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

Abstract

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

Keywords

• Malic enzyme
• Breast cancer
• Kinetics
• Cancer metabolism