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Title: | Peptide processing and biology in human disease. | Austin Authors: | Kovac, Suzana;Shulkes, Arthur;Baldwin, Graham S | Affiliation: | University of Melbourne, Department of Surgery, Austin Health, Heidelberg, Victoria, Australia | Issue Date: | 1-Feb-2009 | Publication information: | Current Opinion in Endocrinology, Diabetes, and Obesity; 16(1): 79-85 | Abstract: | To describe recent advances in the processing of gastrointestinal hormones, and the consequences for human disease of mutations in the enzymes involved.Although gastrointestinal prohormones were long regarded as devoid of biological activity, recent data indicate that the prohormones for both gastrin and gastrin-releasing peptide are bioactive, through different receptors from the mature hormones. Mutations in the family of prohormone convertases responsible for the initial steps in the processing of gastrointestinal hormones are associated with several different pathophysiological conditions in humans.Human mutational studies, when taken together with the phenotypes observed in mice deficient in the prohormone convertases, emphasize the crucial importance of the processing enzymes in mammalian biology. Although the phenotypes may often be ascribed to defective production of a mature hormone or growth factor, the recognition that the precursors are independently bioactive suggests that the increased precursor concentrations may also contribute to the symptoms. The observation that the precursors often act through different receptors from the mature hormones may permit the development of precursor-selective antagonists for therapeutic use. | Gov't Doc #: | 19104240 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/10735 | DOI: | 10.1097/MED.0b013e3283202555 | Journal: | Current opinion in endocrinology, diabetes, and obesity | URL: | https://pubmed.ncbi.nlm.nih.gov/19104240 | Type: | Journal Article | Subjects: | Animals Furin.genetics.physiology Gastrin-Releasing Peptide.physiology Gastrins.physiology Gastrointestinal Diseases.enzymology.genetics.physiopathology Gastrointestinal Hormones.physiology Hormones.physiology Humans Mice Mice, Knockout Models, Animal Mutation Peptides.genetics.metabolism.physiology Proprotein Convertases.physiology Protein Precursors.physiology |
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