PHAR 315 Lecture Notes - Lecture 4: Enterohepatic Circulation, Sulfatase, Glucuronidation
23 Feb 2016
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Conjugation with amino acids (glycine, taurine, glutamic acid) Function: xenobiotic metabolism and steroid/thyroid hormone metabolism and regulation. Subfamilies: ugt1a (9 isoforms), ugt2a (2 isoforms), and ugt2b (7 isoforms). 12 isoforms are in the liver, 3 have no known substrates. Most isoforms have overlapping affinity for substrates, but there are specificities: Function: conjugates sulfur onto hormones, peptides, drugs, and environmental chemicals (the sulfur is from the co-factor 3"-phosphoadenosine-3"- phosphosulfate (paps)) Both sult and ars are for steroid hormone balance/metabolism. Sults stop intracellular actions and help eliminate sex steroids, thyroid hormones, and adrenosteroids. Subfamilies: sult1 (8 isoforms), sult2 (3 isoforms), and sult4 (2 isoforms) Glucuronidase cleaves the -d-linkage back to the parent compounds. Balance of ugt to -glucuronidase can determine enterohepatic recirculation and clearance of the drug: Activity of -glucuronidase is high at birth and decreases to adult levels by 4 months.
