Genetics and pathophysiology of mammalian sulfate biology  

作　　者：Rachel Langford Elizabeth Hurrion Paul A. Dawson 

机构地区：[1]Mater Research Institute, University of Queensland, Woolloongabba, 4102, Queensland, Australia [2]Mater Mothers' Hospital, South Brisbane, 4101, Queensland, Australia

出　　处：《Journal of Genetics and Genomics》2017年第1期7-20,共14页遗传学报（英文版）

基　　金：supported by the Mater Medical Research Institute,Mater Foundation and a Mater Foundation Research Fellowship to PAD

摘　　要：Nutrient sulfate is essential for numerous physiological functions in mammalian growth and development. Accordingly, disruptions to any of the molecular processes that maintain the required biological ratio of sulfonated and unconjugated substrates are likely to have detrimental consequences for mammalian physiology. Molecular processes of sulfate biology can be broadly grouped into four categories： firstly, intracellular sulfate levels are maintained by intermediary metabolism and sulfate transporters that mediate the transfer of sulfate across the plasma membrane; secondly, sulfate is converted to 3＇-phosphoadenosine 5＇-phosphosulfate （PAPS）, which is the universal sulfonate donor for all sulfonation reactions; thirdly, sulfotransferases mediate the intracellular sulfonation of endogenous and exogenous substrates; fourthly, sulfate is removed from substrates via sulfatases. From the literature, we curated 91 human genes that encode all known sulfate transporters, enzymes in pathways of sulfate generation, PAPS synthetases and transporters, sulfotransferases and sulfatases, with a focus on genes that are linked to human and animal pathophysiology. The predominant clinical features linked to these genes include neurological dysfunction, skeletal dysplasias, reduced fecundity and reproduction, and cardiovascular pathologies. Collectively, this review provides reference information for genetic investigations of perturbed mammalian sulfate biology.Nutrient sulfate is essential for numerous physiological functions in mammalian growth and development. Accordingly, disruptions to any of the molecular processes that maintain the required biological ratio of sulfonated and unconjugated substrates are likely to have detrimental consequences for mammalian physiology. Molecular processes of sulfate biology can be broadly grouped into four categories： firstly, intracellular sulfate levels are maintained by intermediary metabolism and sulfate transporters that mediate the transfer of sulfate across the plasma membrane; secondly, sulfate is converted to 3＇-phosphoadenosine 5＇-phosphosulfate （PAPS）, which is the universal sulfonate donor for all sulfonation reactions; thirdly, sulfotransferases mediate the intracellular sulfonation of endogenous and exogenous substrates; fourthly, sulfate is removed from substrates via sulfatases. From the literature, we curated 91 human genes that encode all known sulfate transporters, enzymes in pathways of sulfate generation, PAPS synthetases and transporters, sulfotransferases and sulfatases, with a focus on genes that are linked to human and animal pathophysiology. The predominant clinical features linked to these genes include neurological dysfunction, skeletal dysplasias, reduced fecundity and reproduction, and cardiovascular pathologies. Collectively, this review provides reference information for genetic investigations of perturbed mammalian sulfate biology.

关 键 词：SULFATE Pathogenetics Transport SULFOTRANSFERASE SULFATASE PAPS 

分 类 号：Q95[生物学—动物学]