Sulphydryl group inhibition

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]. 

Mercury can influence ion, water, and nonelectrolyte transport in different cells [ 14, 77]. The cell membrane is believed to be the first point of attack by heavy metals however, intracellular enzymes and metabolic processes may also be inhibited [70, 78, 79]. The attachment of heavy metals to ligands in or on the plasma membrane may result in changes in passive permeability or selective blockage of specific transport processes. Many membrane transport systems are known to be sensitive to sulphydryl-group modification [ 14, 80, 81]. 

Mercuric chloride has also been shown to inhibit the enzymatic activity of soluble protein kinase A from mice brain, apparently by binding to sulphydryl groups of the enzyme [111]. The inhibition was of a non-competitive type with respect to HI histone. 

Mercury and nickel salts form many stable complexes with biologically important molecules such as those containing sulphydryl groups Chapter 5 stresses the importance and the dangers of these being formed in the skin from topical contact. The last 10 years have been a highly fertile and productive period in the discovery of antibacterial quinolones (reviewed in Chapter 6) which inhibit target enzymes at the molecular level. 

Both compounds interfere with purine biosynthesis at one of the three stages where glutamine is required. Addition of either of these two inhibitors to cells leads to an accumulation of formylglycineamide ribotide. The inhibition of the enzyme is reversible for a short period but soon becomes irreversible as a result of the inhibitor alkylating the enzyme, probably through a sulphydryl group of a cysteine residue. 

Heptinstall, S., Groenewegen, W., Spangenberg, P., and Loesche, W. 1987. Extracts of feverfew may inhibit platelet behavior via neutralization of sulphydryl groups. J. Pharm. Pharmacol. 39, 459-465. 

The depletion of glutathione and NADPH will allow the oxidation of protein sulphydryl groups, which may be an important step in the toxicity. Thus, glutathione and protein sulphydryl groups, such as those on Ca2+ transporting proteins, are important for the maintenance of intracellular calcium homeostasis. Thus, paracetamol and NAPQI cause an increase in cytosolic calcium and paracetamol inhibits the Na+/ K+ ATPase pump in isolated hepatocytes. 

Mercury is a reactive element and its toxicity is probably due to interaction with proteins. Mercury has a particular affinity for sulphydryl groups in proteins and consequently is an inhibitor of various enzymes such as membrane ATPase, which are sulphydryl dependent. It can also react with amino, phosphoryl and carboxyl groups. Brain pyruvate metabolism is known to be inhibited by mercury, as are lactate dehydrogenase and fatty acid synthetase. The accumulation of mercury in lysosomes increases the activity of lysomal acid phosphatase which may be a cause of toxicity as lysosomal damage releases various hydrolytic enzymes into the cell, which can then cause cellular damage. Mercury accumulates in the kidney and is believed to cause uncoupling of oxidative phsophorylation in the mitochondria of the kidney cells. Thus, a number of mitochondrial enzymes are inhibited by Hg2+. These effects on the mitochondria will lead to a reduction of respiratory control in the renal cells and their functions such as solute reabsorption, will be compromised. 

Omepra/ole and lansopraznie are inactive at neutral pH. but in acid they rearrange into two types of reactive molecule, which react with sulphydryl groups in the H7K -ATPproton pump) responsible for transporting H" ions out of the parietal cells. Because the enzyme is irreversibly inhibited, acid secretion only resumes after the synthesis of... 

Heptinstall, S., W.A. Groenewegen, P. Spangenberg, and W. Losche. 1988. Inhibition of platelet behaviour by feverfew A mechanism of action involving sulphydryl groups. Folia Haematol. Int. Mag. Klin. Morphol. Bluforsch. 115(4) 447-449. Johnson, E.S. 1983. Patients who chew chrysanthemum leaves. MIMS Mag. (May 15) 32-35. 

The poisoning effect of mercury(//) ions is probably due to its binding with sulphydryl groups on proteins inhibiting enzyme activity. Therefore, the effective concentration of added mercury is highly dependent on the concentration of organic material and on the... 

Ten strains of Propionibacterium shermanii have been tested for jS-D-galacto-sidase activity against 2-nitrophenyl jS-o-galactopyranoside the relation between the production of the enzyme and the stage of growth was examined. The enzyme was inhibited by blocking of its sulphydryl groups, but this inhibition was partly reversed with 1,4-dithiothreitol. 

The purity of four isoenzymes of an a-amylase isolated from red spring wheat has been established by chromatography, electrophoresis, and sedimentation studies. The isoenzymes have identical diffusion coefficients, molecular weights [4.51 x 10 (by sedimentation) and 4.20 x 10 (by electrophoresis)], pi values (6.05—6.20), and pH optima (5.6—5.5). The proteins contain relatively large proportions of glutamic and aspartic acids, but no sulphydryl groups. The inhibition of wheat a-amylase by L-ascorbic acid and derivatives of isoalloxazine has been studied. ... 

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