Hydrolases induction

Host 3-Glucan Hydrolase Induction. A further response to microbial invasion of host tissues involves an increase in activity of certain host enzymes, especially the glycan hydrolases which are potentially able to depolymerise microbial polysaccharides. 

Fig. 3. Diagrammatic representation of the possible mechanisms underlying acid hydrolase induction. A. Endocytosis and/or phagolysosome formation stimulates ( intermediate) DNA-RNA mechanism. B. DNA-RNA machinery is stimulated through a membrane activated second messenger. C. Direct stimulation of protein-synthesizing system by inducer molecule.

It is reasonable that the process of vesiculation occurs at an equilibrium rate, constant for each cell species and modified by the metabolic demands of the cells. We have suggested (Verity and Brown, 1968b), from maturation studies of cerebral lysosomal enzymes, that for a given rate of vesiculation, the enzyme complement of the primary lysosome is directly proportional to the individual rates of synthesis of the component enzymes. Such a hypothesis would account for the heterogeneity in acid hydrolase reaction to injury, the difference in maturation profiles of individual acid hydrolases, and the dysynchrony of acid hydrolase induction. Also suggested is a direct feedback mechanism whereby a stimulation of vesiculation may in turn induce increased enzyme synthesis, possibly through changes in membrane phospholipid metabolism. 

Boiler, T. (1985). Induction of hydrolases as a reaction against pathogens. In... 

Emphasis is given to the critical role of metabolism, both detoxication and activation, in determining toxicity. The principal enzymes involved are described, including monooxygenases, esterases, epoxide hydrolases, glutathione-5 -transferases, and glucuronyl transferases. Attention is given to the influence of enzyme induction and enzyme inhibition on toxicity. 

Parkinson, A., Thomas, P.E., Ryan, D.E. etal. (1983) Differential time course of induction of rat liver microsomal cytochrome P 450 isozymes and epoxide hydrolase by Aroclor 1254. Archives of Biochemistry and Biophysics, 225, 203-215. 

It is noteworthy that, in contrast to mammalian systems, the majority of bacterial strains exhibited sufficient activity even when the cells were grown under non-optimized conditions. Since enzyme induction is still a largely empirical task, cells were grown on standard media in the absence of inducers. Furthermore, all attempts to induce epoxide hydrolase activity in Pseudomonas aeruginosa NCIMB 9571 and Pseudomonas oleovorans ATCC 29347 by growing the cells on an alkane (decane) or alkene (1-octene) as the sole carbon source failed [27]. 

Kawashima Y, Uy-Yu N, Kozuka H Sex-related difference in the inductions by perfluorooctanoic acid of peroxisomal fl-oxidation, microsomal 1-acylglycerophos-phocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver. Biochem J 26 595-6Q0, 1989... 

Lin TS, Kolattukudy PE (1978) Induction of a biopolyester hydrolase (cutinase) by low levels of cutin monomers in Fusarium solani f sp. pisi. J Bacteriol 133 942-951... 

Poland A, Glover E, Kende AS. 1976. Stereospecific, high affinity binding of 2,3,7,8-tetra-chlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydrolase. J Biol Chem 251 4936-4946. 

Thomas H, Timms CW, Oesch F. Epoxide hydrolases molecular properties, induction, polymorphisms and function. In Ruckpaul K, Rein H, eds. Frontiers of Bio transformation. Vol. II. Principles, Mechanisms and Biological Consequences of Induction. London Taylor Francis, 1990. 

Although first reported with the cytochrome(s) P-450 mixed function oxidases, it is now known that a number of the enzymes involved in the metabolism of foreign compounds are inducible. Thus, as well as the CYPs, NADPH cytochrome P-450 reductase, cytochrome b5, glucuronosyl transferases, epoxide hydrolases, and GSTs are also induced to various degrees. However, this discussion concentrates on the induction of the CYPs with mention of other enzymes where appropriate. 

As well as detoxication via reaction with GSH, the reactive 3,4-epoxide can be removed by hydration to form the dihydrodiol, a reaction that is catalyzed by epoxide hydrolase (also known as epoxide hydratase). This enzyme is induced by pretreatment of animals with the polycyclic hydrocarbon 3-methylcholanthrene, as can be seen from the increased excretion of 4-bromophenyldihydrodiol (Table 7.5). This induction of a detoxication pathway offers a partial explanation for the decreased hepatotoxicity of bromobenzene observed in such animals. A further explanation, also apparent from the urinary metabolites, is the induction of the form of cytochrome P-450 that catalyzes the formation of the 2,3-epoxide. This potentially reactive metabolite readily rearranges to 2-bromophenol, and hence there is increased excretion of 2-bromophenol in these pretreated animals (Table 7.5). 

Gill SS, Kaur S. 1987. Hepatic epoxide hydrolase activities and their induction by clofibrate and dicthylhcxylphthalatc in various strains ofmice. Biochem Pharmacol 36 4221-4227. 

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