Cystine disulfoxide

Cystine and cysteine also can be oxidized under the same conditions but the analytical methods to detect these oxidation products in proteins have not been developed yet. The different oxidation products of cystine, which have been synthesized (55-58), are cystine disulfoxide (NH2-CH-(COOH)-CH2-SO-SO-CH2-(COOH)-CH-NH2), cystine disul-fone (NH2-CH- (COOH) -CH2-C02-S02-CH2-( COOH )-CH-NH2), cysteine sulfenic acid (NH2-CH-(COOH)-CH2-SOH), cysteine sul-finic acid (NH2-CH-(C00H)-CH2-S02H), and cysteine sulfonic acid or cysteic acid (NH2-CH-(C00H)-CH2-S03H). It is doubtful that all of these derivatives described in 1935 by Bennett are present in proteins. 

Oxidation of Cystine, Cystine has been reported to initiate a series of reactions in which the S—S bond remains intact. An oxidation product is cystine disulfoxide, RSOSOR. This compound can yield both cysteine and sulfate in the intact rat, but most of it is converted to taurine. Both carboxyl groups of cystine disulfoxide are removed by a decarboxylase different from cysteic decarboxylase. Oxidation and hydrolysis of the decarboxylation product would yield two equivalents of taurine, but the individual steps of this conversion have not been isolated. 

Feeding experiments indicate that the oxidation to sulfate and excretion in the urine decreases as follows for the compounds listed cysteine > cystine > cystine disulfoxide > cysteinesulfinic acid > cysteic acid. The above scheme shows that cystine and cysteine are both oxidized to sulfate, but it seems quite logical to expect that the oxidation of cystine is initiated by its first being cleaved to cysteine. 

Another metabolic pathway directly from cystine which yields taurine has been proposed by Medes and co-workers. The steps involved are given in reactions 9 to 12 of Fig. 2. The initial oxidation product, cystine disulfoxide, is readily oxidized to sulfate in the animal organism. The oxidation step from cystine to the disulfoxide appears to be reversible, as Bennett found that this compound was capable of replacing cystine in the diet of the rat in equimolar amounts. Decarboxylation of cystine disulfoxide was deduced from the active decarboxylation of cystine with the simultaneous absorption of O2 by an enzyme present in liver brei. 

Tests to determine the nature of the compounds formed from the decarboxylation of cystine that could undergo oxidation led to the observation that cystamine disulfoxide was oxidized with ease, whereas cystamine was completely resistant. From these observations, it was hypothesized that two oxidizing enzymes may be involved in the reaction, one oxidizing cystine to the disulfoxide, and one continuing the oxidation of the cystamine disulfoxide subsequent to the decarboxylation of the cystine disulfoxide. If it is assumed that the cystamine disulfoxide is simultaneously oxidized and cleaved to 2-aminoethanesulfinic acid, the oxidation scheme leads to the intermediate that was established for the biosynthesis of taurine from cysteine by Awapara. ... 

Cys Ethyl arachidonate Cystine, H2S, cysteic acid, alanine, cystine-disulfoxide... 

This amine is apparently not formed by a direct decarboxylation of cysteine. An enzymic decarboxylation and reduction of cystine disulfoxide, a potential precursor of cysteamine [Eq. (4)], is only a hypothetical pathway at present. The pantetheine moiety of coenzyme A may, however, yield cysteamine in vivo ( 8). Cysteamine in vivo and in vitro is partly transformed to hypotaurine ( 9) and its S appears as SOr in the urine. An interesting property of this amine is its powerful protecting action in vivo against lethal doses of X-rays. 

In addition, Medes and Floyd (86) have presented evidence that in the liver of rats two enzyme systems exist which bring about the oxidation of cystine. One of them is cysteine oxidase B, which was described on page 388, and which acts likewise on cystine to form cysteic acid the rate of this oxidation is slightly less than the corresponding oxidation of cysteine. The other is a cysteine oxidase which results in the formation of cystine disulfoxide, RSOSOR. Greenstein and Leuthardt (55) have studied the distribution of cystine oxidase in the different organs of mice. Only liver, kidney, and pancreas, in order of decreasing activity, contain this enzyme. On the other hand, no noticeable activity of cystine oxidase has been revealed in tumors in the same animals. 

The metabolism of cystine disulfoxide itself has been the object of a number of investigations. According to Medes (84), ingestion of cystine disulfoxide in man is followed by a considerable increase in urinary sulfate. Two theories have been presented to explain the formation of sulfate from cystine disulfoxide. The first one assumes that, prior to oxidation to sulfate, cystine disulfoxide is reduced in the organism to cystine. This theory... 

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