Cysteinesulfinic acid

All these enzymes have similar specificity and require the L-cysteine sulfoxide portion of the molecule. S-alkyl cysteines are not substrates 18, 24, 27, 39) neither are sulfoxides of N-substituted L-cysteine, / -di-methyl-L-cysteine, y8-thiopropionic acid 18), D-cysteine 19), and dl-methionine 18, 24, 39), nor do the enzymes act on L-cysteine itself 24, 27, 39), cysteic acid, cysteinesulfinic acid 24, 27), or cycloalliin 24, 39). There may be some action on S-ethylcysteine sulfone (42). 

Sulfinic acids probably have the structure (1) rather than (2), and certainly any equilibrium between (1) and (2) lies on the side of the hydroxy isomer (1) (Figure l).la The free sulfinic acids are rather unstable and tend to disproportionate into the thiolsulfonate and the sulfinic acid hence, they are generally used as the stable sodium salts. Owing to their instability, few sulfinic acids occur naturally, but they may exist as intermediates in the oxidation of thiols thus, cysteinesulfinic acid is an intermediate in the oxidation of cysteine and 2-aminoethanesulfinic acid has been isolated from molluscs. 

The reactions of cystine with base are more complicated and not completely elucidated. Among products identified are cysteine, cysteinesulfinic acid, 5-sulfocysteine, cysteic acid, acetic acid, thiosulfate, and the persulfide H02CCH(NH2)CH2-S-SH (DeMarcoeta/., 1%3 Danehy and Hunter, 1%7). Disulfide interchange (see Section II1,C) can also take place in base (Ryle and Sanger, 1955). 

The use of an amine donor, which forms an unstable keto coproduct. For instance, cysteinesulfinic acid was used in transamination to furnish the p-sulfinic acid analog of pyruvate, which spontaneously decomposes into SO2 and pymvate [1732]. In a related fashion, a,co-diamino acids, such as ornithine or leucine yield amino-ketoacids, which (nonenzymatically) cyclize to the corresponding A -pyrroline-5-carboxylate and A -piperidine-2-carboxylate, respectively, as dead-end products [1733, 1734],... 

Cysteinesulfinic Acid. Cysteine is oxidized by enzyme systems present in bacteria and in liver to the corresponding sulfinic acid. It has been suggested that the unstable sulfenic acid is an intermediate in this oxidation. The nature of the reaction that produces cysteinesulfinic acid is not known. The subsequent metabolism of the sulfinic acid may proceed by any of three pathways. One involves further oxidation to cysteine-sulfonic acid, cysteic acid. The enzyme responsible has not been separated from the system responsible for the formation of cysteinesulfinic acid. Cysteinesulfonic acid is decarboxylated to taurine (I) by the decarboxylase mentioned previously (p. 284). 

A second pathway of cysteinesulfinic acid involves decarboxylation to hypotaurine (II). This reaction is followed by oxidation to taurine. This pathway appears to be more important than the cysteic acid pathway. 

The major portion of cysteinesulfinic acid appears to be metabolized... 

Synthesis of Sulfur Amino Acids. Of the many oxidation states of sulfur, only sulfite has been shown to be utilized by cell-free systems in the net synthesis of compounds with carbon-sulfur bonds, although mutant studies have indicated that more reduced forms can be incorporated. The formation of cysteinesulfinic acid from sulfite has been demonstrated in extracts of acetone-dried rabbit kidney it is possible that this reaction participates in the principal mechanism of sulfur incorporation. In many organisms that require preformed sulfur amino acids, cysteine may be formed from methionine. Only the sulfur of methionine is transferred to cysteine the carbon skeleton of cysteine is derived exclusively from serine. Transsulfuration appears to require the formation of homocysteine from methionine. Homocysteine and serine condense to form a thioether, cystathionine (V). Pyridoxal phosphate has been... 

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. 

The first well-established product of the oxidation of cysteine is cysteinesulfinic acid. This compound has been isolated by a number of investigators, and its subsequent reactions fall in line well with the properties expected of an intermediate in the metabolism of cysteine. 

