Genetics and pathophysiology of mammalian sulfate biology

J Genet Genomics. 2017 Jan 20;44(1):7-20. doi: 10.1016/j.jgg.2016.08.001. Epub 2016 Aug 13.

Abstract

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.

Keywords: PAPS; Pathogenetics; Sulfatase; Sulfate; Sulfotransferase; Transport.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzymes / genetics
  • Enzymes / metabolism
  • Genetic Phenomena*
  • Homeostasis / genetics
  • Humans
  • Pharmaceutical Preparations / metabolism
  • Phenotype
  • Sulfates / metabolism*

Substances

  • Enzymes
  • Pharmaceutical Preparations
  • Sulfates