Insulin glutathione reductase

There is a correlation between the backbone conformations which commonly flank disulfides and the frequency with which disulfides occur in the different types of overall protein structure (see Section III,A for explanation of structure types), although it is unclear which preference is the cause and which the effect. There are very few disulfides in the antiparallel helical bundle proteins and none in proteins based on pure parallel /3 sheet (except for active-site disulfides such as in glutathione reductase). Antiparallel /3 sheet, mixed /8 sheet, and the miscellaneous a proteins have a half-cystine content of 0-5%. Small proteins with low secondary-structure content often have up to 15-20% half-cystine. Figure 52 shows the structure of insulin, one of the small proteins in which disulfides appear to play a major role in the organization and stability of the overall structure. 

This enzyme [EC 1.8.4.2], also known as glutathione insulin transhydrogenase and insulin reductase, catalyzes the reaction of two glutathione with a disulfide bond in a protein to produce glutathione disulfide and a protein with two new thiol groups. The enzyme can reduce insulin and a number of other proteins. 

Glutathione helps to maintain the sulfhydryl groups of proteins in a reduced state. An enzyme, protein-disulfide reductase, catalyzes sulfhydryl disulfide interchanges between glutathione and proteins. The reductase is important in insulin breakdown and may catalyze the reassortment of disulfide bonds during polypeptide chain folding. 

The thioredoxin system, consisting of thioredoxin and thioredoxin reductase, was originally discovered as the hydrogen carrier system, which provides, with NADPH, the reducing potential for the reduction of ribonucleotides (5, 35). Since then considerable evidence has been accumulated to indicate that this or a closely related system also participates in a variety of other enzymatic reductions. For instance thioredoxin can function as an electron carrier between NADPH and several disulfides, such as insulin, lipoate and oxidized glutathione. Furthermore Porque et al. (114) have shown that thioredoxin and thioredoxin reductase from yeast can function as hydrogen carriers in the reduction of methionine sulfoxide and sulfate. 

Protein-disulfide reductase (glutathione) [ glutathione protein-disulfide oxidoreductase EC 1.8.4.2) has been reported in hepatic tissue (52). The enzyme rapidly cleaved the three disulfide bonds of insulin and the disulfide bonds of other proteins. The Km for reduced glutathione was 8.9 X 10 3M, a very high value. The enzyme catalyzed the reaction (Equation 3) from either direction. 

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