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Mechanism of formation and quantitation of imines, pyrroles, and stable nonpyrrole adducts in 2,5-hexanedione-treated protein.

Authors
DeCaprio-AP; Regan-SJ
Source
Mol Pharmacol 1987 Oct; 32(4):542-548
NIOSHTIC No.
00187027
Abstract
Evidence was presented for an imine intermediate during in-vitro pyrrolylation of bovine-serum-albumin (BSA) by 2,5-hexanedione (110134) (2,5-HD) in aqueous buffer. Quantitative comparisons were also made between total diketone binding and pyrrole adduct formation as a function of both pH and diketone/amine molar ratio. The findings were consistent with the appearance of nonpyrrole reaction products at high diketone/amine molar excess but not at lower, more physiologically relevant, ratios. The sensitivity and effectiveness of the p-dimethylaminobenzaldehyde (DMAB) assay in the detection of pyrrole adducts was confirmed. The possible significance of these in-vitro findings was discussed in relation to the proposed mechanisms of action of the neurotoxic gamma-diketones. Certain generalizations could be drawn from this study. It appeared that at the relatively low levels of lysine conservation likely to be present after 2,5-HD exposure in-vivo, the DMAB assay can accurately assess protein pyrrole adduct concentrations. Evidence was provided that pyrrolylation can result in significant alterations in protein structure, particularly in those species not constrained by multiple disulfide linkages, an effect presumably related to the extreme hydrophobicity of this derivative.
Keywords
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Ketones; Amines; Neuropathology; Pyrroles; In-vitro-studies;
Contact
Biochem and Genetic Toxicology New York State Dept of Health Empire State Plaza Albany, N Y 12201
CODEN
MOPMA3
CAS No.
110-13-4;
Publication Date
19871001
Document Type
Journal Article;
Funding Amount
133853.00
Funding Type
Grant;
Fiscal Year
1988
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-01972
Issue of Publication
4
ISSN
0026-895X
Priority Area
Neurotoxic Disorders; Neurotoxic-effects;
Source Name
Molecular Pharmacology
State
NY;
Performing Organization
New York State Dept of Health, New York, New York
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