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

Abstract

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.

Signal-enhanced real-time magnetic resonance of enzymatic reactions at millitesla fields

“…Evaluating the kinetics of pyruvate to lactate have been a challenging task in pure enzymatic reactions with LDH over the past decades. 49 Fortunately, no substrate inhibition under our conditions were operative because the pyruvate is freshly generated by hydrolysis and has no time to form a ternary complex with NAD+ and LDH during 16 s of the overall enzymatic reaction time. 50 At low concentrations, first order reaction takes place according to the Michaelis–Menten equation.…”

Lactate dehydrogenase C4 (LDH-C4) is essential for the sperm count and motility: A case-control study

“…8 On the other hand, the sperm motility depends on the amount of energy produced by anaerobic glycolysis, aerobic glycolysis, and beta-oxidation of endogenous substrates. 9,10 Fructose is hexose secreted from seminal vesicles that can be used as an energy substrate for spermatozoa in anaerobic glycolysis to release lactic acid by the LDH activity. 4,7 Figure 1 Scheme of mutual transformation of pyruvate and lactate catalyzed by LDH .…”

“…4,7 Figure 1 Scheme of mutual transformation of pyruvate and lactate catalyzed by LDH . 9 The basic concept of enzyme-kinetics is expressed via the Michaelis Menten equation, which is derived from the generally accepted assumption that enzyme catalyzed reactions involve the formation of an enzyme-substrate complex. 9 Leonor Michaelis and Maude Menten suggested a simple model for most of the features of enzyme stimulates reactions.…”

“…9 The basic concept of enzyme-kinetics is expressed via the Michaelis Menten equation, which is derived from the generally accepted assumption that enzyme catalyzed reactions involve the formation of an enzyme-substrate complex. 9 Leonor Michaelis and Maude Menten suggested a simple model for most of the features of enzyme stimulates reactions. 11 In this model, the enzyme reversibly joins with its substrate to form an enzyme-substrate (ES) complex then yields product and regenerate the free enzyme.…”

Serum and salivary levels of lactate dehydrogenase in oral squamous cell carcinoma, oral lichen planus and oral lichenoid reaction

“…LDH is a biomarker for cancer detection, which is found in almost all cell types [ 2 ]. Increased serum levels of LDH isoenzymes have been reported in different cancer types such as the lung, breast, cervical, nasopharyngeal, hematopoietic, and stomach cancers [ 3 , 21 , 24 – 30 ]. Moreover, increased level of this tumor marker has been reported in malignant and premalignant oral lesions such as leukoplakia, submucosal fibrosis, and OLP, compared with normal tissue [ 2 , 21 , 30 , 31 ].…”