A mechanistic kinetic description of lactate dehydrogenase elucidating cancer diagnosis and inhibitor evaluation

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 32; no. 1; pp. 564 - 571
• Main Authors: Tang, Peifeng, Xu, Jianlin, Oliveira, Christopher L., Li, Zheng Jian, Liu, Shijie
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2017; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Cancer; Cancer diagnosis; Dehydrogenases; Diagnosis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Enzymes; Glycolysis; Humans; inhibitor evaluation; kinetic model; Kinetics; L-Lactate dehydrogenase; L-Lactate Dehydrogenase - antagonists & inhibitors; L-Lactate Dehydrogenase - metabolism; lactate dehydrogenase; Lactic acid; Medical diagnosis; Molecular Dynamics Simulation; Neoplasms - diagnosis; Neoplasms - enzymology; Neoplasms - metabolism; oligomeric enzyme; Temperature; Temperature effects; lactate dehydrogenase; inhibitor evaluation; oligomeric enzyme; Cancer diagnosis; kinetic model
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2016.1275606

As a key enzyme for glycolysis, lactate dehydrogenase (LDH) remains as a topic of great interest in cancer study. Though a number of kinetic models have been applied to describe the dynamic behavior of LDH, few can reflect its actual mechanism, making it difficult to explain the observed substrate and competitor inhibitions at wide concentration ranges. A novel mechanistic kinetic model is developed based on the enzymatic processes and the interactive properties of LDH. Better kinetic simulation as well as new enzyme interactivity information and kinetic properties extracted from published articles via the novel model was presented. Case studies were presented to a comprehensive understanding of the effect of temperature, substrate, and inhibitor on LDH kinetic activities for promising application in cancer diagnosis, inhibitor evaluation, and adequate drug dosage prediction.