Alcohol cytochrome

Oxidation of primary alcohols leads to aldehydes and oxidation of secondary alcohols leads to ketones. This oxidation also involves the loss of two hydrogen atoms. However, unlike the oxidations discussed so far in this chapter that are mediated almost exclusively by cytochromes P450, the major enzyme involved in the oxidation of ethanol is ALD (discussed earlier in this chapter) (74). Although ALD is the major enzyme involved in the oxidation of ethanol and most other low molecular-mass alcohols, cytochromes P450, especially 2E1, can also oxidize ethanol and this enzyme is induced in alcoholics. Although comprehensive studies have not been published, it appears that cytochromes P450 are often the major enzymes involved in the oxidation of higher molecular mass alcohols. 

In addition to the conversion of unactivated alkanes to alcohols, cytochrome P450 hemes transform alkenes to epoxides, arenes to phenols, and sulfides to sulfoxides to sulfones. Furthermore, they are involved in the biosynthesis and biodegradation of endogenous compounds such as steroids, fatty acids, prostaglandins and leukotrienes. Under anaerobic conditions, P450 will reductively dehalogenate haloalkanes to the corresponding alkanes. 

The Use of Primary Kinetic Isotope Effects to Probe the Mechanism of Aliphatic Hydroxylation by Iron(III) Porphyrins One reaction that is uncommon in organic chemistry but is common in biological systems in the hydroxylation of alkanes to form alcohols. Cytochrome P-450, a heme containing enzyme, catalyzes this reaction. Large primary isotope effects are found, as well as an absence of carbocation-like skeletal rearrangements and loss of stereochemistry. These observations led researchers to conclude that a radical cage mechanism is operative. 

Asai (21) proposed that the primary Kombucha bacterium, Acetobacter, initially oxidizes ethanol to acetaldehyde and then to acetic acid. Ethanol is oxidized to acetaldehyde by alcohol-cytochrome-553 reductase and the resulting electrons are successively delivered to the heme iron of cytochrome-553. The acetaldehyde thus formed is oxidized further by coenzyme-independent aldehyde dehydrogenase or by NADP-dependent aldehyde dehydrogenase. Observations on alcohol dehydrogenase have been made by Ameyama and Adachi (22) who... 

Cu-+ Peroxidase Cytochrome oxidase Nicotinamide adenine dinucleotide (NAD) Hydride ion (H ) Alcohol dehydrogenase... 

Shi J, Hui L, Xu Y, et al Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat 19 459 60, 2002 Shinderman M, Maxwell S, Brawand-Arney M, etal Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Drug Alcohol Dependence 69 205-211, 2003... 

Analysis of reaction mixtures for 1-propanol and 2-propanol following incubation of NDPA with various rat liver fractions in the presence of an NADPH-generating system is shown in Table I ( ). Presence of microsomes leads to production of both alcohols, but there was no propanol formed with either the soluble enzyme fraction or with microsomes incubated with SKF-525A (an inhibitor of cytochrome P450-dependent oxidations). The combined yield of propanols from 280 ymoles of NDPA was 6.1 ymoles and 28.5 ymoles for the microsomal pellet and the 9000 g supernatant respectively. The difference in the ratio of 1- to 2-propanol in the two rat liver fractions may be due to differences in the chemical composition of the reaction mixtures (2) Subsequent experiments have shown that these ratios are quite reproducible. For comparison, Table I also shows formation of propanols following base catalyzed decomposition of N-propyl-N-nitrosourea. As expected (10,11), both propanol isomers were formed, the total yield in this case being almost quantitative. 

Albano, E., Tomasi, A., Persson, J.O., Terelius, Y., Goria-Gatti, L., Ingelman-Sundberg, M. and Dianzani, M.U. (1991). Role of ethanol inducible cytochrome P-450 (P450IIE1) in catalysing the free radical activation of aliphatic alcohols. Biochem. Pharmacol. 41, 1895-1902. 

Alcohol dehydrogenases found in certain microorganisms utilize a pyrroloquino-line quinone (PQQ) or flavin cofactor to pass electrons released upon oxidation of alcohols to the heme electron-acceptor protein, cytochrome c. These membrane-associated alcohol dehydrogenases form part of a respiratory chain, and the energy from fuel oxidation therefore contributes to generation of a proton gradient across... 

Materials. Microspherical PGG glucan (Adjuvax, Alpha-Beta Technology, Worcester, MA) was prepared from Saccharomyces cereviseae strain R4 cells (11). Zymosan, cytochrome c (cyt c), bovine serum albumin (BSA), yeast alcohol dehydrogenase (ADH), Complete Freunds Adjuvant (CFA) and Incomplete Freunds Adjuvant (IFA) were purchased from Sigma Chemical Co. (St. Louis, MO). 

Kessova, I.G., Leo, M.A., and Lieber, C.S. 2001. Effect of beta-carotene on hepatic cytochrome P-450 in ethanol-fed rats. Alcohol Clin Exp Res 25 1368-1372. 

In the field of enzyme catalysis, heme-proteins such as cytochrome P450, for example, exhibit both types of 0-0 bond cleavages in organic hydroperoxides and peroxy acids (178). Heterolytic cleavage of HOOH/ROOH yields H20 or the corresponding alcohol, ROH and a ferryl-oxo intermediate (Scheme 4). Homolytic 0-0 bond cleavage results in the formation of a hydroxyl (HO ) or an alkoxyl (RO ) radical and an iron-bound hydroxyl radical. 

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