UGT2B17

Meaning

UGT2B17, or UDP-glucuronosyltransferase 2 family, polypeptide B17, is an enzyme central to human metabolism. It performs glucuronidation, a critical phase II detoxification. This protein conjugates endogenous steroid hormones, notably androgens like testosterone, making them water-soluble for efficient elimination.

Context

This enzyme belongs to the UDP-glucuronosyltransferase (UGT) superfamily, primarily expressed in the liver. UGT2B17 is also found in kidneys, small intestine, and prostate. It contributes significantly to regulating and clearing circulating steroid levels, directly influencing hormonal balance.

Significance

Genetic variations in the UGT2B17 gene, notably a common deletion, impact androgen metabolism. This deletion reduces enzyme activity, slowing testosterone glucuronidation. Affected individuals may exhibit higher circulating free, active androgens, influencing prostate health and testosterone interpretation in athletic anti-doping surveillance.

Mechanism

UGT2B17 catalyzes glucuronic acid transfer from UDP-glucuronic acid (UDP-GA) to a target steroid, like testosterone. This reaction forms a glucuronide conjugate. Its increased polarity and water solubility enable efficient excretion, primarily via urine, effectively deactivating the parent steroid’s hormonal signal.

Application

Clinical UGT2B17 knowledge extends to pharmacogenomics, predicting responses to drugs metabolized by this enzyme. In sports medicine, genetic testing for UGT2B17 deletion helps clarify urinary testosterone-to-epitestosterone (T/E) ratios, differentiating natural metabolic profiles from exogenous androgen administration. This informs clinical and sports authority decisions.

Metric

UGT2B17 status assessment relies primarily on genetic testing, such as PCR, to identify the common gene deletion. Indirectly, urinary steroid profiles, specifically the testosterone glucuronide to epitestosterone glucuronide ratio, indicate UGT2B17 activity; a low ratio often correlates. Direct enzyme activity measurement is typically a research tool.

Risk

Individuals with the UGT2B17 gene deletion may experience altered endogenous androgen clearance, potentially leading to persistently higher active testosterone levels. This metabolic difference might influence susceptibility to certain androgen-related health conditions or modify therapeutic responses. In athletics, misinterpreting T/E ratios without considering UGT2B17 genotype can lead to incorrect doping conclusions, emphasizing comprehensive assessment.

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