Interaction of insulin analogs, glucagon, growth hormone, vasopressin, oxytocin, and scrambled forms of ribonuclease and lysozyme with glytathione-insulin transhydrogenase (thiol: protein-disulfide oxidoreductase): dependence upon conformation.
Interactions of several proteins with glutathione-insulin transhydrogenase (GIT) have been investigated by determining their ability to inhibit degradation of 125I-labeled insulin catalyzed by GIT. The inhibition by every insulin analog (des-Asn-des-Ala-pork insulin, desoctapeptide-pork insulin, des-Ala-pork insulin, pork insulin, proinsulin, and guinea pig insulin) was competitive vs. competitive vs. insulin indicating that they function as alternate substrates. The insulin analogs with the least hormonal activity showed the highest potency as inhigitors of insulin degradation. Whereas native ribonuclease and lysozyme showed little or no inhibition, their scrambled forms (i.e. reduced and randomly reoxidized) showed competitive inhibition with a potency greater than that of insulin. These results suggest that the conformation of the substrate or inhibitor is probably the major factor in determining the specificity for (or binding to) the enzyme. Studies withother peptide hormones showed competitive inhibition with vasopressin and oxytocin and noncompetitive inhibition with glycagon. The inhibition with growth hormone could be either competitive or noncompetitive. The inhibition by glucagon and growth hormone (physiologic antagonists of insulin) could serve as a control mechanism to modulate the activity of enzyme. The following showed very little or no inhibition; the native and scrambled form of pepsinogen, trypsin inhibitor of beef pancreas and of lima bean, C-peptide of pork proinsulin, and heptapeptide (B23-B29) of insulin.
D000818:Animals; D002417:Cattle; D005934:Glucagon; D013006:Growth Hormone; D006168:Guinea Pigs; D007328:Insulin / Q000031:analogs & derivatives*; D007700:Kinetics; D008433:Mathematics; D009113:Muramidase; D010088:Oxidoreductases / Q000378:metabolism*; D010121:Oxytocin; D010179:Pancreas / Q000201:enzymology; D011487:Protein Conformation; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism*; D012260:Ribonucleases; D013329:Structure-Activity Relationship; D013552:Swine; D014667:Vasopressins
D007328:Insulin; D014667:Vasopressins; D010121:Oxytocin; D013006:Growth Hormone; D005934:Glucagon; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D012260:Ribonucleases; D009113:Muramidase