Pyruvate and lactate metabolism in the in vivo dog heart.
Pyruvate increases the phosphorylation potential in perfused heart to a greater extent than the closely correlated substrate L-lactate. Therefore, metabolism of these compounds was studied in the myocardium of intact dogs. Phosphocreatine/ATP was increased 23% at 5.3 mM plasma pyruvate but was not significantly increased by lactate except at the highest concentration (17.5 mM in blood). Calculated [ADP] fell during pyruvate infusion from 51.5 +/- 2.0 to 38.6 +/- 3.3 microM but did not change significantly during lactate infusion. Intracellular free [Mg2+] fell from 705 +/- 53 to 498 +/- 30 microM at the highest pyruvate infusion and from 692 +/- 112 to 417 +/- 19 microM with lactate infusion. Extraction of both substrates was linear at low concentrations, reaching 0.56 mumol lactate.min-1.g wet wt-1 at 17.5 mM blood lactate and 0.58 mumol pyruvate.min-1.g wet wt-1 at 5.3 mM plasma pyruvate. Therefore, lactate uptake was almost five times lower than pyruvate uptake at similar concentrations. Elevated pyruvate (> 3 mM) resulted in almost complete inhibition of net lactate uptake. Infused [3-13C]lactate or -pyruvate gave rise to labeled glutamate and alanine in vivo, but labeled lactate was not visible when [3-13C]pyruvate was the substrate. The 13C enrichment of myocardial lactate was similar to alanine and acetyl CoA with infused [3-13C]lactate but was only one-half that of alanine and acetyl CoA when [3-13C]-pyruvate was the substrate, indicating a possible inhibition of lactate dehydrogenase.
Laughlin
M R
MR
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Taylor
J
J
Chesnick
A S
AS
DeGroot
M
M
Balaban
R S
RS
D000818:Animals; D002247:Carbon Isotopes; D004285:Dogs; D004734:Energy Metabolism; D005260:Female; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid
D002247:Carbon Isotopes; D007773:Lactates; D010710:Phosphates; D011773:Pyruvates; D010758:Phosphorus; D019344:Lactic Acid; D019289:Pyruvic Acid