glükuronülaatsioon

Glükuronülaatsioon, also known as glucuronidation, is a biochemical conjugation reaction that attaches glucuronic acid to various endogenous and exogenous compounds. The process is mediated by a family of enzymes called UDP‑glucuronosyltransferases (UGTs). During glucuronidation, UDP‑glucuronic acid serves as the glucuronic acid donor, and the acceptor typically contains a hydroxyl, carboxyl, or amino group. By forming a β‑O‑glucuronide or β‑N‑glucuronide linkage, the reaction markedly increases the hydrophilicity of the substrate, thereby enhancing its solubility in aqueous environments. This elevated solubility facilitates excretion via bile or urine and reduces the biological activity of potentially harmful substances.

Glucuronidation plays a crucial role in drug metabolism and detoxification. Many pharmaceuticals, including morphine, acetaminophen, and various antibiotics, undergo this modification before elimination. The reaction is considered a Phase II metabolic reaction, following an initial Phase I oxidation, reduction, or hydrolysis step that primes the molecule for conjugation. In addition to xenobiotics, endogenous hormones and metabolites such as estradiol, bilirubin, and bilirubin conjugates undergo glucuronidation, contributing to physiological regulation and homeostasis.

Clinical relevance arises from genetic polymorphisms in UGT genes, which can alter enzyme activity. Individuals with reduced glucuronidation capacity may experience altered drug efficacy or increased susceptibility to toxin accumulation. Diagnostic assays measuring glucuronide conjugates in biological fluids aid in monitoring drug disposition and metabolic disorders. The study of glucuronidation continues to inform pharmacology, toxicology, and the development of therapeutic agents.