Oxidants, enzyme inactivation inhibition

Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation.

Mechanism of action of S-adenosylhomoeysteine hydrolase (enzyme) and its inhibition by deoxyadenosine. (a) The enzyme uses enzyme-bound NAD+ to temporarily oxidize substrate and eventually hydrolyze it to adenosine and homocysteine. [Reproduced with permission from R. H. Abeles, Suicide enzyme inactivators. Chem. Eng. News 61(38), 55 (September 19, 1983). 1983 by the American Chemical Society.] (b) Deoxyadenosine, a suicide substrate, is also oxidized by the enzyme with the formation of a ketosugar, which undergoes decomposition, with the product dissociating from the enzyme and leaving the enzyme in the reduced state (NADH). 

Rubbo, H., Denicola, A., and Radi, R. (1994a). Peroxynitrite inactivates thiol-containing enzymes of T. cruzi oxidative metabolism and inhibits cell respiration. Arch. Biochem. Biophys. 308, 96-102. 

The enzyme is inactivated rapidly by air and other oxidants, but the activity may be restored by anaerobic incubation of the enzyme with reducing agents or Fe ions. The enzyme is inhibited by iron chelating agents such as a,a -dipyridyl. 

Kim K, Kim IH, Lee KY et aL The isolation and purification of a specific protector protein which inhibits enzyme inactivation by a thiol/Fe(III)/02 mixed-function oxidation system. J Biol Chem 1988 263 4704-4711. 

The microbiostatic action of benzoic acid is based on different inhibition mechanisms, mainly many enzymes in the microbial cell are inhibited (Bosund, 1962 Menon et al., 1990). E.g. in yeast, enzymes that control the acetic acid metabolism and oxidative phosphorylation are inhibited. Benzoic acid appears to intervene at various points in the citric acid cycle, especially that of a-ketoglutaric acid and succinic acid dehydrogenase. Besides its enzyme-inactivating effects, benzoic acid also acts on the cell wall. The types of action of benzoic acid are sometimes very similar to those of sorbic acid, although many more data exist for the latter. 

A hyaluronate lyase from group A Streptococci has been purified (1000-fold) by ion-exchange chromatography and gel filtration two fractions with identical amino-acid compositions were obtained. The enzyme was inhibited by A-(toIuene-/7-sulphonyl)phenylalanine chloromethyl ketone and iV-(toluene-p-sulphonyl)lysine, and did not depolymerize hyaluronic acid methyl ester. Photo-oxidation in the presence of Methylene Blue inactivated the enzyme, whose action probably involves the transfer of a proton between a histidyl residue of the enzyme and a carboxy-group of the substrate. 

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