Formation of mercapturic acids in rats after the administration of aralkyl esters

Clapp, J J; Young, L.

doi:10.1042/bj1180765

Cited by 71 publications

(23 citation statements)

References 15 publications

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“…Sodium 1-menaphthyl (napth-1-ylmethyl) sulphate was prepared as described by Clapp & Young (1970). S-(1-Menaphthyl)glutathione was prepared by the method of Hyde & Young (1968).…”

Section: Chemicalsmentioning

confidence: 99%

The mechanism of the reaction between glutathione and 1-menaphthyl sulphate catalysed by a glutathione S-transferase from rat liver

Gillham

1973

Biochemical Journal

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1. The glutathione S-transferase that catalyses the reaction of 1-menaphthyl (naphth-lylmethyl) sulphate with GSH was purified 76-fold from rat liver. 2. The properties of the purified enzyme were studied by gel filtration and isoelectric focusing. 3. The initialvelocity pattern in the absence of products and the product-inhibition pattern have been determined. These are consistent with an Ordered Bi Bi mechanism in which the GSH adds to the enzyme before 1-menaphthyl sulphate and the products are released in the order SO42-followed by S-(1-menaphthyl)glutathione. 4. Dead-end-inhibition studies with p-aminobenzoic acid, which has been shown to be competitive with GSH and noncompetitive with 1-menaphthyl sulphate, support the suggestion that an Ordered Bi Bi mechanism is operative. 5. Values were determined for some of the dissociation and Michaelis constants for the reaction of the substrates and products with the enzyme. 6. It appears that S{1-menaphthyl)glutathione activates the enzyme when the concentration of GSH is saturating and that of 1-menaphthyl sulphate is low (of the order of its Michaelis constant).

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“…Sodium 1-menaphthyl (napth-1-ylmethyl) sulphate was prepared as described by Clapp & Young (1970). S-(1-Menaphthyl)glutathione was prepared by the method of Hyde & Young (1968).…”

Section: Chemicalsmentioning

confidence: 99%

The mechanism of the reaction between glutathione and 1-menaphthyl sulphate catalysed by a glutathione S-transferase from rat liver

Gillham

1973

Biochemical Journal

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“…Chemicals used in enzyme assays were purchased from Aldrich Chemical Co., Sigma Chemical Co. and Boehringer Mannheim. Glutathione reductase is a product of Sigma Chemical Co. 1-Menapthyl sulphate was synthesized by the method of Clapp and Young [10].…”

Section: Methodsmentioning

confidence: 99%

Purification and characterization of a recombinant human Theta-class glutathione transferase (GSTT2-2)

Tan

Board

1996

Biochemical Journal

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A cDNA encoding the human Theta-class glutathione transferase GSTT2-2 was expressed in Escherichia coli as a ubiquitin fusion protein. The co-translational removal of the ubiquitin by a cloned ubiquitin-specific protease, Ubp1, generates enzymically active GSTT2-2 without any additional N-terminal residues. The recombinant isoenzyme was purified to apparent homogeneity by DEAE anion-exchange, gel filtration, dye ligand chromatography and high resolution anion-exchange chromatography on Mono Q FPLC. The recombinant enzyme had significant activity with a range of substrates, including cumene hydroperoxide and 1-menapthyl sulphate. The activity of GSTT2-2 with a range of secondary lipid peroxidation products such as the trans,trans-alka-2,4-dienals and trans-alk-2-enals, as well as its glutathione peroxidase activity with organic hydroperoxides, suggest that it may play a significant role in protection against the products of lipid peroxidation.

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“…It is generally accepted that the broad electrophilic substrate range of the GSTs is related to the high degree of interclass, as well as some intraclass C-terminal domain sequence variation that modulates the shape, composition, and accessibility of the H site~Dirr et al, 1994; Wilce & Parker, 1994!. The mammalian Theta class GSTs exist as two subclasses GSTT1-1 and GSTT2-2!, sharing ;55% sequence identity. Interestingly, both of these subclasses lack activity with the model GST substrate 1-chloro-2,4-dinitrobenzene~CDNB!, which along with their inability to be purified by GSH affinity chromatography has, until recently, restricted the detailed study of this class~Hirat-suka et al, 1990;Meyer et al, 1991!. Despite this, a conjugating activity similar to that of the GSTT2-2 enzyme was the subject of earlier studies concerning the metabolism of aralkyl alcohol, including 1-menaphthyl alcohol, and the corresponding sulfate esters Clapp & Young, 1970;Gillham, 1971!. Furthermore, GSTs exhibiting a specific sulfatase activity toward various carcinogenic sulfate esters and the less harmful 1-menaphthyl sulfate~MSu!…”

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confidence: 99%

Mutagenic analysis of conserved arginine residues in and around the novel sulfate binding pocket of the human Theta class glutathione transferase T2‐2

et al. 1999

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The human Theta class glutathione transferase GSTT2-2 has a novel sulfatase activity that is not dependent on the presence of a conserved hydrogen bond donor in the active site. Initial homology modeling and the crystallographic studies have identified three conserved Arg residues that contribute to the formation of~Arg107 and Arg239!, and entry to~Arg242!, a sulfate binding pocket. These residues have been individually mutated to Ala to investigate their potential role in substrate binding and catalysis. The mutation of Arg107 had a significant detrimental effect on the sulfatase reaction, while the Arg242 mutation caused only a small reduction in sulfatase activity. Surprisingly, the Arg239 had an increased activity resulting from a reduction in stability. Thus, Arg239 appears to play a role in maintaining the architecture of the active site. Electrostatic calculations performed on the wild-type and mutant forms of the enzyme are in good agreement with the experimental results. These findings, along with docking studies, suggest that prior to conjugation, the location of 1-menaphthyl sulfate, a model substrate for the sulfatase reaction, is approximately midway between the position ultimately occupied by the naphthalene ring of 1-menaphthylglutathione and the free sulfate. It is further proposed that the Arg residues in and around the sulfate binding pocket have a role in electrostatic substrate recognition.

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Formation of mercapturic acids in rats after the administration of aralkyl esters

Cited by 71 publications

References 15 publications

The mechanism of the reaction between glutathione and 1-menaphthyl sulphate catalysed by a glutathione S-transferase from rat liver

The mechanism of the reaction between glutathione and 1-menaphthyl sulphate catalysed by a glutathione S-transferase from rat liver

Purification and characterization of a recombinant human Theta-class glutathione transferase (GSTT2-2)

Mutagenic analysis of conserved arginine residues in and around the novel sulfate binding pocket of the human Theta class glutathione transferase T2‐2

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