View source for Lactate dehydrogenase

{{protein
| Name = lactate dehydrogenase A
| caption = 
| image = 
| width = 
| HGNCid = 6535
| Symbol = LDHA
| AltSymbols = 
| EntrezGene = 3939
| OMIM = 150000
| RefSeq = NM_005566
| UniProt = P00338
| PDB = 
| ECnumber = 1.1.1.27
| Chromosome = 11
| Arm = p
| Band = 15.4
| LocusSupplementaryData = 
}}
{{protein
| Name = lactate dehydrogenase B
| caption = 
| image = 
| width = 
| HGNCid = 6541
| Symbol = LDHB
| AltSymbols = 
| EntrezGene = 3945
| OMIM = 150100
| RefSeq = NM_002300
| UniProt = P07195
| PDB = 
| ECnumber = 1.1.1.27
| Chromosome = 12
| Arm = p
| Band = 12.2-12.1
| LocusSupplementaryData = 
}}
{{protein
| Name = lactate dehydrogenase C
| caption = 
| image = 
| width = 
| HGNCid = 6544
| Symbol = LDHC
| AltSymbols = 
| EntrezGene = 3948
| OMIM = 150150
| RefSeq = NM_002301
| UniProt = P07864
| PDB = 
| ECnumber = 1.1.1.27
| Chromosome = 11
| Arm = p
| Band = 15.5-15.3
| LocusSupplementaryData = 
}}
{{SI}}
{{CMG}}

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==Overview==
'''Lactate dehydrogenase''' ('''LDH''') is an [[enzyme]] ({{EC_number|1.1.1.27}}) present in a wide variety of organisms, including plants and animals. 

==Reactions==
It catalyses the interconversion of [[pyruvate]] and [[lactic acid|lactate]] with concomitant interconversion of NADH and [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]].  At high concentrations of lactate, the enzyme exhibits feedback inhibition and the rate of conversion of pyruvate to lactate is decreased.

[[Image:LDH_reaction.png|center|thumb|355px|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 ==
* LDH-1 (4H) - in the [[heart]]
* LDH-2 (3H1M) - in the [[reticuloendothelial system]]
* LDH-3 (2H2M) - in the [[lung]]s
* LDH-4 (1H3M) - in the [[kidney]]s
* 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, M<sub>4</sub>, has four muscle (M) subunits; while H (heart)<sub>4</sub> 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 [[gene]]s:
* The M subunit is encoded by ''LDHA'', located on [[chromosome]] 11p15.4 ({{OMIM|150000}})
* The H subunit is encoded by ''LDHB'', located on chromosome 12p12.2-p12.1 ({{OMIM|150100}})
* A third isoform, ''LDHC'' or ''LDHX'', is expressed only in the [[testis]] ({{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 cell]]s 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 [[necrosis|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 cell]]s 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 [[exudate]]s (actively secreted fluid, e.g. due to [[inflammation]]) or [[transudate]]s (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 [[bacterium|bacteria]]l [[meningitis]]. High levels of the enzyme can also be found in cases of [[virus|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)==
* [[Acute tubular necrosis]]
* Cardiac [[arrhythmia]]
* [[Cirrhosis]]
* [[Congestive Heart Failure]]
* [[Dermatomyositis]]
* [[Erythrocyte]] destruction from [[prosthetic heart valve]]
* [[Glomerulonephritis]]
* [[Hemolytic anemia]]
* [[Hepatic failure]]
* [[Hepatitis]]
* [[Hepatoma]]
* Infarction
* [[Infectious mononucleosis]]
* [[Ischemic colitis]]
* [[Kidney transplant]] rejection
* [[Leukemia]]
* [[Liver abscess]]
* [[Lymphoma]]
* [[Megaloblastic anemia]]
* [[Multiple Myeloma]]
* Muscular [[trauma]]
* [[Myocardial Infarction]]
* [[Myocarditis]]
* [[Myopathy]]
* [[Neuroblastoma]]
* Neurogenic muscular atrophy
* [[Pancreatitis]]
* [[Pneumonia]]
* [[Portal hypertension]]
* Postoperative
* Progressive [[muscular dystrophy]]
* [[Pulmonary embolism]]
* [[Testicular cancer]]

== See also ==
* [[Oxidoreductase]] 
* [[Dehydrogenase]]

==References==
{{reflist|1}}
{{Enzyme references|EC_number=1.1.1.27|IUBMB_EC_number=1/1/1/27}}

==External links==
{{Enzyme links|EC_number=1.1.1.27|IUBMB_EC_number=1/1/1/27}}

{{Alcohol oxidoreductases}}
{{Glycolysis enzymes}}
{{SIB}}

[[Category:Chemical pathology]]
[[Category:Tumor markers]]
[[Category:EC 1.1.1]]
[[Category:Blood tests]]
[[Category:Gastroenterology]]
[[Category:Cardiology]]
[[Category:Pulmonology]]

[[de:Laktatdehydrogenase]]
[[es:Lactato deshidrogenasa]]
[[fr:Lactate déshydrogénase]]
[[it:L-lattato deidrogenasi]]
[[nl:Melkzuurdehydrogenase]]
[[ja:乳酸脱水素酵素]]
[[ru:Лактатдегидрогеназа]]
[[fi:Laktaattidehydrogenaasi]]
[[zh:乳酸脱氢酶]]

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