TY - JOUR
T1 - Production of formaldehyde and acetone by hydroxyl-radical generating systems during the metabolism of tertiary butyl alcohol
AU - Cederbaum, Arthur I.
AU - Qureshi, Aziz
AU - Cohen, Gerald
N1 - Funding Information:
* This work was supported by USPHS Grants AA-03312, AA-01387 and AA-03508 (Alcohol Research Center) and by Research Career Development Award (AIC) 2KO2-AA-00003 from the National Institute of Alcohol Abuse and Alcoholism. t Author to whom all correspondence addressed. * Abbreviations: ‘OH, hydroxvl radical or a species with the oxidizing power of ihe hidroxyl radical; MelSO, dimethyl sulfoxide; KTBA. 2-keto-4-thiomethylbutyric acid; DETAPAC, diethylenetriaminepentaacetic acid; and 027, superoxide anion radical.
PY - 1983/12/1
Y1 - 1983/12/1
N2 - t-Butyl alcohol is not a substrate for alcohol dehydrogenase or for the peroxidatic activity of catalase and, therefore, it is used frequently as an example of a non-metabolizable alcohol. t-Butyl alcohol is, however, a scavenger of the hydroxyl radical. The current report demonstrates that t-butyl alcohol can be oxidized to formaldehyde plus acetone by hydroxyl radicals generated from four different systems. The systems studied were: (a) two chemical systems, namely, the iron catalyzed oxidation of ascorbic acid and the Fenton reaction between H2O2 and iron; (b) an enzymatic system, the coupled oxidation of xanthine by xanthine oxidase: and (c) a membrane-bound system. NADPH-dependent microsomal electron transfer. The oxidation of t-butyl alcohol appeared to be mediated by hydroxyl radicals, or by a species with the oxidizing power of the hydroxyl radical, because the production of formaldehyde plus acetone was (a) inhibited by competing scavengers of the hydroxyl radical; (b) stimulated by the addition of iron-EDTA; and (c) inhibited by catalase. The last observation suggests that H2O2 served as the precursor of the hydroxyl radical in all three systems. A possible mechanism is hydrogen abstraction to form the alkoxyl radical ((CH3)3-C-O), spontaneous fission of the alkoxyl radical to produce acetone and the methyl radical (CH3), interaction of the methyl radical with O2 to form the methyl peroxy radical (CH300), and decomposition of the later to formaldehyde. These results extend the alcohol oxidizing capacity of the microsomal alcohol oxidizing system to a tertiary alcohol. Since t-butyl alcohol is not a substrate for alcohol dehydrogenase or catalase, the ability of microsomes to oxidize t-butyl alcohol lends further support for a role for hydroxyl radicals in the microsomal alcohol oxidation system. In view of the production of formaldehyde, and the reactivity as well as further metabolism of this aldehyde, caution should be used in interpreting experiments in which t-butyl alcohol is used as a presumed "non-metabolizable" alcohol. t-Butyl alcohol may be a valuable probe for the detection of hydroxyl radicals in intact cells and in vivo.
AB - t-Butyl alcohol is not a substrate for alcohol dehydrogenase or for the peroxidatic activity of catalase and, therefore, it is used frequently as an example of a non-metabolizable alcohol. t-Butyl alcohol is, however, a scavenger of the hydroxyl radical. The current report demonstrates that t-butyl alcohol can be oxidized to formaldehyde plus acetone by hydroxyl radicals generated from four different systems. The systems studied were: (a) two chemical systems, namely, the iron catalyzed oxidation of ascorbic acid and the Fenton reaction between H2O2 and iron; (b) an enzymatic system, the coupled oxidation of xanthine by xanthine oxidase: and (c) a membrane-bound system. NADPH-dependent microsomal electron transfer. The oxidation of t-butyl alcohol appeared to be mediated by hydroxyl radicals, or by a species with the oxidizing power of the hydroxyl radical, because the production of formaldehyde plus acetone was (a) inhibited by competing scavengers of the hydroxyl radical; (b) stimulated by the addition of iron-EDTA; and (c) inhibited by catalase. The last observation suggests that H2O2 served as the precursor of the hydroxyl radical in all three systems. A possible mechanism is hydrogen abstraction to form the alkoxyl radical ((CH3)3-C-O), spontaneous fission of the alkoxyl radical to produce acetone and the methyl radical (CH3), interaction of the methyl radical with O2 to form the methyl peroxy radical (CH300), and decomposition of the later to formaldehyde. These results extend the alcohol oxidizing capacity of the microsomal alcohol oxidizing system to a tertiary alcohol. Since t-butyl alcohol is not a substrate for alcohol dehydrogenase or catalase, the ability of microsomes to oxidize t-butyl alcohol lends further support for a role for hydroxyl radicals in the microsomal alcohol oxidation system. In view of the production of formaldehyde, and the reactivity as well as further metabolism of this aldehyde, caution should be used in interpreting experiments in which t-butyl alcohol is used as a presumed "non-metabolizable" alcohol. t-Butyl alcohol may be a valuable probe for the detection of hydroxyl radicals in intact cells and in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0021049516&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(83)90297-6
DO - 10.1016/0006-2952(83)90297-6
M3 - Article
C2 - 6316986
AN - SCOPUS:0021049516
SN - 0006-2952
VL - 32
SP - 3517
EP - 3524
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 23
ER -