UGT1A1

UGT1A1 encodes an enzyme expressed largely in the liver, kidney, gut, prostate, ovary and breast tissue. It is responsible for the inactivation of molecules such as estrogen and other steroid hormones, thyroxine and common drugs such as morphine and acetaminophen (paracetamol), and bilirubin, preparing them for excretion via urine and bile. Variants in UGT1A1 can cause low enzyme function. Due to the bacterial production of an enzyme called beta-glucuronidase, intestinal dysbiosis can cause inactivated (conjugated) compounds to become reactivated (unconjugated) and re-released into circulation.

The protein produced from the UGT1A1 gene, called the bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme, is the only enzyme that glucuronidates bilirubin, a substance produced when red blood cells are broken down. This enzyme converts the toxic form of bilirubin (unconjugated bilirubin) to its non-toxic form (conjugated bilirubin), making it able to be dissolved and removed from the body.

The bilirubin-UGT enzyme is primarily found in cells of the liver, where bilirubin glucuronidation takes place. Conjugated bilirubin is dissolved in bile, a fluid produced in the liver, and excreted with solid waste.