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.
Highlights
Lactate dehydrogenase (LDH) is an essential enzyme in most living cells[1,2], which catalyzes the mutual transformation between pyruvate and lactate, associated with NADH and NAD þ interconversion[3] (Figure 1)
Because cancer cells heavily rely on aerobic glycolysis to support their growth, LDH comes to be an emerging anticancer target for cancer diagnosis and treatment[4]
From 1997 to 2016, approximately 1625 publications are found as LDH kinetic related, based on our query and manual filtration on a peerreviewed literature database named as ScopusVR
Summary
Lactate dehydrogenase (LDH) is an essential enzyme in most living cells[1,2], which catalyzes the mutual transformation between pyruvate and lactate, associated with NADH and NAD þ interconversion[3] (Figure 1). To inhibit the glycolysis within cancer cells, hundreds of small molecules are under study to reduce LDH activity. One type of inhibitor candidates are molecules that have similar chemical structures as pyruvate and are able to competitively associate on the substrate domain. Oxamate derivatives (Figure 2), e.g. are one type of model inhibitors[7]. These molecules are able to seize the available substrate-binding sites and further inhibit substrate binding and reactivity. A universal method to quantitatively describe the kinetic properties of LDH and evaluate the effect of inhibitors and temperature can be beneficial for cancer study
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Enzyme Inhibition and Medicinal Chemistry
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
