Lactate dehydrogenase

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lactate dehydrogenase A
Identifiers
Symbol LDHA
Entrez 3939
HUGO 6535
OMIM 150000
RefSeq NM_005566
UniProt P00338
Other data
EC number 1.1.1.27
Locus Chr. 11 p15.4
lactate dehydrogenase B
Identifiers
Symbol LDHB
Entrez 3945
HUGO 6541
OMIM 150100
RefSeq NM_002300
UniProt P07195
Other data
EC number 1.1.1.27
Locus Chr. 12 p12.2-12.1
lactate dehydrogenase C
Identifiers
Symbol LDHC
Entrez 3948
HUGO 6544
OMIM 150150
RefSeq NM_002301
UniProt P07864
Other data
EC number 1.1.1.27
Locus Chr. 11 p15.5-15.3

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

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

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.

Catalytic function of LDH

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

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 The use of this phenomenon to diagnose infarction has been largely superseded by the use of Troponin I or T measurement.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:

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.

Complete Differential Diagnosis of an Elevated Lactate Dehydrogenase (LDH)

See also

References

External links

de:Laktatdehydrogenaseit:L-lattato deidrogenasi

nl:Melkzuurdehydrogenasefi:Laktaattidehydrogenaasi


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