Lactate dehydrogenase

Lactate dehydrogenase (LDH) is an enzyme (EC 1.1.1.27) present in a wide variety of organisms, including plants and animals.

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Reactions

It catalyses the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD⁺. At high concentrations of lactate, the enzyme exhibits feedback inhibition and the rate of conversion of pyruvate to lactate is decreased.

It also catalyzes the dehydrogenation of 2-Hydroxybutyrate, but it is a much poorer substrate than lactate. There is little to no activity with beta-hydroxybutyrate.

Enzyme isoforms

• LDH-1 (4H) - in the heart
• LDH-2 (3H1M) - in the reticuloendothelial system
• LDH-3 (2H2M) - in the lungs
• LDH-4 (1H3M) - in the kidneys
• LDH-5 (4M) - in the liver and striated muscle

The five isozymes that are usually described in the literature each contain four subunits. The major isozymes of skeletal muscle and liver, M₄, has four muscle (M) subunits; while H (heart)₄ is the main isozymes for heart muscle in most species, containing 4 H subunits. The other variants contain both types of subunits.

Usually LDH-2 is the predominant form in the serum. A LDH-1 level higher than the LDH-2 level (a "flipped pattern"), suggests myocardial infarction (damage to heart tissues releases heart LDH, which is rich in LDH-1, into the bloodstream). The use of this phenomenon to diagnose infarction has been largely superseded by the use of Troponin I or T measurement.

Genetics in Humans

The M and H subunits are encoded by two different genes:

• The M subunit is encoded by LDHA, located on chromosome 11p15.4 (Online 'Mendelian Inheritance in Man' (OMIM) 150000)
• The H subunit is encoded by LDHB, located on chromosome 12p12.2-p12.1 (Online 'Mendelian Inheritance in Man' (OMIM) 150100)
• A third isoform, LDHC or LDHX, is expressed only in the testis (Online 'Mendelian Inheritance in Man' (OMIM) 150150); its gene is likely a duplicate of LDHA and is also located on the eleventh chromosome (11p15.5-p15.3)

Mutations of the M subunit have been linked to the rare disease exertional myoglobinuria (see OMIM article), and mutations of the H subunit have been described but do not appear to lead to disease.

Medical use

Hemolysis

In medicine, LDH is often used as a marker of tissue breakdown as LDH is abundant in red blood cells and can function as a marker for hemolysis. A blood sample that has been handled incorrectly can show false-positively high levels of LDH due to erythrocyte damage.

It can also be used as a marker of myocardial infarction. Following a myocardial infarction, levels of LDH peak at 3-4 days and remain elevated for up to 10 days. In this way, elevated levels of LDH can be useful for determining if a patient has had a myocardial infarction if they come to doctors several days after an episode of chest pain.

Tissue turnover

Other uses are assessment of tissue breakdown in general; this is possible when there are no other indicators of hemolysis. It is used to follow-up cancer (especially lymphoma) patients, as cancer cells have a high rate of turnover with destroyed cells leading to an elevated LDH activity.

Exudates and transudates

Measuring LDH in fluid aspirated from a pleural effusion (or pericardial effusion) can help in the distinction between exudates (actively secreted fluid, e.g. due to inflammation) or transudates (passively secreted fluid, due to a high hydrostatic pressure or a low oncotic pressure). LDH is elevated (>200 U/l) in an exudate and low in a transudate. In empyema, the LDH levels generally will exceed 1000 U/l.

Meningitis and encephalitis

The enzyme is also found in cerebrospinal fluid where high levels of lactate dehydrogenase in cerebrospinal fluid are often associated with bacterial meningitis. High levels of the enzyme can also be found in cases of viral meningitis, generally indicating the presence of encephalitis and poor prognosis.

HIV and elevated LDH

LDH is often measured in HIV patients as a non-specific marker for Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP). Elevated LDH in the setting of upper respiratory symptoms in an HIV patient suggests, but is not diagnostic for, PCP.

See also

• Oxidoreductase
• Dehydrogenase

References

• IUBMB entry for 1.1.1.27
• BRENDA references for 1.1.1.27 (Recommended.)
• PubMed references for 1.1.1.27
• PubMed Central references for 1.1.1.27
• Google Scholar references for 1.1.1.27

• KEGG entry for 1.1.1.27

• BRENDA entry for 1.1.1.27

• NiceZyme view of 1.1.1.27

• EC2PDB: PDB structures for 1.1.1.27

• PRIAM entry for 1.1.1.27

• PUMA2 entry for 1.1.1.27

• IntEnz: Integrated Enzyme entry for 1.1.1.27

• MetaCyc entry for 1.1.1.27

• Atomic-resolution structures of enzymes belonging to this class