This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Greenhouse, W. V. V. Articles by Lehninger, A. L. Search for Related Content PubMed PubMed Citation Articles by Greenhouse, W. V. V. Articles by Lehninger, A. L.

Occurrence of the Malate-Aspartate Shuttle in Various Tumor Types¹

Department of Physiological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addition of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrogenase in the cytoplasm.

¹ This work was supported in part by NIH Grant GM05919 and by Contract NO1-CP-45610 from the National Cancer Institute.

² Leukemia Society of America Special Fellow.

³ To whom requests for reprints should be sent.

Received 11/14/75. Accepted 1/ 5/76.

This article has been cited by other articles:

				M. Lane and D. K. Gardner Mitochondrial Malate-Aspartate Shuttle Regulates Mouse Embryo Nutrient Consumption J. Biol. Chem., May 6, 2005; 280(18): 18361 - 18367. [Abstract] [Full Text] [PDF]

				A. R. Salomon, D. W. Voehringer, L. A. Herzenberg, and C. Khosla Understanding and exploiting the mechanistic basis for selectivity of polyketide inhibitors of F0F1-ATPase PNAS, December 19, 2000; 97(26): 14766 - 14771. [Abstract] [Full Text] [PDF]