The Biochemical and Clinical Perspectives of Lactate Dehydrogenase: An Enzyme of Active Metabolism

Abstract

Background: Lactate dehydrogenase (LDH) is a group of oxidoreductase isoenzymes catalyzing the reversible reaction between pyruvate and lactate. The five isoforms of this enzyme, formed from two subunits, vary in isoelectric points and these isoforms have different substrate affinity, inhibition constants and electrophoretic mobility. These diverse biochemical properties play a key role in its cellular, tissue and organ specificity. Though LDH is predominantly present in the cytoplasm, it has a multi-organellar location as well.

Objective: The primary objective of this review article is to provide an update in parallel, the previous and recent biochemical views and its clinical significance in different diseases.

Methods: With the help of certain inhibitors, its active site three-dimensional view, reactions mechanisms and metabolic pathways have been sorted out to a greater extent. Overexpression of LDH in different cancers plays a principal role in anaerobic cellular metabolism, hence several inhibitors have been designed to employ as novel anticancer agents.

Discussion: LDH performs a very important role in overall body metabolism and some signals can induce isoenzyme switching under certain circumstances, ensuring that the tissues consistently maintain adequate ATP supply. This enzyme also experiences some posttranslational modifications, to have diversified metabolic roles. Different toxicological and pathological complications damage various organs, which ultimately result in leakage of this enzyme in serum. Hence, unusual LDH isoform level in serum serves as a significant biomarker of different diseases.

Conclusion: LDH is an important diagnostic biomarker for some common diseases like cancer, thyroid disorders, tuberculosis, etc. In general, LDH plays a key role in the clinical diagnosis of various common and rare diseases, as this enzyme has a prominent role in active metabolism.

Keywords: Isoenzymes; Lactate dehydrogenase; clinical significance; enzyme inhibitors; isoenzyme switching; enzyme kinetics; post-translational modifications.