Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the ''LDHA'' gene. It is a monomer of Lactate dehydrogenase, which exists as a tetramer. The other main subunit is

lactate dehydrogenase B Lactate dehydrogenase B is a protein that in humans is encoded by the LDHB gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birt ...

(LDHB).

Function

Lactate dehydrogenase A catalyzes the inter-conversion of

pyruvate Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic aci ...

and L-

lactate Lactate may refer to: * Lactation, the secretion of milk from the mammary glands * Lactate, the conjugate base of lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with ...

with concomitant inter-conversion of NADH and NAD⁺. LDHA is found in most somatic tissues, though predominantly in muscle tissue and tumors, and belongs to the lactate dehydrogenase family. It has long been known that many human cancers have higher LDHA levels compared to normal tissues. It has also been shown that LDHA plays an important role in the development, invasion and metastasis of malignancies. Mutations in LDHA have been linked to exertional myoglobinuria.

Interactive pathway map

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of LDHA function. A conditional knockout mouse line, called ''Ldha^{tm1a(EUCOMM)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to crea ...

program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and five significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Animals of both sex had abnormal plasma chemistry, males also had improved

glucose tolerance Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...

and increased red blood cell distribution width.

LDHA Inhibitors

The following compounds have been demonstrated to inhibit the LDHA enzyme: * Oxamate *

Epigallocatechin gallate Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG – the most abundant catechin in tea – is a polyphenol under basic research for its ...

* Quinoline 3-sulfonamide

References

External links