Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the ''LDHA''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
It is a monomer of
lactate dehydrogenase
Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvic acid, pyruvate to lactic acid, lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that t ...
, which exists as a
tetramer
A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...
. The other main subunit is
lactate dehydrogenase B (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 ...
and L-
lactate with concomitant inter-conversion of NADH and
NAD+. LDHA is found in most somatic tissues, though predominantly in
muscle tissue
Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to contract. ...
and tumors, and belongs to the
lactate dehydrogenase
Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvic acid, pyruvate to lactic acid, lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that t ...
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
Myoglobinuria is the presence of myoglobin in the urine, which usually results from rhabdomyolysis or muscle injury. Myoglobin is present in muscle cells as a reserve of oxygen.
Signs and symptoms
Signs and symptoms of myoglobinuria are usua ...
.
Interactive pathway map
LDHA Inhibitors
The following compounds have been demonstrated to
inhibit the LDHA enzyme:
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Oxamate
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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 it ...
*
Quinoline 3-sulfonamide
*
CHK-336
CHK-336 is a small molecule lactate dehydrogenase inhibitor developed by Chinook Therapeutics (a Novartis Company). CHK-336 is a first-in-class, orally available, and liver-targeted molecule and is being investigated for the treatment of primary hy ...
References
Further reading
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External links
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{{PDB Gallery, geneid=3939
Genes mutated in mice