Enzymes sulfhydryl

The biochemical basis for the toxicity of mercury and mercury compounds results from its ability to form covalent bonds readily with sulfur. Prior to reaction with sulfur, however, the mercury must be metabolized to the divalent cation. When the sulfur is in the form of a sulfhydryl (— SH) group, divalent mercury replaces the hydrogen atom to form mercaptides, X—Hg— SR and Hg(SR)2, where X is an electronegative radical and R is protein (36). Sulfhydryl compounds are called mercaptans because of their ability to capture mercury. Even in low concentrations divalent mercury is capable of inactivating sulfhydryl enzymes and thus causes interference with cellular metaboHsm and function (31—34). Mercury also combines with other ligands of physiological importance such as phosphoryl, carboxyl, amide, and amine groups. It is unclear whether these latter interactions contribute to its toxicity (31,36). 

Structural Formula Chymopapain Is a sulfhydryl enzyme similar to papain. Has components of molecular weight about 35,000. 

Armstrong, D.A. and Buchanan, J.D. (1978). Reactions of O2, H2O2 and other oxidants with sulfhydryl enzymes. Photochem. Photobiol. 28, 743-755. 

The reactivity of thiols has been studied in connection with the catalytic function of sulfhydryl enzymes. When nucleophilic reactions of thiolate anions towards PNPA were compared, the thiolate reactivity in vitro was always very small relative to those observed in vivo. Although the details of enzymatic activation mechanisms are far from clear, there is general agreement that this large difference can be attributed to differing microenvironments around the SH group. 

There are a few common and long-known uses of heavy metal compounds which should be mentioned. The barium meal is used in gastrointestinal X-rays. It is administered as barium sulfate, the high electron scattering of barium ions providing X-ray opacity. Mercurial diuretics, derivatives of propan-2-ol, work by inhibition of sulfhydryl enzyme sites. These compounds are now becoming obsolete, however. 

The CO—NH amide bond is relatively energy-rich and can be hydrolyzed to free carboxylic acids and ammonia, by a variety of unrelated or distantly related enzymes, called amidases. Most of amidases are sulfhydryl enzymes like all members of the nitrilase superfamily, while other amidases such as those from Pseudomonas... 

Some of the basic information on stabilizing sulfhydryl enzymes, has been responsible for their commercialization. Without the judicious use of reducing compounds throughout the processing of the papaya latex, it would not have been possible to maximize the proteolytic activity of commercial papain preparations. Examples of other studies of enzymes which have contributed to commercialization are the determination of calcium ion as a requirement for amylase stability at high temperature, the difference in properties of catalases derived from bacterial, fungal, or... 

As(ni) reversibly binds to sulfhydryl groups, and inhibits critical sulfhydryl enzyme systems. 

Because of the results found with p-(chloromercuri)benzoate and because /3-galactosidase is believed to be a sulfhydryl enzyme, it seemed advisable to investigate the effects of other sulfhydryl reagents. Virtually no inhibition of /3-galactosidase was found in the presence of iodoacetam-ide (9 X 10 M) over a period of 7 hours. A -Phenylmaleimide, at concentrations as high as 8.7 X 10 M, produced less than 10 % inhibition over a 20-hour period. However, when the concentration of V-phenyl-maleimide was raised to 9.1 X 10 M, assay of the incubation mixture revealed that 50% inhibition of /3-galactosidase occurred within a 2-hour period when the experiment was performed in 2-amino-2-(hydroxymethyl)-1,3-propanediol— acetic acid buffer, pH 8.0. Virtually no activity was lost when the latter experiment was repeated in phosphate buffer (Na salts) at the same pH. 

Several sulfhydryl enzymes have been modified specifically by halo-ketones. They include clostripain, papain, ficin, and bromelain (Porter et al. 1971 Whitaker and Perez-Villasenor 1968 Stein and Liener 1967 Murachi and Kato 1967). For these enzymes, the chloro-methylketone of N-tosyl-phenylalanine and N-tosyl-lysine were used as the site-specific modification reagents. The derivatives formed by the alkylation of cysteine by haloketones do not regenerate cysteine... 

Excess selenium results in liver atrophy, necrosis, and hemorrhage. The mechanism of toxicity is unknown but may involve redox cycling. Sulfhydryl enzymes are attacked by soluble selenium compounds. 

Gargouri, Y, Moreau, H., Pieroni, G. and Verger, R. (1988) Human gastric lipase A sulfhydryl enzyme. J. Biol. Chem. 

One theory of the mechanism of acute selenium toxicity concerns inactivation of the sulfhydryl enzymes necessary for the oxidative reactions in cellular respiration (Lombeck et al. 1987 Mack 1990 Shamberger 1981). Acute toxic effects, such as pulmonary edema, can result in respiratory failure and death. The lung, however, does not appear to be a target organ at levels of exposure less than the occupational permissible exposure limits (PELs) or threshold limit values (TLV). 

The present classes of diuretic drugs have contributed much useful information to the chemist and to the biologist. From the mercurial diuretics, on the biological side, some facts have been learned about their site of action, if not the exact mechanism of action, and they have been helpful in the study of the site of the transport of various ions by the kidney. The importance of sulfhydryl enzyme systems has been demonstrated, although the specific enzyme has not been identified. On the chemical side, the chemist has learned about the structural requirements for useful activity, the nature of the carbon-mercury attachment, and the organic structures most useful as carrying moieties for mercury. 

Thus, allicin has been found to inhibit a large number of enzymes in vitro if they contain cysteine at the active sites, but otherwise very few (Lawson, in Koch and Lawson, 1996, p. 65). The reference further states that many of the explanations given for the biological effects of garlic focus on the ability of allicin to react with sulfhydryl enzymes, whatever the latter may be. Moreover, allicin was found to act against cholesterol and triglyceride synthesis. 

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