It converts pyruvate, the final product of glycolysis, to lactate when oxygen is absent or in short supply, and it performs the reverse reaction during the Cori cycle in the liver.

LDH in humans uses His(193) as the proton acceptor, and works in unison with the coenzyme (Arg99 and Asn138), and substrate (Arg106; Arg169; Thr248) binding residues.

The two most common subunits are the LDH-M and LDH-H peptides, named for their discovery in muscle and heart tissue, and encoded by the LDHA and LDHB genes, respectively.

The increased NADH/NAD+ ratio also can cause hypoglycemia in an (otherwise) fasting individual who has been drinking and is dependent on gluconeogenesis to maintain blood glucose levels.

This lack of a functional subunit reduces the amount of enzyme formed, leading to an overall decrease in activity.

During the anaerobic phase of glycolysis (the Cori cycle), the mutated enzyme is unable to convert pyruvate into lactate to produce the extra energy the cells need.

The process of rhabdomyolysis also releases myoglobin into the blood, which will eventually end up in the urine and cause it to become red or brown: another condition known as myoglobinuria.

[19] In order to obtain a definitive diagnosis, a muscle biopsy may be performed to confirm low or absent LDH activity.

With lactate dehydrogenase-B deficiency, the highest concentration of B subunits can be found within the cardiac muscle, or the heart.

However, unlike lactate dehydrogenase-A deficiency, this mutation does not appear to cause any symptoms or health problems linked to this condition.

The onset of acidosis during periods of intense exercise is commonly attributed to accumulation of hydrogens that are dissociated from lactate.

From this reasoning, the idea of lactate production being a primary cause of muscle fatigue during exercise was widely adopted.

The lactate-forming reaction generates cytosolic NAD+, which feeds into the glyceraldehyde 3-phosphate dehydrogenase reaction to help maintain cytosolic redox potential and promote substrate flux through the second phase of glycolysis to promote ATP generation.

The production and removal of lactate from the cell also ejects a proton consumed in the LDH reaction- the removal of excess protons produced in the wake of this fermentation reaction serves to act as a buffer system for muscle acidosis.

[citation needed] Once proton accumulation exceeds the rate of uptake in lactate production and removal through the LDH symport,[24] muscular acidosis occurs.

On blood tests, an elevated level of lactate dehydrogenase usually indicates tissue damage, which has multiple potential causes, reflecting its widespread tissue distribution: Low and normal levels of LDH do not usually indicate any pathology.

[28] Low levels may be caused by large intake of vitamin C. LDH is a protein that normally appears throughout the body in small amounts.

Noncancerous conditions that can raise LDH levels include heart failure, hypothyroidism, anemia, pre-eclampsia, meningitis, encephalitis, acute pancreatitis, HIV and lung or liver disease.

A blood sample that has been handled incorrectly can show false-positively high levels of LDH due to erythrocyte damage.

LDH is often measured in HIV patients as a non-specific marker for pneumonia due to Pneumocystis jirovecii (PCP).

Elevated LDH in the setting of upper respiratory symptoms in a HIV patient suggests, but is not diagnostic for, PCP.

High levels of lactate dehydrogenase in cerebrospinal fluid are often associated with bacterial meningitis.

[37] In the case of viral meningitis, high LDH, in general, indicates the presence of encephalitis and poor prognosis.

LDH A and the possibility of inhibiting its activity has been identified as a promising target in cancer treatments focused on preventing carcinogenic cells from proliferating.

Chemical inhibition of LDH A has demonstrated marked changes in metabolic processes and overall survival of carcinoma cells.

Expression of LDH5 and VEGF in tumors and the stroma has been found to be a strong prognostic factor for diffuse or mixed-type gastric cancers.