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Lactate dehydrogenase

 

 
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Lactate dehydrogenase
 
 
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Lactate dehydrogenase (LDH) is an enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
  present in a wide variety of organisms, including plants and animals.

atalyses the interconversion of pyruvate and lactate
Lactic acid

Lactic acid , also known as milk acid, is a chemical compound that plays a role in several biochemistry processes. It was first isolated in 1780 by a Swedish chemist, Carl Wilhelm Scheele, and is a carboxylic acid with a chemical formula of C3H6O3....
 with concomitant interconversion of NADH and NAD+
Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide, abbreviated NAD+, is a coenzyme found in all living cell s. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups: with one nucleotide containing an adenine base, and the other containing nicotinamide....
. It converts pyruvate, the final product of glycolysis
Glycolysis

Glycolysis is the metabolic pathway that converts glucose, C6H12O6, into pyruvate, C3H5O3-....
 to lactic acid when oxygen is absent or in short supply, and it performs the reverse reaction during the cori cycle
Cori cycle

The Cori cycle, named after its discoverers, Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactic acid produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is converted back to lactate....
 in the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
.






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Encyclopedia


Lactate dehydrogenase (LDH) is an enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
  present in a wide variety of organisms, including plants and animals.

Reactions

It catalyses the interconversion of pyruvate and lactate
Lactic acid

Lactic acid , also known as milk acid, is a chemical compound that plays a role in several biochemistry processes. It was first isolated in 1780 by a Swedish chemist, Carl Wilhelm Scheele, and is a carboxylic acid with a chemical formula of C3H6O3....
 with concomitant interconversion of NADH and NAD+
Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide, abbreviated NAD+, is a coenzyme found in all living cell s. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups: with one nucleotide containing an adenine base, and the other containing nicotinamide....
. It converts pyruvate, the final product of glycolysis
Glycolysis

Glycolysis is the metabolic pathway that converts glucose, C6H12O6, into pyruvate, C3H5O3-....
 to lactic acid when oxygen is absent or in short supply, and it performs the reverse reaction during the cori cycle
Cori cycle

The Cori cycle, named after its discoverers, Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactic acid produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is converted back to lactate....
 in the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
. At high concentrations of lactate, the enzyme exhibits feedback inhibition and the rate of conversion of pyruvate to lactate is decreased.

Ldh Reaction
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
Beta-hydroxybutyrate

beta-Hydroxybutyric acid is a ketone body. It is a chiral compound having two enantiomers, D-3-hydroxybutyric acid and L-3-hydroxybutyric acid....
.

Enzyme isoforms

  • LDH-1 (4H) - in the heart
    Heart

    The heart is a muscle organ in all vertebrates responsible for pumping blood through the blood vessels by repeated, rhythmic contractions, or a similar structure in annelids, mollusks, and arthropods....
  • LDH-2 (3H1M) - in the reticuloendothelial system
    Reticuloendothelial system

    The reticuloendothelial system , part of the immune system, consists of the phagocytosis cells located in reticular connective tissue, primarily monocytes and macrophages....
  • LDH-3 (2H2M) - in the lung
    Lung

    The lung is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart....
    s
  • LDH-4 (1H3M) - in the kidney
    Kidney

    The kidneys are Organ that have numerous biological roles. Their primary role is to maintain the homeostasis balance of bodily fluids by filtering and secreting Metabolomics#Metabolitess and minerals from the blood and excreting them, along with water , as urine....
    s
  • LDH-5 (4M) - in the liver
    Liver

    The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
     and striated muscle
    Striated muscle

    Striated muscle is a form of fibres that are combined into parallel fibres. More specifically, it can refer to:* Skeletal muscle* Cardiac muscle~cardiac referring to the heart....


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
Serum

Serum may refer to:*Blood plasma, with clotting factors removed*Antiserum, for transfer of passive immunity*Serous fluid, any clear bodily fluid...
. A LDH-1 level higher than the LDH-2 level (a "flipped pattern"), suggests myocardial infarction
Myocardial infarction

Myocardial infarction , commonly known as a heart attack, occurs when the Blood flow to part of the heart is interrupted. This is most commonly due to occlusion of a coronary artery following the rupture of a Vulnerable plaque, which is an unstable collection of lipids and white blood cells in the wall of an artery....
 (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
Troponin

Troponin is a complex of three regulatory proteins that is integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle....
 I or T measurement.

Genetics in Humans

The M and H subunits are encoded by two different gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
s:
  • The M subunit is encoded by LDHA, located on chromosome
    Chromosome

    A chromosome is an organized structure of DNA and protein that is found in Cell . A chromosome is a single piece of DNA that contains many genes, regulatory sequence and other genetic sequence....
     11p15.4
  • The H subunit is encoded by LDHB, located on chromosome 12p12.2-p12.1
  • A third isoform, LDHC or LDHX, is expressed only in the testis ; 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

Tissue breakdown elevates levels of LDH, and therefore a measure of it indicates e.g. hemolysis
Hemolysis

Hemolysis ?from the Greek Hemo-, Greek language meaning blood, -lysis, meaning to break open?is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
. Other disorders indicated by elevated LDH include cancer, meningitis, encephalitis, acute pancreatitis and HIV.