No convincing evidence is available at present for the formation of cysteinesulfenic acid by either hydrolysis or oxidation in biological systems. If the sulfenic acid is formed, it is unstable under physiological conditions and undergoes spontaneous dismutation into cysteine and cysteinesulfinic acid, according to equation 3 (see reaction 3, Fig. 2). 

The position of cysteinesulfinic acid as the key intermediate in the oxidation of cysteine rests largely on the ease of its conversion to a number of products associated with the metabolism of cysteine sulfur and on its complete oxidation to sulfate. As previously pointed out, in feeding experiments cysteinesulfinic acid was readily oxidized to sulfate in the... 

Extracts of P. vulgaris contained a cysteinesulfinic acid transaminase which, in the presence of a-ketoglutarate, converts the sulfinate to /3-sulfinylpyruvic acid. The sulfinylpyruvate, in turn, is desulfinated to pyruvate and SOs (reaction 5). The SO3" is then oxidized to S04 (reaction 6). 

The other enzyme catalyzes a reaction characteristic of animal tissues, and not found in P. vulgaris, namely, the oxidative deamination of cys-teine-sulfinate to jS-sulfinylpyruvate and NHj. This enzyme has been named cysteinesulfinic acid dehydrogenase II, and it appears to be DPN-dependent. j8-Sulfinylpymvate does not accumulate in the reaction because of its rapid oxidation to jS-sulfonylpyruvate. The over-all reaction is represented in equation 3a. 

The scheme of oxidation of cysteinesulfinic acid given in Fig. 2 fits in with the observations that its oxidation yields alanine. This, of course, could readily be derived from pyruvate by transamination. 

An alternate and competing pathway for the metabolism of cysteinesulfinic acid is its oxidation to cysteic acid (reaction 7, Fig. 2). A new enzyme, L-cysteinesulfinate dehydrogenase, has been isolated from P. vulgaris which catalyzes this reaction. Its unique property is that it is reported to require a hitherto unknown coenzyme, designated as Co III, for activity. A good source of Co III is boiled yeast extract. The reduced form of the coenzyme has an absorption spectrum characteristic of dehydropyridine nucleotides. The structure of this supposed new coenzyme is uncertain. The fact that it can substitute for DPN in many reactions supposedly specific for the latter leads to some wonderment. 

Werle and Pechmann 184) have presented evidence that diamine oxidase from plants could be activated by pyridoxal. The rate of inhibition of enzyme systems by isonicotinic acid hydrazide has been used as a means of detecting the presence of pyridoxal phosphate as a coenzyme, particularly when it is tightly bound to the apoenzyme 205, 206). Davison 166) has shown that the rates of inhibition of an established pyridoxal phosphate containing enzyme, cysteinesulfinic acid decarboxylase 207, 208), and diamine oxidase are similar and that pyridoxal phosphate will reactivate diamine oxidase after inhibition with isonicotinic acid hydrazide. On this basis it has been suggested that pyridoxal phosphate is probably involved as a coenzyme for diamine oxidase. 

It is known from in vivo experiments that cysteinesulfinic acid (10) taurine, and hypotaurine (11-13) are intermediate products in the metabolic pathway of cysteine. The pathway between cysteine and cysteinesulfinic acid has not been clarified, although a hypothetical mechanism, based on chemical considerations (14,16) is available ... 

In animal tissues cysteinesulfinic acid can undergo transamination, decarboxylation, and oxidation. In certain strains of Proteus vulgaris an alternative oxidation and transamination operate simultaneously 18). It was shown by Cohen 19) and by Kearney and Singer 18) that both in animal and microbial systems the transamination of cysteine sulfinate catalyzed by glutamate-aspartate transaminase proceeds as follows ... 

The finding of a dietary requirement for taurine in the human infant is consistent with the negligible activity of cysteinesulfinic acid decarboxylase present both in fetal and in mature human liver (Gaull et al., 1977). 

The cysteinesulfinic acid(CSA)pathway has been till now considered the most important route for taurine production in animal tissues.However this claim needs some criticism for the following reasons ... 

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