Aerobic lactate synthesis by cardiac muscle.
Cardiac lactate production under aerobic conditions is absolutely dependent upon the availability of extracellular pyruvate. In the steady state, aerobic lactate output is largely independent of cardiac work load, but increases slightly when octanoate is included in addition to pyruvate in the perfusion fluid. Transient episodes of supra-normal lactate production are seen after sudden increases in cardiac work output, and also after transitions from octanoate to pyruvate in the perfusion media. These pulses of lactate production are invariably associated with the slow activation of pyruvate dehydrogenase in response to a sudden change in cardiac metabolic state, and they are abolished by pre-perfusion with dichloracetate, which converts pyruvate dehydrogenase into the fully active form. A second, additional component of the lactate pulses is sensitive to pre-perfusion with the transaminase inhibitor aminooxyacetate. The size of the second component is markedly dependent upon the precise protocol adopted for the experiment, and these variations suggest that the second component is associated with a major redistribution of cardiac Krebs' cycle intermediates and amino acids following the initial exposure to pyruvate-containing media. Steadystate aerobic lactate production is insensitive to both dichloroacetate and aminooxyacetate, and is thought to result from a direct exchange of malate for oxaloacetate across the heart mitochondrial membranes.
D000332:Aerobiosis; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D007773:Lactates / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010477:Perfusion; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D002210:Caprylates; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D009243:NAD; D000625:Aminooxyacetic Acid; D003999:Dichloroacetic Acid