L-cysteine sulfoxide

Nishimura and coworkers57-59 studied the y-radiolysis of aqueous solutions of sulfoxide amino acids. Sulfoxide amino acids are the precursors of the flavors of onions (S-propyl-L-cysteine sulfoxide, S-methyl-L-cysteine sulfoxide and S-(l-propenyl)-L-cysteine sulfoxide) and garlic (S-allyl-L-cysteine sulfoxide). In studies on sprout inhibition of onion by /-irradiation it was found that the characteristic flavor of onions became milder. In the y-radiolysis of an aqueous solution of S-propyl-L-cysteine sulfoxide (PCSO)57,58 they identified as the main products alanine, cysteic acid, dipropyl disulfide and dipropyl sulfide. In the radiolysis of S-allyl-L-cysteine sulfoxide (ACSO) they found that the main products are S-allyl-L-cysteine, cysteic acid, cystine, allyl alcohol, propyl allyl sulfide and diallyl sulfide. The mechanisms of formation of the products were partly elucidated by the study of the radiolysis in the presence of N20 and Br- as eaq - and OH radicals scavengers, respectively. 

FIGURE 7. The reactions of OH radical with alkyl-L-cysteine sulfoxide. 

For DMS and DMTS, S-mothyl-L-cysteine sulfoxide is a precursor action of a C-S lyase enzyme yields methanesulfenic acid, CH3-S-OH, and hence methyl methanethiosulfinate, CH3-SO-S-CH3. Disproportionation reactions yield polysulfides such as DMS.56... 

Methyl L-cysteine sulfoxide 5 Chem. Ind. (London) I9S6,1428 Acta Oystallogr. 1962,15. 635... 

Onions Allium cepa) were shown to contain similar compounds, S-methyl and S-propyl-L-cysteine sulfoxide (20). The principal flavor precursor in onion is fmn -S( + )-l-propenyl-L-cysteine sulfoxide 21, 22, 23). It is responsible for the lachrymatory properties and bitter taste of freshly cut onion (22). All these compounds were cleaved by an S-alkyl-L-cysteine sulfoxide lyase from onion 24, 25) which yielded pyruvate and ammonia in addition to a sulfur compound. The enzyme has also been demonstrated in Bacillus subtilis 26) and in a number of the Cruciferae where the only substrate known is S-methyl-L-cysteine sulfoxide (27). The product presumably gives rise to dimethyl disulfide which is the odor of cooked cabbage. 

Characteristics of the Enzyme. S-alkyl-L-cysteine sulfoxide lyases prepared from garlic 17, 19) and onion 24, 25, 39) are similar. They differ primarily in their response to pH—the garlic enzyme has a broad pH optimum from 5 to 8 and may be precipitated at pH 4.0 and redissolved without loss of activity (17) while the onion enzyme is sensitive to acid and is most active at pH 8.8 in pyrophosphate buffer 24, 39). The purified garlic enzyme showed a sharper pH optimum at pH 6.5 40). The Brassica enzyme is most active at pH 8.5 in borate buffer (27) and remains soluble and active when other proteins are precipitated at pH 4.0. 

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). 

Figure 1 Metabolism of DCVC and mechanism of nephrotoxicity. O S-, 2-dichlorovinyl)-L-cysteine S-(1,2-dichlorovinyl)-A/-acetyl-L-cysteine the a-keto acid metabolite of S-(1,2-dichlorovinyl)-L-cysteine O S-(1,2-dichlorovinyl)-L-cysteine sulfoxide 1,2-dichlorovin-ylthiol S-[1-chloro-2-(S-glutathionyl)vinyl]-L-cysteine sulfoxide.

Garlic is also a medicinal used by the Kallawaya herbalists, and it is mentioned that crushed garlic contains the powerful bactericidal agent allyl allylthiosulfinate (allicin), which is formed by the interaction of the enzyme allinase with the substrate 5-ethyl L-cystein sulfoxide (Bastien, 1987, p. 102, n. 6). Bastien in turn supplies the results of an experiment on mice. Thus, in miee infected with sarcoma, injection either of the enzyme allinase or the substrate 5-ethyl L-cystein sulfoxide (alliin) alone had no effect, all animals dying within 16 days. However, in infected mice treated with both the enzyme and the substrate, the animals were still alive after 6 months. Allicin is therefore the active anticancer ingredient, as will be emphasized especially in Chapter 5. 

Ostermayer, F. and Tarbell, D., 1959. Products of acidic hydrolysis of S-methyl-L-cysteine sulfoxide the isolation of methylmethane-thiosulfonate and mechanism of hydrolysis. J. Am. Chem. Soc., 82 3752—3755. 

McCySO S-metliyl-l cysteine sulfoxide MeCySO IG S-mcthyhL-cysteine sulfoxide + glucose nd not detected... 

The primary sulfur-containing constituents in garlic bulbs are y-glutamyl-S-alk(en)yl-L-cysteines and S-alk(en)yl-L-cysteine sulfoxides. The content of 5alk(en)ylcysteine... 

Methylcysteine sulfoxide accumulates in certain plants of the Cruciferae and Liliaceae (Thompson, 1967), but could not be detected in several legumes or plants of six other families examined (Fujiwaraet ai, 1958). The compound has been isolated exclusively as (-t-XS-methyl-L-cysteine sulfoxide, suggesting that it is not formed as an artifact by chemical oxidation of 5-methylcysteine. 

Reaction 8, the direct cleavage of L-cystine to produce pyruvate and thiocysteine has been studied in much more detail. An enzyme has been found in a number of Brassica species which cattdyzes the production of pyruvate from L-cystine (Mazelis et al., 1%7). The specificity of this enzyme using six-fold purified B. napobrassica root preparations was limited to L-cystine and 5-methyl-L-cysteine sulfoxide of naturally occurring substrates. The enzyme was completely dependent on added pyridoxal 5 -phosphate. The for L-cystine was 1 vaM and 0.5 pM for pyridoxal phosphate. L-Cysteine was not a substrate but was a competitive inhibitor at low concentrations. This was due to the -SH function since glutathione had the same effect. The Aj for these compounds was 0.15 mM. 

Lash, L.H., Putt, D.A., Hueni, S.E., Krause, R.J., and Elfarra, A.A. (2003) Roles of necrosis, apoptosis, and mitochondrial dysfunction in S-(l,2-dichlorovinyl)-L-cysteine sulfoxide-induced cytotoxicity in primary cultures of human renal proximal tubular cells. J. Pharmacol. Exp. Ther. 305, 1163-1172. 

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