Mercury compounds enzymes containing

The biochemical basis for the toxicity of mercury and mercury compounds resulls from its ability to form covalent bonds with sulfur. Even In low coiiccninilinns divalent mercury is capable of inaelivaiing enzymes containing suirhydrvl I —Nil) groups, causing iiileil crcncc with cellular metabolism and function. 

It is generally accepted that the basis of the biological activity of mercury compounds is their reaction with the thiol groups, but the biological action is rather more complicated. Frank (1955) showed that mercury compounds can influence the effect of enzymes which do not contain thiol groups. Mercury also reacts with the phosphoryl groups of the cell membranes (Bassow et a/., 1961) and with the amino and carboxyl groups of the enzymes (Lipscomb et al., 1968). Webb (1966) lists more than 40 enzymes inhibited by mercury compounds. 

Many bacteria are resistant to inorganic and organic mercury compounds. Mercuric reductase (MerA) is a key enzyme in the mercury detoxification pathway. MerA catalyzes the NADPH-dependent reduction of Hg to its volatile, uncharged, elemental state (Hg ). MerA is a cytosolic protein that is homologous to GR, but also has a short C-terminal extension and a long N-terminal extension not found in GR. MerA contains three pairs of cysteines one in the C-terminal extension, one in the N-terminal extension, and one in the GR-like region of the protein. The N-terminal domain binds one molecule of mercury and delivers it to the catalytic core of the protein, made up of the GR-like portion and the C-terminal extension, where it is reduced. The disulfide from... 

Inorganic and organic mercury compounds have a strong affinity for thiol chemical groups. Most proteins and aU enzymes contain these groups so that mercury readily is bound to body tissues. Most mercury compounds are potent enzyme inhibitors which affects membrane permeability, which in turn affects nerve conduction and tissue respiration. 

Mercuric chloride, other mercury-containing antibacterials and silver will inhibit enzymes in the membrane, and for that matter in the cytoplasm, which contain thiol, -SH, groups. A similar achon is shown by 2-bromo-2-nitropropan-l,3-diol (bronopol) and iso-thiazolones. Under appropriate condihons the toxic action on cell thiol groups may be reversed by addition of an extrinsic thiol compound, for example cysteine or thioglycollic aeid (see also Chapters 12 and 23). 

Enzymes are important targets for mercury [71], and sulphydryl-group-containing enzyme being more sensitive to mercuric compounds than a non sulphydryl-group-containing enzyme [72], Enzymes reported to be inhibited include phosphatases [73, 74], dehydrogenases [75,76] and hexokinases [71]. 

Many of the enzymes in our body are also -SH-containing enzymes, and these will be inactivated if we ingest such compounds. As a result of mercury poisoning, many body functions will be inhibited. 

In contrast, the latter. ryw-isomer, ethyl (TS,2R)-2-(1 -hydroxymethyl)-4-pentenoate. was recently prepared as the only product of a reduction with an enzyme fraction obtained from baker s yeast176. Introduction of a sulfur-containing functional group into the substrate increases stereocontrol in baker s yeast reduction of many ketonesI2e>. 2-Methylthio-3-keto esters are selectively reduced to the (3S)-3-hydroxy esters (Table 5)123,127. The 2-methylthio group is easily removed by 3-chloroperbenzoic acid oxidation to the corresponding sulfoxide followed by subsequent reduction with aluminum-mercury amalgam. Thus, these compounds can also be used for the preparation of optically pure 2-unsubstituted 3-hydroxy esters. 

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