Metal ions sulfhydryl groups

At the cellular level, toxicity may result from binding of metals to sulfhydryl groups in proteins, thereby inhibiting enzyme activity or protein function, or by producing a deficiency of other essential ions. Other possibilities include disruption of cell transport processes and oxidative damage (Williams et al. 2000). 

The vast majority of biochemical processes in which a metal plays a role involve a only a relatively small number of metals. Those metals include Na, K, Mg, Ca, Mo, or the first-row transition metals from V to Zn. Only molybdenum could be considered as a heavy metal. It should also be observed that the metal ions constitute those that can be considered as hard or borderline in hardness. It is a general property that ions of heavy metals having low charge (that is to say "soft") are toxic. These include Hg, Pb, Cd, H, and numerous others. Some heavy metals bind to groups such as the sulfhydryl (-SH) group in enzymes, thereby destroying the ability of the enzyme to promote the reaction in a... 

The inhibition of G-6-PDH and 6-PGDH by heavy metal ions and its reversibility by adding EDTA demonstrates the requirement of active sulfhydryl groups (GIO, R6). This finding is confirmed by the activating action of cysteine (N2, W18). However, an inhibition of... 

It is usually believed that NO inhibits enzymes by reacting with heme or nonheme iron or copper or via the S-nitrosilation or oxidation of sulfhydryl groups, although precise mechanisms are not always evident. By the use of ESR spectroscopy, Ichimori et al. [76] has showed that NO reacts with the sulfur atom coordinated to the xanthine oxidase molybdenum center, converting xanthine oxidase into a desulfo-type enzyme. Similarly, Sommer et al. [79] proposed that nitric oxide and superoxide inhibited calcineurin, one of the major serine and threonine phosphatases, by oxidation of metal ions or thiols. 

Additional examples of type d (Scheme 5.1) bifunctional reactants are provided by the alkaline-earth metal ion complexes of lariat ethers 8-10, bearing a sulfhydryl side arm, instead ofthe phenolic hydroxyl of a calixcrown [23,24]. Here the acyl-receiving and acyl-releasing unit, like in papain and ficin, is a sulfhydryl group. 

Irreversible Inhibition of an Enzyme Many enzymes are inhibited irreversibly by heavy metal ions such as Hg2+, Cu2+, or Ag+, which can react with essential sulfhydryl groups to form mercaptides ... 

Gal has a molecular weight of 540,000 and is composed of four identical subunits of MW 135,000, each with an independent active site (Melchers and Messer, 1973). The enzyme has divalent metals as cofactors, with chelated Mg2 h ions required to maintain active site conformation. The presence of NaCl or dilute solutions (5%) of low-molecular-weight alcohols (methanol, ethanol, etc.) causes enhanced substrate turnover. (3-Gal contains numerous sulfhydryl groups and is glycosylated. 

The oxidants responsible for initiating LDL oxidation have been under intense investigation, and several possible mechanisms have been suggested. For example, Oj has been implicated as a major contributor to LDL oxidation mediated by macrophages and smooth muscle cells (H8). Here, O " is converted to H2O2 by SOD, which in turn is acted upon by a transition metal ion with the formation of HO. Another possible role for Cff is its reaction with NO to form ONOCT, which is capable of oxidizing lipids and sulfhydryl groups, even in the presence of plasma antioxidants (VI). Moreover, in vitro studies have shown that ONOCT can induce the formation of F2-isoprostanes, nonenzymatic products of the free radical-catalyzed oxidation of arachidonic acid (M13). 

The activity of the enzyme is also strongly affected by the presence of inhibitors. Fluoride ions inhibit urease (173) and oxalate ions inhibit lactate oxidase (174), but the major inhibitors are heavy-metal ions, such as Ag+, Hg +, Cu " ", organophosphates, and sulfhydryl reagents (/i-chloromercuribenzoate and phenylmercury(II) acetate), which block the free thiol groups of many enzyme active centers, especially oxidase (69). Inhibiting the enzyme electrodes makes it possible to quantify the inhibitors themselves (69), for example, H2S and HCN detection using a cytochrome oxidase immobilized electrode (176). 

In response to the presence of detrimental Cd +, Hg +, Pb +, and other heavy metal ions, the human hver and kidneys synthesize more metallothionein, an unusual small protein in which approximately one-third of the 61 amino acid residues are cysteine see Metallothioneins). The frequency and juxtaposition of sulfhydryl groups provide strong binding sites for several heavy metal ions. Though not as profusely as metallothionein, many proteins contain sulfhydryl groups that may become metalated by toxic heavy metal ions such as Cd +, Hg +, and Pb +, and it is widely believed that this complex formation explains the toxicity of these metal ions. The exact proteins where the most consequential damage occurs remain uncertain. 

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