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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
DOI: 10.1097/MED.0b013e3283202555
Type: Journal Article
Subjects: Animals
Gastrin-Releasing Peptide.physiology
Gastrointestinal Diseases.enzymology.genetics.physiopathology
Gastrointestinal Hormones.physiology
Mice, Knockout
Models, Animal
Proprotein Convertases.physiology
Protein Precursors.physiology
Appears in Collections:Journal articles

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