The hog intestinal mucosa acylase I: Subcellular localization, isolation, kinetic studies and biological function

Giardina, Thierry; Biagini, A.; Ore, F. Dalle; Ferre, E.; Reynier, M; Puigserver, Antoine

doi:10.1016/s0300-9084(97)83514-6

Cited by 38 publications

(44 citation statements)

References 35 publications

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“…For example, the Bacillus stearothermophilus (56), B. thermoglucosidius (14), pig (23), and human (17) enzymes contain one zinc ion per catalytic subunit, while the enzymes from Alcaligenes denitrificans DA181 (61) and Aspergillus oryzae (21) contain two and three zinc ions per subunit, respectively. Like the P. furiosus enzyme, some of these aminoacylases require the addition of a divalent cation (typically Zn, although Co, Mn, and Mg are also effective in some cases) for maximal catalytic activity in vitro (14,21,61), but this is not true for all of them (23,56). However, in all cases, incubation in the presence of EDTA results in complete loss of activity, and this can be restored by the addition of Zn 2ϩ ions.…”

Section: Discussionmentioning

confidence: 99%

Characterization of an Aminoacylase from the Hyperthermophilic Archaeon Pyrococcus furiosus

2001

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The N-terminal amino acid sequence of the purified aminoacylase was used to identify, in the P. furiosus genome database, a gene that encodes 383 amino acids. The gene was cloned and expressed in Escherichia coli by using two approaches. One involved the T7 lac promoter system, in which the recombinant protein was expressed as inclusion bodies. The second approach used the Trx fusion system, and this produced soluble but inactive recombinant protein. Renaturation and reconstitution experiments with Zn 2؉ ions failed to produce catalytically active protein. A survey of databases showed that, in general, organisms that contain a homolog of the P. furiosus aminoacylase (>50% sequence identity) utilize peptide growth substrates, whereas those that do not contain the enzyme are not known to be proteolytic, suggesting a role for the enzyme in primary catabolism.

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Section: Discussionmentioning

confidence: 99%

Characterization of an Aminoacylase from the Hyperthermophilic Archaeon Pyrococcus furiosus

2001

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“…(1,1,2,2-tetrafluoroethyl)-L-cysteine, N-acetyl-S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine, and N-acetyl-S-(2-bromo-1,1,2-trifluoroethyl)-L-cysteine Schneider, 1976, 1977;Heese et al, 1988;Giardina et al, 1997;Uttamsingh et al, 1998;Uttamsingh and Anders, 1999). It was not discovered whether AAI deacetylates the TCE-derived mercapturates.…”

Section: S-alkyl Derivatives Of N-acetyl-l-cysteine Including N-acetymentioning

confidence: 99%

“…Several aminoacylases have been described, including aminoacylase I (AAI; EC 3.5.1.14, N-acylamino acid hydrolase), aminoacylase II (AAII or aspartoacylase; EC 3.5.1.15, N-acyl-L-aspartate amidohydrolase), acyllysine deacylase (EC 3.1.5.17, N -acyl-L-lysine amidohydrolase), and aminoacylase III (AAIII, preferentially mediating deacylation of N-acyl aromatic amino acids). AAI has been purified from mammalian kidney and liver Giardina et al, 1997) and subsequently cloned (Jacob et al, 1992;Mitta et al, 1992;Giardina et al, 2000). AAI is a metalloenzyme, which belongs to the AcyI/M20 family.…”

