歧视Crigler-Najjar I和II型之间的表达突变胆红素尿苷diphosphate-glucuronosyltransferase。
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Seppen J, Bosma PJ Goldhoorn BG, CT,他Chowdhury JR Chowdhury NR,詹森PL, Oude Elferink RP
歧视Crigler-Najjar I和II型之间的表达突变胆红素尿苷diphosphate-glucuronosyltransferase。
中国投资。1994年12月,94 (6):2385 - 91。
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7989595 (在PubMed]
- 文摘
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Crigler-Najjar (CN)疾病分为两个亚型,类型I和II。这些类型之间的差异的分子基础是不清楚。几个突变胆红素UDP-glucuronosyl-transferase (B-UGT)基因的6个CN I型和两个CN II型患者确认。包含这些突变的重组cdna表达因为细胞。B-UGT活动测定用高效液相色谱法和表达蛋白质的数量使用夹心ELISA测定的数量。这使我们能够确定的具体活动表达的酶。所有类型的病人检查B-UGT1基因的突变,导致完全不活跃的酶。患者的B-UGT1基因的突变CN II型只是部分灭活酶。在饱和浓度的胆红素(75 microM) CN II型患者有4.4 + / - 2%的剩余活动和CN II型病人B 38 + / - 2%剩余活动。动力学常数的glucuronidation胆红素测定。 The affinities for bilirubin of B-UGT1 expressed in COS cells and B-UGT from human liver microsomes were similar with Km of 5.1 +/- 0.9 microM and 7.9 +/- 5.3 microM, respectively. B-UGT1 from patient B had a tenfold decreased affinity for bilirubin, Km = 56 +/- 23 microM. At physiological concentrations of bilirubin both type II patients will have a strongly reduced conjugation capacity, whereas type I patients have no B-UGT activity. We conclude that CN type I is caused by a complete absence of functional B-UGT and that in CN type II B-UGT activity is reduced.