The biological properties of insulins with tyrosine replaced by phenylalanine at positions 14 and 19 of the A chain.
The tyrosine residues at positions 14 and 19 of the insulin A chain are of both theoretical and practical interest. In order to clarify their roles in insulin function we have studied the biological properties of the two chemically modified insulins in which phenylalanine replaces tyrosine at these sites. In comparison to native bovine insulin the lipogenesis potency (in rat adipocytes) of pheA19-insulin was 33% and of pheA14-insulin was 84%. Metabolic clearance rates (MCR) over a range of plasma concentrations were also reduced compared to native insulin both with pheA19-insulin and pheA14-insulin. Plasma half-disappearance times were 4.6 min for insulin, 5.1 min for pheA14-insulin and 7.3 min for pheA19-insulin. However, as a result of these differences in metabolism, the in vivo hypoglycaemic activity of the modified insulins was not reduced. Both modified insulins conform to the general relationship between lipogenesis potency and MCR. These results confirm the importance of the A19 tyrosine to the activity of insulin and show that manipulation at the A14 position can also influence activity even though this residue is not thought to be directly involved in receptor binding.
D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats
D007328:Insulin; D008055:Lipids; C027603:insulin, Phe(A14)-; C027602:insulin, Phe(A19)-