Mutant Human Insulins and Insulin Structure-Function Relationships
Studies based on heritable defects in human function (sometimes called inborn errors of metabolism) have long played an important role to increase our understanding of mammalian biology in areas as diverse as biochemistry, cell and organismal physiology, and clinical medicine. In fact, studies over very many years of the hemoglobinopathies have formed a paradigm for the analysis of changes in molecular structure which both arise from genetic mutation and lead to important physiological consequences. Early work in the general area emphasized, for technical reasons alone, the results of mutations leading to: (a) structural change in the most abundant blood proteins; and (b) the replacement of amino acid residues that would change the properties of those proteins with respect to charge and electrophoretic mobility. Exceptions (including those involving important intracellular enzymes) are easily identified, but analysis of human tissues for genetic changes that result in concomitantly changed protein structure remained difficult for an extended period. Recent technical and methodological advances (including high performance liquid chromatography, instrumentation for ultramicro protein analysis, and the vast approaches of recombinant DNA analysis), however, have instilled renewed ability and interest to the field. The benefits that afford the study of genetic mutation in humans and of corresponding abnormal proteins are clear. They include determination of the genetic causes and implications of human disease and the importance of detailed protein structure in the attainment of correct protein, cellular, and organismal function. In many ways the analysis of human gene mutations helps to identify genes, proteins, and protein domains of special importance to normal and abnormal mammalian physiology.
KeywordsHuman Insulin Insulin Analog Insulin Gene Amino Acid Replacement Abnormal Insulin
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