Sauer 1978 Cancer Res

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Sauer LA, Dauchy RT (1978) Identification and properties of the nicotinamide adenine dinucleotide (phosphate)+-dependent malic enzyme in mouse ascites tumor mitochondria. Cancer Res 38:1751-6.

» PMID: 25711 Open Access

Sauer LA, Dauchy RT (1978) Cancer Res

Abstract: ELD, ELT/B1, Krebs II, and Sarcoma 180 ascites tumor cells were examined for the mitochondria! malic enzymes. The nicotinamide adenine dinucleotide (phosphate) [NAD(P)+]-dependent malic enzyme was present in all mitochondrial fractions at activities that ranged from 21 to 27 nmol reduced nicotinamide adenine dinucleotide formed per min per mg mitochondrial protein. As judged by kinetic properties, the enzyme was essentially identical in the different ascites tumors. Activity with both NAD+ and NADP+ was stimulated by fumarate and inhibited by adenosine 5'-triphosphate. In the presence of 5 mM fumarate, the apparent Km values for malate were about 2 mM with either NAD+ or NADP+ as coenzyme. The apparent Km values for NAD+ and NADP+ were approximately 60 µM, and NAD+ and NADP+ were shown to compete for reduction. The strictly NADP+ -linked mitochondrial isoenzyme was not detected in these ascites tumors. The strictly NADP+-dependent isoenzyme of the cytosol was present, but its kinetic properties were considerably different from those during NADP+ reduction via the mitochondrial NAD(P)+-dependent malic enzyme. Pyruvate was formed by ascites tumor mitochondria during malate-supported respiration. Phosphate, which stimulates malate entry via the inorganic orthophosphate-malate transporter, increased the rate of pyruvate accumulation. Pyruvate accumulation was inhibited by the addition of adenosine 5'-diphosphate, suggesting that pyruvate generated by the NAD(P)+-dependent malic enzyme was completely utilized by pyruvate dehydrogenase during State 3.

Labels: MiParea: Respiration  Pathology: Cancer 

Preparation: Isolated mitochondria, Enzyme 

Regulation: ADP, ATP production  Coupling state: LEAK, OXPHOS 

Malic enzyme 

  1. Malic enzyme 1: mt NADP+ dependent: (+)rat heart mt; (-)rat liver mt
  2. Malic enzyme 2: mt NAD(P)+ dependent: (-)rat heart mt; (-)rat liver mt; (+)ascites tumor
  3. Malic enzyme 3: cytosolic NAD(P)+ dependent: (-)ascites tumor