TY - JOUR
T1 - Oxidation of isopropanol by rat liver microsomes. Possible role of hydroxyl radicals
AU - Cederbaum, Arthur I.
AU - Qureshi, Aziz
AU - Messenger, Philip
N1 - Funding Information:
Isolated rat liver microsomes are capable of oxidizing a series of straight chain aliphatic alcohols, such as methanol, ethanol, propanol and butanol, to the corresponding aldehydes \[1, 2\]. In the presence of an H202-generating system, virtually no aldehydes were produced with propanol and butanol as substrates \[1, 2\]. These longer chain alcohols function poorly as substrates for the peroxidatic activity of catalase \[3-5\]A. role for a cytochrome P-450 dependent pathway in the oxidation of alcohols by microsomes has been demonstrated \[6--9\].R ecent experiments from our laboratory indicated that the NADPH-dependent oxidation of ethanol by rat liver microsomes was inhibited by a series of hydroxyl radical (.OH)§ scavengers in the presence of azide, an inhibitor of catalase \[10-12\]. These .OH scavengers had no effect on microsomal electron transfer or drug metabolism \[10-12\].T hree chemical probes were used to detect .OH production by liver microsomes; microsomes generated ethylene gas from methional and KTBA, and methane gas from Me2SO \[12, 13\]. These experiments suggested that the oxi- *These studies were supported by USPHS Grants AA-03312 and AA-04413 and by Research Scientist Career Development Award 5K02-AA-00003 (A. I. C.). t Author to whom all correspondence should be addressed: Department of Biochemistry, Mt. Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, U.S.A. :~ Mount Sinai (1979) volunteer. § Abbreviations: .OH, hydroxyl radical; KTBA, 2-keto-4-thiomethylbutyric acid; and Me2SO, dimethylsulfoxide.
PY - 1981/4/15
Y1 - 1981/4/15
N2 - Isopropanol, a branched chain alcohol, served as a substrate for the microsomal alcohol oxidizing system. Isopropanol oxidation required NADPH; H2O2 or an H2O2-generating system did not effectively support isopropanol oxidation, indicating that isopropanol was not a substrate for the peroxidatic activity of catalase. The addition of azide by itself or H2O2 (in the presence of azide and NADPH) stimulated isopropanol oxidation, suggesting a pivotal, indirect role for H2O2 in the system. H2O2 may serve as a precursor of hydroxyl radicals. Accordingly, the oxidation of isopropanol was inhibited by hydroxyl radical scavenging agents, namely dimethylsulfoxide, mannitol, benzoate and 2-keto-4-thiomethylbutyric acid. Fe-EDTA, which is known to increase hydroxyl radical generation, stimulated the oxidation of isopropanol. The stimulation by Fe-EDTA was blocked by competing hydroxyl radical scavengers. Model hydroxyl radical generating systems such as the coupled oxidation of xanthine by xanthine oxidase, especially in the presence of Fe-EDTA, or the autoxidation of ascorbate in the presence of Fe-EDTA could also oxidize isopropanol. These results indicate that (a) rat liver microsomes are capable of oxidizing branched chain alcohols, and (b) hydroxyl radicals or a species with the oxidizing power of the hydroxyl radical, generated from microsomal electron transfer, may play a role in isopropanol oxidation.
AB - Isopropanol, a branched chain alcohol, served as a substrate for the microsomal alcohol oxidizing system. Isopropanol oxidation required NADPH; H2O2 or an H2O2-generating system did not effectively support isopropanol oxidation, indicating that isopropanol was not a substrate for the peroxidatic activity of catalase. The addition of azide by itself or H2O2 (in the presence of azide and NADPH) stimulated isopropanol oxidation, suggesting a pivotal, indirect role for H2O2 in the system. H2O2 may serve as a precursor of hydroxyl radicals. Accordingly, the oxidation of isopropanol was inhibited by hydroxyl radical scavenging agents, namely dimethylsulfoxide, mannitol, benzoate and 2-keto-4-thiomethylbutyric acid. Fe-EDTA, which is known to increase hydroxyl radical generation, stimulated the oxidation of isopropanol. The stimulation by Fe-EDTA was blocked by competing hydroxyl radical scavengers. Model hydroxyl radical generating systems such as the coupled oxidation of xanthine by xanthine oxidase, especially in the presence of Fe-EDTA, or the autoxidation of ascorbate in the presence of Fe-EDTA could also oxidize isopropanol. These results indicate that (a) rat liver microsomes are capable of oxidizing branched chain alcohols, and (b) hydroxyl radicals or a species with the oxidizing power of the hydroxyl radical, generated from microsomal electron transfer, may play a role in isopropanol oxidation.
UR - http://www.scopus.com/inward/record.url?scp=0019491539&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(81)80002-0
DO - 10.1016/S0006-2952(81)80002-0
M3 - Article
C2 - 6264923
AN - SCOPUS:0019491539
SN - 0006-2952
VL - 30
SP - 825
EP - 831
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 8
ER -