THE PRODUCTION OF FORMALDEHYDE FROM THE INTERACTION OF DIMETHYLSULFOXIDE WITH HYDROXYL RADICALS: APPLICATION TO THE DETECTION OF HYDROXYL RADICALS IN BIOLOGICAL SYSTEMS AND ITS USE IN EVALUATING THE MOLECULAR MECHANISM OF THE MICROSOMAL ETHANOL OXIDIZING SYSTEM.
Item
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Title
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THE PRODUCTION OF FORMALDEHYDE FROM THE INTERACTION OF DIMETHYLSULFOXIDE WITH HYDROXYL RADICALS: APPLICATION TO THE DETECTION OF HYDROXYL RADICALS IN BIOLOGICAL SYSTEMS AND ITS USE IN EVALUATING THE MOLECULAR MECHANISM OF THE MICROSOMAL ETHANOL OXIDIZING SYSTEM.
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Identifier
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AAI8222954
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identifier
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8222954
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Creator
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KLEIN, SHELLEY MIRIAM.
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Contributor
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Arthur Cederbaum
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Date
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1982
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Biochemistry
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Abstract
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Dimethylsulfoxide (Me(,2)SO) is a potent hydroxyl radical ((.)OH) scavenging agent. The production of methane from Me(,2)SO has been used to detect the generation of (.)OH in biological systems. Evidence is presented which demonstrates that formaldehyde is produced during the interaction of Me(,2)SO with (.)OH generated by three different systems. These systems were (1) the oxidation of xanthine by xanthine oxidase, (enzymatic system) (2) the iron-catalyzed oxidation of ascorbic acid, (chemical system) and (3) NADPH-dependent electron transfer by rat liver microsomes, (biological membrane system). In all three systems, formaldehyde, rather than methane, represents a major product of this interaction. Formaldehyde production was inhibited by (.)OH scavenging agents. It appears that (.)OH is generated by these systems via a Fenton reaction in which the reduction of iron is brought about either by superoxide radicals (xanthine oxidase and microsomes) or by ascorbate (ascorbate system). The mechanism of microsomal (.)OH generation is dissociated from the classical cytochrome P-450 drug metabolizing pathway.;The activity of the microsomal ethanol oxidizing system is increased after chronic ethanol consumption. The mechanism responsible for this increase is not known. Rat liver microsomes from ethanol-fed rats oxidized Me(,2)SO and 2-keto-4-thiomethylbutyric acid (KTBA) at rates which were two-to-three-fold faster than microsomes obtained from pair-fed controls. This increased rate of (.)OH production correlated with an increased rate of ethanol oxidation. Cross competition among ethanol, Me(,2)SO and KTBA for oxidation and inhibition by other (.)OH scavenging agents was observed in both microsomal preparations. The increased rate of (.)OH production by microsomes obtained from chronic ethanol-fed rats may be responsible, at least in part, for the increased rate of ethanol oxidation.;The production of formaldehyde from Me(,2)SO may represent a convenient technique to detect and to evaluate the role of (.)OH in some biological systems such as intact cells or In vivo. In view of the production of formaldehyde, Me(,2)SO should not be considered to be an inert solvent in biological systems.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