Hemolysis

In medicine
Medicine

Medicine is the art and science of healing. It encompasses a range of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, LDH is often used as a marker of tissue breakdown as LDH is abundant in red blood cell
Red blood cell

Red blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood....
s and can function as a marker for hemolysis
Hemolysis

Hemolysis ?from the Greek Hemo-, Greek language meaning blood, -lysis, meaning to break open?is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
. 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
Myocardial infarction

Myocardial infarction , commonly known as a heart attack, occurs when the Blood flow to part of the heart is interrupted. This is most commonly due to occlusion of a coronary artery following the rupture of a Vulnerable plaque, which is an unstable collection of lipids and white blood cells in the wall of an artery....
. 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
Necrosis

Necrosis is the name given to premature death of cell s and living biological tissue. Necrosis is caused by external factors, such as infection, toxins, or trauma....
 in general; this is possible when there are no other indicators of hemolysis
Hemolysis

Hemolysis ?from the Greek Hemo-, Greek language meaning blood, -lysis, meaning to break open?is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
. It is used to follow-up cancer
Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
 (especially lymphoma
Lymphoma

Lymphoma is a type of cancer that originates in lymphocytes of the immune system. They often originate in lymph nodes, presenting as an enlargement of the node ....
) patients, as cancer cell
Cancer Cell

Cancer Cell is the first Cell Press journal to focus on a specific disease field, with an editorial scope spanning from basic to clinical-oriented researches and a strong emphasis on translational research....
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
Pleural effusion

Pleural effusion is excess fluid that accumulates in the pleural cavity, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during inhalation....
 (or pericardial effusion
Pericardial effusion

Pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. Because of the limited amount of space in the pericardial cavity, fluid accumulation will lead to an increased intrapericardial pressure and this can negatively affect heart function....
) can help in the distinction between exudate
Exudate

An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. Its composition varies but generally includes water and the dissolved solutes of the blood, some or all blood protein, white blood cells, platelets and red blood cells....
s (actively secreted fluid, e.g. due to inflammation
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
) or transudate
Transudate

Transudate is extravascular fluid with low protein content and a low specific gravity <1.012. It has low nucleated cell counts and the primary cell types are mononuclear cells: macrophages, lymphocytes and mesothelia cells....
s (passively secreted fluid, due to a high hydrostatic pressure or a low oncotic pressure
Oncotic pressure

Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system....
). LDH is elevated (>200 U/l) in an exudate and low in a transudate. In empyema
Empyema

A pleural empyema is an accumulation of pus in the pleural cavity. Most pleural empyemas arise from an infection within the lung , often associated with parapneumonic effusions....
, the LDH levels generally will exceed 1000 U/l.

Meningitis and encephalitis

The enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 is also found in cerebrospinal fluid
Cerebrospinal fluid

Cerebrospinal fluid , Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain....
 where high levels of lactate dehydrogenase in cerebrospinal fluid are often associated with bacterial meningitis
Meningitis

Meningitis is a medical condition caused by inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges....
. High levels of the enzyme can also be found in cases of viral
Virus

A virus is a Optical microscope#Limitations of light microscopes infectious agent that is unable to grow or reproduce outside a host cell . Viruses infect all cellular life....
 meningitis, generally indicating the presence of encephalitis
Encephalitis

Not to be confused with syphilis, although that can cause encephalitis as well.Encephalitis is an Acute inflammation of the brain.Encephalitis with meningitis is known as meningoencephalitis....
 and poor prognosis
Prognosis

Prognosis is a medicine term denoting the Physician's prediction of how a patient will progress, and whether there is a chance of recovery. This word is often used in medical reports dictating a physician's view on a case....
.

HIV

LDH is often measured in HIV patients as a non-specific marker for pneumonia due to Pneumocystis jiroveci
Pneumocystis pneumonia

Pneumocystis pneumonia is a form of pneumonia caused by the yeast-like fungus, Pneumocystis jirovecii. This species of fungus is specific to humans....
 (PCP). Elevated LDH in the setting of upper respiratory symptoms in an HIV patient suggests, but is not diagnostic for, PCP. However, in HIV-positive patients with respiratory symptoms, a very high LDH level (>600 IU/L) indicated histoplasmosis
Histoplasmosis

Histoplasmosis, also known as Darling's disease,is a disease caused by the fungus Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease primarily affects the lungs....
 (9.33 more likely) in a study of 120 PCP and 30 histoplasmosis patients.

Dysgerminoma

Elevated LDH is often the first clinical sign of a dysgerminoma
Germinoma

A germinoma is a type of germ cell tumor which is not differentiated upon examination. It may be benign or malignant....
. Not all dysgerminomas produce LDH, and this is often a non-specific finding.

See also

  • Oxidoreductase
    Oxidoreductase

    In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule to another ....
  • Dehydrogenase
    Dehydrogenase

    A dehydrogenase is an enzyme that oxidizes a substrate by transferring one or more hydrides to an acceptor, usually Nicotinamide adenine dinucleotide/NADP or a flavin coenzyme such as FAD or FMN....


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