Laughlin M R, Taylor J, Chesnick A S, DeGroot M, Balaban R S
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Physiol. 1993 Jun;264(6 Pt 2):H2068-79. doi: 10.1152/ajpheart.1993.264.6.H2068.
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.
丙酮酸比密切相关的底物L-乳酸更能显著提高灌注心脏中的磷酸化电位。因此,对完整犬心肌中这些化合物的代谢进行了研究。在血浆丙酮酸浓度为5.3 mM时,磷酸肌酸/三磷酸腺苷(Phosphocreatine/ATP)增加了23%,但乳酸除了在最高浓度(血液中17.5 mM)时外,并没有显著增加。在输注丙酮酸期间,计算得出的[二磷酸腺苷(ADP)]从51.5±2.0微摩尔降至38.6±3.3微摩尔,但在输注乳酸期间没有显著变化。在最高丙酮酸输注时,细胞内游离[镁离子(Mg2+)]从705±53微摩尔降至498±30微摩尔,在输注乳酸时从692±112微摩尔降至417±19微摩尔。两种底物在低浓度时的摄取呈线性,在血液乳酸浓度为17.5 mM时,乳酸摄取量达到0.56微摩尔·分钟-1·克湿重-1,在血浆丙酮酸浓度为5.3 mM时,丙酮酸摄取量达到0.58微摩尔·分钟-1·克湿重-1。因此,在相似浓度下,乳酸摄取量比丙酮酸摄取量低近五倍。丙酮酸浓度升高(>3 mM)导致净乳酸摄取几乎完全受到抑制。输注的[3-13C]乳酸或丙酮酸在体内产生了标记的谷氨酸和丙氨酸,但当以[3-13C]丙酮酸为底物时,未观察到标记的乳酸。输注[3-13C]乳酸时,心肌乳酸的13C富集与丙氨酸和乙酰辅酶A相似,但当以[3-13C]丙酮酸为底物时,仅为丙氨酸和乙酰辅酶A的一半,这表明乳酸脱氢酶可能受到抑制。