title: Degradation of the four monoiodoinsulin isomers by the insulin protease of rat liver.
abstract: The cleavage of insulin by the partially purified insulin protease was studied using the four [125I]tyrosine-monoiodoinsulins (tyrosine A-14 and A-19 of the A-chain; tyrosine B-16 and B-26 of the B-chain). The rates of conversion of the four isomers to trichloroacetic acid-soluble form was in the order B-26 greater than A-14 greater than A-19 greater than B-16. The following was observed in experiments which gave 19/14/5/3 percent conversion to trichloroacetic acid-soluble products: the loss of ability to bind to IM-9 lymphocytes was approx. 55% for all four isomers. About 70% of the radioactivity was in the 'insulin' peak, and about 30% was in peptides smaller than insulin as judged by gel filtration on Sephadex G-50. The descending limb of the 'insulin' peak contained significant amounts of radioactive material not binding to IM-9 lymphocytes. This material showed multiple peaks when applied to high performance liquid chromatography. Other experiments were designed to cause an almost complete degradation of the isomers. Under these conditions, the radioactivity eluted on Sephadex G-50 largely as iodotyrosine (and some small peptides) using the A-14, B-16 and B-26 isomers, whereas iodotyrosine was absent using the A-19 isomer. Thus, the insulin protease appears to first degrade insulin to multiple products with molecular sizes slightly smaller than insulin and subsequently to small peptides (e.g containing tyrosine A-19) and amino acids (e.g. tyrosine A-14, B-16 and B-26).
mesh_terms: D000818:Animals; D006868:Hydrolysis; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism; D007339:Insulysin / Q000378:metabolism*; D007536:Isomerism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D007328:Insulin; C008147:insulin, iodo-; D011972:Receptor, Insulin; D010447:Peptide Hydrolases; D007339:Insulysin