DEVELOPMENT OF HUMAN-LIVER UDP-GLUCURONOSYLTRANSFERASES

DEVELOPMENT OF HUMAN-LIVER UDP-GLUCURONOSYLTRANSFERASES
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DOI:
10.1159/000457587
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发表时间:
1989-01-01
期刊:
DEVELOPMENTAL PHARMACOLOGY AND THERAPEUTICS
影响因子:
--
通讯作者:
HUME, R
HUME, R
中科院分区:
其他
文献类型:
--
作者:
BURCHELL, B;COUGHTRIE, M;HUME, R

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在胎儿期和成人死后(死亡后不到5小时)肝脏样本中研究了对8种底物的多种UDPGT活性的发展。大多数胎仔和足月肝脏活性低于成人值的14%,但对5-羟色胺的活性除外,5-羟色胺存在于胎仔和足月肝脏中的成人水平。大多数UDPGT活性在出生后10-20周内发展到成人水平,甚至存活长达10周的早产儿(30周)也会发展这些酶活性。人肝微粒体的免疫印迹分析和人UDPGT的cDNA克隆显示了人中同工酶家族的存在,并且确定单个药物葡萄糖醛酸化酶在肝脏中的发育模式是重要的。发育中的肝脏的免疫印迹分析显示,胎儿肝脏中存在两种主要的UDPGT多肽,而在成人肝脏中观察到五种以上。通过在COS-7细胞中表达克隆基因和使用抗体来研究单个UDPGTs的底物特异性,将有助于鉴定围产期肝脏中存在的酶。
The development of multiple UDPGT activities towards eight substrates has been studied in fetal term and adult post-mortem (less than 5 h after death) liver samples. Most fetal and term liver activities were less than 14% of adult values, except that towards 5-hydroxytryptamine which was present in fetal and term liver at adult levels. The majority of UDPGT activities develop to adult levels within 10-20 weeks postnatally, and even premature(30 weeks) which survive for up to 10 weeks will develop these enzyme activities. Immunoblot analysis of human liver microsomes and cDNA cloning of human UDPGT shows the existence of the family of isoenzymes in man, and it is important to determine the developmental pattern of individual drug glucuronidating enzymes in liver. Immunoblot analysis of developing liver shows the presence of two major UDPGT polypeptides in fetal liver, whereas more than five are observed in adult liver. The investigation of substrate specificity of individual UDPGTs by expression of cloned genes in COS-7 cells and the use of antibodies will facilitate the identification of enzymes present in perinatal liver.