Enzyme biological activity, sulfhydryl groups

Disulfides. As shown in Figure 4, the and h-chains of insulin are connected by two disulfide bridges and there is an intrachain cycHc disulfide link on the -chain (see Insulin and other antidiabetic drugs). Vasopressin [9034-50-8] and oxytocin [50-56-6] also contain disulfide links (48). Oxidation of thiols to disulfides and reduction of the latter back to thiols are quite common and important in biological systems, eg, cysteine to cystine or reduced Hpoic acid to oxidized Hpoic acid. Many enzymes depend on free SH groups for activation—deactivation reactions. The oxidation—reduction of glutathione (Glu-Cys-Gly) depends on the sulfhydryl group from cysteine. 

Ribonucleotide reductase is notable in that its reaction mechanism provides the best-characterized example of the involvement of free radicals in biochemical transformations, once thought to be rare in biological systems. The enzyme in E. coli and most eukaryotes is a dimer, with subunits designated R1 and R2 (Fig. 22-40). The R1 subunit contains two lands of regulatory sites, as described below. The two active sites of the enzyme are formed at the interface between the R1 and R2 subunits. At each active site, R1 contributes two sulfhydryl groups required for activity and R2 contributes a stable tyrosyl radical. The R2 subunit also has a binuclear iron (Fe3+) cofactor that helps generate and stabilize the tyrosyl radicals (Fig. 22-40). The tyrosyl radical is too far from the active site to interact directly with the site, but it generates another radical at the active site that functions in catalysis. 

Like cadmium, mercury(II) has a strong affinity for sulfhydryl groups in proteins, enzymes, hemoglobin, and serum albumin. Because of the abundance of sulfhydryl groups in active sites of many enzymes, it is difficult to establish exactly which enzymes are affected by mercury in biological systems. 

Some biological effects may be mediated by reaction of the epoxy groups of trichothecenes with sulfhydryl groups on enzymes and binding of certain trichothecenes to membrane components. T-2 toxin rapidly affected glucose, nucleotide and amino acid transporters as well as calcium/ potassium channel activities in vitro indicating alteration of cell membrane functions independent of protein synthesis inhibition (Brunner and Morris, 1988). In pigs, DAS was... 

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