isotopes; D002952:Citric Acid Cycle / Q000502:physiology*; D013058:Mass Spectrometry; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D011422:Propionates / Q000493:pharmacokinetics*; D013552:Swine; D017725:Ventricular Pressure / Q000502:physiology
D002247:Carbon Isotopes; D011422:Propionates