The glucuronidation is an important mechanism of cellular detoxification. It consists of the transfer of a glucuronic acid molecule to a great variety of toxic compounds for the cell, in order to facilitate its rapid elimination.
It is considered a metabolic pathway for biotransformation, as it involves the conversion of a substrate into a structurally modified chemical that has different biochemical properties. This transformation occurs through one or more chemical reactions catalyzed by enzymes called transferases.
This detoxification pathway is carried out by a wide group of organisms that includes animals, plants and bacteria. In each of them, the final elimination of the glycunorilated compounds occurs through different final excretion processes.
Since glucuronidation increases the solubility of compounds in aqueous media, it is also a driving mechanism and an enhancer for the rapid distribution of signaling metabolites such as hormones.
Cellular detoxification reactions
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Glucuronidation is one of the most important phase II reactions. It participates in the elimination of a large number of endogenous metabolites such as bilirubin and a wide range of xenobiotics, by transforming the latter into water-soluble compounds.
The glucuronidation chemical reaction consists of the transfer or binding of a glucuronic acid molecule to compounds of low water solubility that have chemical binding points in their structure. The product resulting from this reaction is called the glucuronide conjugate.
There are a wide variety of functional chemical groups that can be conjugated with glucuronic acid to generate glucuronides. Some of them are those rich in oxygen, sulfur, carbon and nitrogen atoms.
Glucuronides produced in mammals are eliminated in the urine or bile, whereas in unicellular organisms such as bacteria this elimination occurs simply by facilitated diffusion through the membrane. For this reason this mechanism is considered a detoxification process.
Since this process is essential for the maintenance of cellular homeostasis, in addition to ensuring the rapid distribution of compounds throughout the body (thus increasing their availability), it has become the focus of numerous pharmacological investigations.
Transferases
All enzymes that carry out reactions that involve the transfer of a functional group are known as transferases. The enzymatic glucuronidation reaction is catalyzed by a particular family of transferases that have been referred to as UDP-glucuronosyltrasferases (UGT).
The genes that code for UGTs have been found in complex organisms such as animals and plants as well as in bacteria. Thus, this widely distributed metabolic process may have originated in bacteria as a primitive mechanism for cellular elimination and / or excretion.
Genetic research has shown that in many organisms, the bank of the different UGT isoforms are encoded by genes whose sequences are highly conserved in bacteria, plants and animals.
In fact, a whole different UGT family may be encoded by a single gene that is read in multiple combinations to give rise to different protein products.
Routes of elimination of glucuronylated compounds
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