Insulin disulphide bonds reactivity

Acylation, with phenyl isocyanate, has the same effect of iodination and methylation, one interchain bond becoming unreactive towards the sulphite at pH 7 On the contrary, extensive acetylation and succinylation or removal of the C-terminal residues (DAA insulin) have no apparent effect on the disulphide bonds reactivity as proven by the fact that the corresponding insulin derivatives are split by the sulphite into the constituent chains. 

When these results are viewed in terms of the hormonal activity of the substituted insulins, an interesting parallelism is noted between the effects of the substitutions on disulphide bonds reactivity and on the biological activity the disulphide bonds reactivity appears to be affected only by those substitutions which are known to abolish the biological activity of the hormone, when carried beyond a certain level. It was therefore planned to study the changes of biological activity and of -S-S- bonds reactivity as a function of the degree of substitution. This aspect was studied in detail on iodinated and methylated insulins. 

YHiile the fractional catabolic rate of low iodina-ted insulin is about 4-6, that of high iodinated is of the order of 2fo fully methylated or acylated insulins are degraded at the same rate of about 2 fof-m.n. (16).The peculiarity of these results lays in the fact that de-gradative processes, such as excessive iodination, usually lead to an increase in rate of catabolism of the proteins for instance, this behaviour is constantly observed in the case of plasma proteins. Hlfhen the separated chains at different level of iodine substitution, either in the reduced or in the fully sulphonated form, were studied in man their rate of catabolism was found to be of the same order of that of native insulin. On the other hand DAA insulin is degraded at a rate of the same order of that of native insulin. It may be worth to note that DAA insulin is biologically inactive, but its disulphide bonds are fully reactive. 

Some aspects of our results can be discussed in the light of the pecualiar position that insulin occupies among the proteins, as far as the reactivity of its -S-S- bonds is concerned. In most native proteins the disulphide bonds are relatively unreactive towards the sulphite and thiols at pH 7 (4 14). 

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