ugt1.pptx

ugt1 李磊郭娇胜郑俊健何俊浩何健深 Objectives: ● contribution,distribution,function ● the UGT family ● structure of ugt1 ● ic polymorphism and disease 1. Gilbert's syndrome 2. Crigler-Najjar syndrome ● laboratory experiments ? Distribution:UGT is widely distributed in the human body's various tissues, including kidney, brain, skin, intestines, spleen, thymus, heart, liver and small intestine in which the distribution of the highest . ? Function:UGT1 function is mainly concerned with the metabolism of various substances, UGT1 can catalyze a variety pounds and UDP- glucuronidation , the formation of glucuronide , pounds excreted through the bile or kidney. The ugt famiyl ugt 1 ugt1a1-ugt1a13 ugt ugt 2 ugt2a ugt2b ugt 8 ugt1 The gene complex ( 基因复合体) of ugt1 is subsist in chromosome (染色体) 2q37 ugt1a1 can be encoded with bilirubin (胆红素) as substrate (底物) ugt (b- ugt ) Ugt1a2-ugt1a5 encoding bile Red pigment-like substance (胆红素样物质) as substrate UGT structure of ugt1 UGT1 Protein carboxyl (羧基) coding exon 4, is the conservative (保守) UGT1 The substrate of the decision on properties of UGT1 isozymes ( ugt1 同工酶) ic polymorphism ? UGT is potentially of toxicological and physiological importance. ? Functional significance has only been convincingly demonstrated for ic polymorphism of UGT1A1. ? It has been proposed on the basis of altered catalytic activity of mutants of UGT 1A6, 1A7 and 2B15 that ic polymorphism of these forms may be of toxicological significance, but this is yet to be proven. 9 ic polymorphism and disease 1、 Gilbert's syndrome ? The mon hereditary cause of increased bilirubin . ? Found in up to 5% of the population. ? Caused by elevated levels of unconjugated bilirubin in the bloodstream hyperbilirubinemia . ? The source of this hyperbilirubinemia is reduced activity of the enzyme glucuronyltransferase which conjugate bilirubin and some other lipophilic molecules. 10 Gil