Glutathione oxidation-reduction

While we can thus correlate the facts in the form of a mechanism, it is, as written, a perpetual-motion mechanism. Obviously, an additional factor has to be introduced to account for the fact that the protein-glutathione oxidation reduction first goes in one direction, then in the reverse. Various possibilities present themselves, but none has sufficient factual basis to merit discussion here. 

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. 

Perhaps this may be considered in relation to the suggestion of Kellermeyer et al. (K5) that the drugs involved are transformed in vivo to redox intermediates. Furthermore, the reducing capacity of RBC was shown to be a function of GSH content. Reduction of this capacity by intravenous infusion of sodium thiosulfate solution reflects changes in the intracellular oxidation-reduction system of glutathione, the oxidized form being favored (Cl, S9). 

A major class of enzymes that catalyze oxidation-reduction reactions. This class includes dehydrogenases, reductases, oxygenases, peroxidases, and a few synthases. Examples include alcohol dehydrogenase (EC 1.1.1.1), aldehyde oxidase (EC 1.2.3.1), orotate reductase (EC 1.3.1.14), glutamate synthase (EC 1.4.1.14), NAD(P) transhydrogenase (EC 1.6.1.1), and glutathione peroxidase (EC 1.11.1.9). 

If there are three or more -SH groups in a chain some incorrect pairing may, and often does, occur. Tire protein disulfide isomerases break these bonds and allow new ones to form.92 The active sites of these isomerases contain pairs of -SH groups which can be oxidized to internal -S-S- bridges by NAD+-dependent enzymes. These enzymes and their relatives thioredoxin and glutaredoxin are discussed further in Box 15-C. Glutathione and oxidation-reduction buffering are considered in Box 11-B. 

BOX 11-B GLUTATHIONE, INTRACELLULAR OXIDATION-REDUCTION BUFFER (continued)... 

Anomalous response to the NADH oxidase in animal cells, such as amiloride-insensitive proton transport, may be based on activation of the H+-ATPase or direct electron transport-linked proton transfer. Further definition of the components of the NADH oxidase and the characteristics of electron transport are needed. In addition, the presence of a poorly characterized glutathione oxidase in the plasma membrane opens an alternative for oxidation-reduction control of proton transport. At this stage no evidence has been found for control of HCOj/Cl" exchange or organic acid transport by the plasma membrane oxidase. 

Many, but not all, proteins are sensitive to alterations in the oxidation-reduction potential of their environment. The effect is caused in part by oxidation of sulfhydryl groups or reduction of disulfide bonds. Not all proteins are equally sensitive to such alterations, but when they are, it is critical to be aware of their sensitivity. The purification or assay of some proteins can be accomplished only by providing reducing conditions (reduced glutathione, free cysteine, dithiothreitol, or mercap-toethanol) in all buffer solutions. 

Glutathione (Peptide Institute Inc., Japan) was used as the acidic peptide in this experimental work. It has important role in biochemical oxidation/reduction reaction. The structure is shown in Fig.l. 

Two CoA-containing nucleotides which inhibit DNA-dependent RNA polymerase have recently been isolated from E. coli and other organisms. One consists of CoA and glutathione joined by a disulphide bridge the other is a CoA dimer plus two equivalents of glutamic acid. The inhibition of the polymerase by these nucleotides is not due to an oxidation-reduction reaction but appears to involve their binding to the DNA-RNA polymerase complex. ... 

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