The Kinetic Characteristics of Malic Enzyme in Human Breast Tissue Cancer Cell Lines MCF-7 and MDA-MB-231

Abstract

<strong>Background:</strong> A high level of replication is one of the main indicators of tumors.<br />Tumor cells have to manufacture and transport macromolecules into daughter cells. One<br />of the required enzymes is malic enzyme, which generates the NADPH for fatty acid<br />synthesis in order to make cell membrane and pyruvate, and support the glycolysis<br />pathway to supply the energy demand. Due to the enormous proliferation of cancer cells,<br />it is likely that the activity of malic enzyme in cancer cells is more than normal cells.<br />The aim of this study is to survey the kinetics of malic enzyme in tumor and normal<br />breast tissues.<br /><strong>Methods:</strong> We obtained the tumor and normal breast tissue specimens directly<br />from the operating room. The assays were performed with partially purified samples<br />under optimum conditions for the substrate and co-factor requirements. The velocity<br />of the enzyme or Michaelis-Menten constant, maximum velocity, and the amount of<br />inhibitor that reduced the enzyme activity by 50% were obtained and calculated in all<br />samples.<br /><strong>Results:</strong> The Michaelis-Menten constant for malate was lower in tumors compared<br />to normal samples. In contrast, the maximum velocity for malate in tumors was higher<br />than normal tissues, whereas the amount of inhibitor that reduced the enzyme activity<br />by 50% of guanidine hydrochloride and sodium chloride were both higher in tumors<br />than normal tissues.<br /><strong>Conclusion:</strong> The obtained results indicated that the malic enzyme kinetics had<br />different patterns in tumor tissues in comparison with normal tissues. A higher affinity<br />of malic enzyme for pyruvate production in tumors supported high aerobic glycolysis.<br />Moreover, it could be an approach to connect glutaminolysis to the glycolysis pathway.<br />Malic enzyme could be a target to inhibit the glycolysis and glutaminolysis pathways<br />in tumors.