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confidence: 99%

Specificity of Aminoacylase III-Mediated Deacetylation of Mercapturic Acids

et al. 2006

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ABSTRACT:Trichloroethylene (TCE) and other halogenated alkenes are known environmental contaminants with cytotoxic and nephrotoxic effects, and are potential carcinogens. Their metabolism via the mercapturate metabolic pathway was shown to lead to their detoxification. The final products of this pathway, mercapturic acids or N-acetyl-L-cysteine S-conjugates, are secreted into the lumen in the renal proximal tubule. The proximal tubule may also deacetylate mercapturic acids, and the resulting cysteine S-conjugates are transformed by cysteine S-conjugate ␤-lyases to nephrotoxic reactive thiols. The specificity and rate of mercapturic acid deacetylation may determine the toxicity of certain mercapturic acids; however, the exact enzymologic processes involved are not known in detail. In the present study we characterized the kinetics of the recently cloned mouse aminoacylase III (AAIII) toward a wide spectrum of halogenated mercapturic acids and N-acetylated amino acids. In general, the V max value of AAIII was significantly larger with chlorinated and brominated mercapturic acids, whereas fluorination significantly decreased it. The enzyme deacetylated mercapturic acids derived from the TCE metabolism including N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NA-1,2-DCVC) and N-acetyl-S-(2,2-dichlorovinyl)-L-cysteine (NA-2,2-DCVC). Both mercapturic acids induced cytotoxicity in mouse proximal tubule mPCT cells expressing AAIII, which was decreased by an inhibitor of ␤-lyase, aminooxyacetate. The toxic effect of NA-2,2-DCVC was smaller than that of NA-1,2-DCVC, indicating that factors other than the intracellular activity of AAIII mediate the cytotoxicity of these mercapturic acids. Our results indicate that in proximal tubule cells, AAIII plays an important role in deacetylating several halogenated mercapturic acids, and this process may be involved in their cyto-and nephrotoxicity.Trichloroethylene (TCE) and other industrial solvents are shown to cause nephrotoxicity and hepatotoxicity, and are probable human carcinogens (Maltoni et al., 1988;Cummings and Lash, 2000). One of the TCE toxicity mechanisms involves the conjugation with glutathione, which is transformed by ␥-glutamyltransferase and dipeptidase to cysteine S-conjugates Berrnauer et al., 1996;Anders and Dekant, 1998). The formation of cysteine S-conjugates takes place mainly in liver and, to some extent, also in kidney. Cysteine S-conjugates may be acetylated in the liver and kidney into corresponding N-acetyl S-conjugates (mercapturic acids) and transported from the liver into the kidney. In the kidney proximal tubules, mercapturic acids may be secreted or deacetylated by aminoacylases into cysteine S-conjugates Dekant, 1994, 1998). The deacetylation reaction may play an important role in the renal nephrotoxicity since cysteine S-conjugates, but not mercapturates, are transformed by cysteine conjugate ␤-lyases into toxic metabolites (Hayden and Stevens, 1990;Commandeur et al., 1995). Cysteine S-conjugates also may be transformed by flavoprotein monooxygenase...

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“…The organic phase was dried over anhydrous sodium sulfate and subjected to GC analysis. For the experiments with the 3-S-(N-acetyl-L-cysteinyl)hexanal, 5 mg of acylase I and 10 µM of cobalt chloride were added to the reaction mixture (11).…”

Section: Introductionmentioning

confidence: 99%

Stereochemical Course of the Generation of 3-Mercaptohexanal and 3-Mercaptohexanol by β-Lyase-Catalyzed Cleavage of Cysteine Conjugates

Wakabayashi

Eisenreich

et al. 2003

J. Agric. Food Chem.

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The product resulting from the reaction between E-2-hexenal and l-cysteine was shown to be a diastereoisomeric mixture of 2-(2-S-l-cysteinylpentyl)-1,3-thiazolidine-4-carboxylic acid 1. Treatment of the conjugate with two sources of cysteine-S-conjugate beta-lyase (tryptophanase from E. coli and a crude enzyme extract prepared from Eubacterium limosum) resulted in the formation of 3-mercaptohexanal. The reaction proceeded with a slight preference for the (S)-configured product, however, with low conversion rate. The role of 3-S-l-cysteinylhexanal 2 as substrate for beta-lyases was demonstrated by in situ generation of 2 from 3-S-(N-acetyl-l-cysteinyl)hexanal using acylase. Opposite enantioselectivity was observed for the liberation of 3-mercaptohexanol from 3-S-l-cysteinylhexanol 5 by the enzyme preparations from Eubacterium limosum and tryptophanase. Various yeasts produced 3-mercaptohexanol starting from 1 as well as from 5. The reactions proceeded without preferential formation of one of the enantiomers.

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The hog intestinal mucosa acylase I: Subcellular localization, isolation, kinetic studies and biological function

Cited by 38 publications

References 35 publications

Characterization of an Aminoacylase from the Hyperthermophilic Archaeon Pyrococcus furiosus

Characterization of an Aminoacylase from the Hyperthermophilic Archaeon Pyrococcus furiosus

Specificity of Aminoacylase III-Mediated Deacetylation of Mercapturic Acids

Stereochemical Course of the Generation of 3-Mercaptohexanal and 3-Mercaptohexanol by β-Lyase-Catalyzed Cleavage of Cysteine Conjugates

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