Mechanisms of cysteine

Scheme 2 Mechanism of cysteine protease inactivation via AOMK probes...

The catalytic mechanism of cysteine proteinases is broadly similar to that of serine proteinases, in that there is an acyl-enzyme intermediate (Fersht, 1985, p. 414) and a histidine residue which is considered to act as a general acid-base catalyst however the balance of evidence appears to favour the mechanism shown in Scheme 18 in which, in contrast to that for the serine... 

The catalytic mechanism of cysteine proteinases. The pathway to the acyl-enzyme is shown its hydrolysis probably involves general base catalysed attack of water in the near microscopic reverse of the above mechanism. Only one proton is in flight during deacylation (Szawelski and Wharton, 1981)... 

Albeck, A. and Kliper, S., Mechanism of cysteine protease inactivation by peptidyl epoxides, Biochem. J. 322, 879-884, 1997. 

Figure 6. Mechanism of cysteine-fatty acid adduct formation from the reaction of 13-hydroperoxylinoleic acid and cysteine in the absence of O2. The epoxyallylic radical at the top originates from the oxydiene radical of 13-hydroperoxylinoleic acid abbreviated structure) and RS is the cysteine thiyl radical. Reproduced with permission from Ref. 28.)...

Scheme 8. Mechanism of cysteine protease (CP) inhibition by Ru-pac complexes. Published in RSC Journal (taken from Ref. (28)).

Interestingly, rrO- PAH/Co TsPc 3 electrode in 0.1 mol PBS catalyzed oxidation of cysteine to cystine in the concentration range of 1.0 x lO " -1.6 X 10 mol at 0.4 V (vs SCE). The mechanism of cysteine oxidation catalyzed by this nanostructured electrode is depicted schematically in Fig. 5.5. Additionally, the electrochemical behavior of Co TsPc nanostructured electrode was more sensitive than those with bare ITO and ITO-Co°TsPc electrodes. 

Fig. 10.7 Proposed inhibition mechanism of cysteine protease inhibitors containing three-mem-bered heterocycles (Hisl59, Cys25 active site diad, papain numbering) [47]...

Helten H, Schirmeister T, Engels B (2004) Theoretical studies about the influence of different ring substituents on the nucleophilic ring opening of three-membered heterocycles and possible implications for the mechanisms of cysteine protease inhibitors. J Org Chem 70(0 223-237... 

There are apparently two distinct enzymic reactions which result in the anaerobic degradation of cysteine. The first is a direct desfilfhydration, the second is initiated by transamination with a-ketoglutarate to yield glutamate and 8-mercaptopyruvate. According to the original observations of Desnuelle and Fromageot, Smythe and others (71) the mechanism of cysteine desulfhydrase action is as follows ... 

B. OXIDATION MECHANISMS OF CYSTEINE SULFUR Direct Oxidation of Cysteine Sulfur... 

Whatever the mechanism of cysteine reduction, it is evident that, if the above reaction takes place, cystine metabolism approaches cysteine metabolism. This is admitted by Pirie (96) in his scheme to illustrate the oxidation of cystine to sulfate by rat liver slices ... 

Other mechanisms of cysteine catabolism have been reported in animals. One such mechanism involves the metaboUsm of cysteine to mercaptopyruvate in a reaction involving amino acid oxidase [Eq. (5)] or aminotransferase activity [Eq. (6)] ... 

FIGURE 24.17 The mechanism of the thiolase reaction. Attack by an enzyme cysteine thiolate group at the /3-carbonyl carbon produces a tetrahedral intermediate, which decomposes with departure of acetyl-CoA, leaving an enzyme thioester intermediate. Attack by the thiol group of a second CoA yields a new (shortened) acyl-CoA. 

Fig. 6.3.9 An illustration showing the mechanism of the reconstitution and luminescence of symplectin. The binding of dehydrocoelenterazine with the SH group of a cysteine residue of aposymplectin (left) results in the formation of active symplectin (center). Symplectin is oxygenated at the C2 position, resulting in the formation of coelenteramide bound to aposymplectin (right), accompanied by the emission of light. From Isobe et al., 2002, with permission from Elsevier.

Proton Pump Inhibitors and Acid Pump Antagonists. Figure 2 Chemical mechanism of irreversible PPIs. PPIs are accumulated in acidic lumen and converted to active sulfenic acid and/or sulfenamide by acid catalysis. These active forms bind to extracytoplasmic cysteines of the gastric H.K-ATPase [3]. 

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. 

XU K and thornalley p j (2000) Studies on the mechanism of the inhihition of human leukaemia cell growth hy dietary isothiocyanates and their cysteine adducts in vitro , Biochem Pharmacol, 60 221-31. 

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