Sulfhydryl group of enzymes

Several mechanisms have been postulated to account for thallium s toxicity, including ligand formation with sulfhydryl groups of enzymes and transport proteins, inhibition of cellular respiration, interaction with riboflavin and riboflavin-based cofactors, alteration of the activity of K -dependent proteins, and disruption of intracellular calcium homeostasis. ... 

Quinone reacts with the sulfhydryl groups of enzymes snch as amylase and carboxylase. This reaction interferes with their activity and, indirectly, with other cellnlar processes such as oxidative phosphorylation. Chloranil and dichlone have been discontinued and are no longer available in the U.S. 

The cytotoxicity of these compounds is due to a very reactive centre in the molecule, the exocyclic ot.-methylene-/ -lacton group which may easily add to sulfhydryl groups of enzymes or other proteins (32, 34, 35). Therefore, cystein applied immediately has been shown to be a useful antidot in hamsters (34). Tenulin, which is less toxic than the other compounds lacks this methylenelacton group it possesses an ac,6-unsaturated keto group in the cyclopentane ring, as is found in many toxins and carcinogens. 

D. Heavy Metals Mercury and silver precipitate proteins and inactivate sulfhydryl groups of enzymes but are used rarely because of toxicity. Organic mercurials such as nitromersol and thimerosal frequently cause hypersensitivity reactions but continue to be used as preservatives for vaccines, antitoxins, and immune sera. Merbromin is a weak antiseptic and stains tissues a bright red color. In the past silver nitrate was commonly used for prevention of neonatal gonococcal ophthalmia, but it has been largely replaced by topical antibiotics. Silver sulfadiazine (a sulfonamide) is used to decrease bacterial colonization in bums. 

The metals discussed in this chapter—lead, arsenic, mercury, and iron—frequently cause significant toxicity in humans. The toxicity profiles of metals differ, but most of their effects appear to result from interaction with sulfhydryl groups of enzymes and regulatory proteins. Chelators are organic compounds with two or more electronegative groups that can form stable covalent-coordinate bonds with cationic metal atoms. As emphasized in this chapter, these stable complexes can often be excreted readily, thus reducing the toxicity of the metal. 

Arsenic As Impairment of growth and reproduction (animals) Poisonous Blocks sulfhydryl groups of enzymes... 

All the individual steps are catalyzed by enzymes NAD" (Section 15 11) is required as an oxidizing agent and coenzyme A (Figure 26 16) is the acetyl group acceptor Coen zyme A is a thiol its chain terminates m a sulfhydryl (—SH) group Acetylation of the sulfhydryl group of coenzyme A gives acetyl coenzyme A... 

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

Mode of Action. The fundamental biochemical lesion produced by arsenicals is the result of reaction between As " and the sulfhydryl groups of key respiratory enzymes such as pymvate and a-ketoglutarate dehydrogenases. 

A comparison of the structures of penicillin and Dalanyl-Dalanine (cf. structures 41 and 42) shows that there is a great deal of similarity between the two molecules. Penicillin is essentially an acylated cyclic dipeptide of Dcysteine and Dvaline (84). As such, it contains a peptide bond, that of the /3-lactam ring, that can acylate the enzyme. Labeling studies of the peptidoglycan transpeptidase of Bacillus subtilis indicate that radioactive penicillin reacts with a sulfhydryl group of a cysteine residue of the enzyme (86). 

Heavy metals with no known biological function, such as aluminum, arsenic, lead, and mercury, are nonessential metals.4-5 These metals are toxic because they can irreversibly bind to enzymes that require metal cofactors. Toxic metals readily bind to sulfhydryl groups of proteins.6-7 In fact,... 

The application of magnetic resonance techniques to biological systems is a relatively new approach for the study of macromolecules. In this review we have presented the different approaches which have been made to study Bi2-enzymes. Clearly some progress has been made particularly from the application of ESR to a study of the enzymes ethanolamine ammonia-lyase and ribonucleotide reductase. Although 13C NMR is well in its developmental stages it is obvious that this technique will prove to be very useful for the examination of coenzyme-enzyme interactions. Studies of how corrinoids bind in enzymes and how sulfhydryl containing proteins are involved in enzyme catalysis comprise two major problems which must be overcome before realistic mechanisms can be presented for this group of enzymes. 

Tin is shown to be methylated by organisms and other environmental factors. Organic tin compounds are much more toxic than the inorganic ones. This increase in toxicity due, e.g., to methylation is attributable to the increasing membrane permeability of the methylated metal compounds and to the remaining sensibility to react with sulfhydryl groups of proteins, especially of enzyme proteins. 

Papain is readily inactivated by PAN (at 115 ppm for 40 min), provided that it is in the sulfhydryl form. The reaction of sulfhydryl groups of hemoglobin with PAN is very similar to the reaction with p-mercuricbenzoate there is more reaction at a pH of 4.5 than at a pH of 7. However, there is one striking difference between PAN and classic compounds that react with sulfhydryl groups egg albumen is resistant to reaction with PAN. Thus, enzymes that have no free sulfhydryl groups should be quite resistant to PAN. This is the case with pancreatic ribonuclease the native enzyme was not affected by a 300-fold molar excess of PAN. 

During the reaction, acetate, or the growing fatty acyl chain is initially esteri-fied to the sulfhydryl group of a cysteine residue of the enzyme. 

The 2-chloroacetanilides (Figure 2.22) are also suggested to inhibit cell division in susceptible weeds. These compounds have found a major commercial market for the pre-emergence control of grass and some small seeded broad-leaved weeds in crops such as maize and soybean. It is likely that 2-chloroacetanilides also alkylate the sulfhydryl groups of certain essential plant enzymes. 

Regeneration of reduced enzyme In order for ribonucleotide reductase to continue to produce deoxyribonucleotides, the disulfide bond created during the production of the 2 -deoxy carbon must be reduced. The source of the reducing equivalents is thioredoxin—a peptide coenzyme of ribonucleotide reductase. Thioredoxin contains two cysteine residues separated by two amino acids in the peptide chain. The two sulfhydryl groups of thioredoxin donate their hydrogen atoms to ribonucleotide reductase, in the process forming a disulfide bond (see p. 19). 

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