Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UDPGT or UGT) is a microsomal

glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic gl ...

() that catalyzes the transfer of the glucuronic acid component of

UDP-glucuronic acid UDP-glucuronic acid is a sugar used in the creation of polysaccharides and is an intermediate in the biosynthesis of ascorbic acid (except in primates and guinea pigs). It also participates in the heme degradation process of human. It is made fro ...

to a small hydrophobic molecule. This is a

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...

reaction. ''Alternative names:'' * glucuronyltransferase * UDP-glucuronyl transferase * UDP-GT

Function

Glucuronosyltransferases are responsible for the process of

, a major part of

phase II metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances. UGT is present in humans, other animals, plants, and bacteria. Famously, UGT enzymes are not present in the genus ''

Felis ''Felis'' is a genus of small and medium-sized cat species native to most of Africa and south of 60° latitude in Europe and Asia to Indochina. The genus includes the domestic cat. The smallest of the seven ''Felis'' species is the black-footed ...

'', and this accounts for a number of unusual toxicities in the cat family. The glucuronidation reaction consists of the transfer of the glucuronosyl group from uridine 5'-diphospho-glucuronic acid (UDPGA) to

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

molecules that contain oxygen, nitrogen, sulfur or carboxyl functional groups. The resulting

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...

is more polar (e.g. hydrophilic) and more easily excreted than the substrate molecule. The product solubility in blood is increased allowing it to be eliminated from the body by the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

Diseases

A deficiency in the

bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...

specific form of glucuronosyltransferase is thought to be the cause of

Gilbert's syndrome Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority resulting in higher levels in the blood. Many people never have symptoms. Occasionally jaundice (a yellowing of the ...

, which is characterized by unconjugated hyperbilirubinemia. It is also associated with

Crigler–Najjar syndrome Crigler–Najjar syndrome is a rare inherited autosomal recessive disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells. The disorder results in a form of non hemolytic jaundice, whic ...

, a more serious disorder where the enzyme's activity is either completely absent (Crigler–Najjar syndrome type I) or less than 10% of normal (type II). Infants may have a developmental deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug

chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...

which requires glucuronidation. This leads to a condition known as

gray baby syndrome Gray baby syndrome (also termed gray syndrome or grey syndrome) is a rare but serious, even fatal, side effect that occurs in newborn infants (especially premature babies) following the accumulation of the antibiotic chloramphenicol. Chlorampheni ...

Causes

Causes of unconjugated hyperbilirubinemia are divided into three main categories, namely, excessive

synthesis, liver bilirubin uptake malfunction, and bilirubin conjugation compromise. As to excessive bilirubin synthesis, both

intravascular hemolysis Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbi ...

and

extravascular hemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo ...

can involve in the pathophysiology. Additionally,

dyserythropoiesis Dyserythropoiesis refers to the defective development of red blood cells, also called erythrocytes. This problem can be congenital, acquired, or inherited. Some red blood cells may be destroyed within the bone marrow during the maturation process, ...

and extravasation of

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

into tissues such as

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

and

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

can also lead to indirect hyperbilirubinemia, along with

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

-induced,

ethinyl estradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological dis ...

chronic hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

, and

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

that are, otherwise, attributed to hepatic bilirubin mal-uptake and bilirubin conjugation compromise, respectively.

Genes

Human genes which encode UGT enzymes include: *

B3GAT1 3-beta-glucuronosyltransferase 1 (B3GAT1) is an enzyme that in humans is encoded by the ''B3GAT1'' gene, whose enzymatic activity creates the CD57 epitope on other cell surface proteins. In immunology, the CD57 antigen (CD stands for cluster of d ...

B3GAT2 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 is an enzyme that in humans is encoded by the ''B3GAT2'' gene. The product of this gene is a transmembrane protein belonging to the glucuronyltransferase family, and catalyzes th ...

B3GAT3 Beta-1,3-Glucuronyltransferase 3 is an enzyme that in humans is encoded by the ''B3GAT3'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DN ...

UGT1A1 UDP-glucuronosyltransferase 1-1, also known as UGT-1A, is an enzyme that in humans is encoded by the ''UGT1A1'' gene. UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT or UGT), an enzyme of the glucuroni ...

UGT1A3 UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the ''UGT1A3'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, ...

UGT1A4 UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the ''UGT1A4'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, ...

, UGT1A5,

UGT1A6 UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the ''UGT1A6'' gene. Function UDP-glucuronosyltransferase 1-6 is a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophil ...

, UGT1A7, UGT1A8,

UGT1A9 UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the ''UGT1A9'' gene. Function This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, suc ...

UGT1A10 UDP-glucuronosyltransferase 1-10 is an enzyme that in humans is encoded by the ''UGT1A10'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in D ...

UGT2A1 UDP glucuronosyltransferase 2 family, polypeptide B1, also known as UGT2B1, is an enzyme that in humans is encoded by the ''UGT2B1'' gene. Function The olfactory neuroepithelium, which lines the posterior nasal cavity, is exposed to a wide r ...

UGT2A2 UDP glucuronosyltransferase 2 family, polypeptide A2, also known as UGT2A2, is an enzyme that in humans is encoded by the ''UGT2A2'' gene. Function The olfactory neuroepithelium, which lines the posterior nasal cavity, is exposed to a wide ra ...

, UGT2A3,

UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4, also known as UGT2B4, is an enzyme that in humans is encoded by the ''UGT2B4'' gene. Function UGT2B4 is mainly involved in the glucuronidation of hyodeoxycholic acid, a bile acid, and catec ...

UGT2B7 UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltran ...

, UGT2B10, UGT2B11, UGT2B15,

UGT2B17 UDP-glucuronosyltransferase 2B17 is an enzyme that in humans is encoded by the ''UGT2B17'' gene. UGT2B17 belongs to the family of UDP-glucuronosyltransferases (UGTs; EC 2.4.1.17), enzymes that catalyze the transfer of glucuronic acid from uridine ...

, UGT2B28

References

External links

* {{Portal bar, Biology, border=no Transferases EC 2.4.1