Glucuronidation enzymes, genes and psychiatry

Area of Science:

• Pharmacogenetics
• Drug Metabolism
• Biochemistry

Background:

• Phase I cytochrome P450 (CYP) enzymes are well-studied, while phase II UDP-glucuronosyltransferase (UGT) enzymes are less understood.
• UGTs produce water-soluble, less toxic metabolites, facilitating excretion.
• Reasons for UGT neglect include overlapping activity, complex cycles, and analytical challenges.

Purpose of the Study:

• To review the current understanding of UGT enzymes and their role in drug metabolism.
• To highlight the implications of UGT activity in psychiatric conditions.
• To use CYP knowledge as a model for UGT research advancement.

Main Methods:

• Review of existing literature on UGT enzymes and glucuronidation.
• Classification of human UGT genes into families (UGT1 and UGT2) and subfamilies.
• Discussion of UGT substrate specificities and tissue distribution.

Main Results:

• At least 24 human UGT genes identified, classified into UGT1 and UGT2 families.
• UGT1A subfamily (chromosome 2) metabolizes bilirubin, hormones, and medications (e.g., antidepressants, antipsychotics).
• UGT2B subfamily (chromosome 6) metabolizes steroids and bile acids; UGTs are involved in metabolizing certain anti-epileptics, opioids, and serotonin.

Conclusions:

• Glucuronidation by UGTs is critical for drug and endogenous compound metabolism.
• UGTs play a significant role in the pharmacokinetics of various medications relevant to psychiatry.
• UGTs may have neuroprotective functions, with implications for neurological and psychiatric disorders.