Biotransformation reactions oxidative

Biotransformation reactions can be classified as phase 1 and phase 11. In phase 1 reactions, dmgs are converted to product by processes of functionalization, including oxidation, reduction, dealkylation, and hydrolysis. Phase 11 or synthetic reactions involve coupling the dmg or its polar metaboHte to endogenous substrates and include methylation, acetylation, and glucuronidation (Table 1). 

See also Biotransformations Microbial oxidations Microbial reductions applications of, 76 396-399 biocatalyst selection in, 76 404-409 biocatalysts in, 76 409-414 for drug metabolite production, 76 398-399 further advances in, 76 414 in hydrolysis, 76 400-401 multiphase reactions in, 777 412-414 scale-up of, 76 414 systematic studies of, 76 398 technique overview for, 76 403-414 timing of substrate additions in, 76 411-412 uses for, 777 400-403 Microbial waxes, 26 203 Microbiocides, triorganotins as, 24 817 Microbiological culture media, agar in, 73 68... 

Although UGTs catalyze only glucuronic acid conjugation, CYPs catalyze a variety of oxidative reactions. Oxidative biotransformations include aromatic and side chain hydroxylation, N-, O-, S-dealkylation, N-oxidation, sulfoxidation, N-hydroxylation, deamination, dehalogenation and desulfation. The majority of these reactions require the formation of radical species this is usually the rate-determining step for the reactivity process [28]. Hence, reactivity contributions are computed for CYPs, but a different computation is performed with the UGT enzyme (as described in Section 12.4.2). 

Hydrolysis of phthalate diesters to the respective monoesters appears to be the first and the major biotransformation reaction in all of these species, but subsequent oxidative metabolism also may occur. 

In general, biotransformation reactions are beneficial in that they facilitate the elimination of xenobiotics from pulmonary tissues. Sometimes, however, the enzymes convert a harmless substance into a reactive form. For example, CYP-mediated oxidation often results in the generation of more reactive intermediates. Thus, many compounds that elicit toxic injury to the lung are not intrinsically pneumotoxic but cause damage to target cells following metabolic activation. A classic example of this is the activation of benzo(a)pyrene, which is a constituent of tobacco smoke and combustion products, and is... 

Phase 1 reactions Oxidative reactions involving N- and O-dealkylation, aliphatic and aromatic hydroxylation, N- and S-oxidation, deamination. Phase 2 reactions Biotransformation reactions involving glucuronization, sulphation, acetylation. 

Grape compounds which can enter the yeast cell either by diffusion of the undissociated lipophilic molecule or by carrier-mediated transport of the charged molecule across the cell membrane are potentially subject to biochemical transformations by enzymatic functions. A variety of biotransformation reactions of grape compounds that have flavour significance are known. One of the earlier studied biotransformations in yeast relates to the formation of volatile phenols from phenolic acids (Thurston and Tubb 1981). Grapes contain hydroxycinnamic acids, which are non-oxidatively decarboxylated by phenyl acryl decarboxylase to the vinyl phenols (Chatonnet et al. 1993 Clausen et al. 1994). 

The superfamily of P450 cytochrome enzymes is one of the most sophisticated catalysts of drug biotransformation reactions. It represents up to 25% of the total microsomal proteins, and over 50 cytochromes P450 are expressed by human beings. Cytochromes P450 catalyze a ivide variety of oxidative and reductive reactions, and react with chemically diverse substrates. Despite the large amount of information on the functional role of these enzymes combined with the knowledge of their three-dimensional structure, elucidation of cytochrome inhibition, induction, isoform selectivity, rate and position of metabolism all still remain incomplete [6]. 

Species variation has been observed in many oxidative biotransformation reactions. For example, metabolism of amphetamine occurs by two main pathways oxidative deamination or aromatic hydroxylation. In the human, rabbit, and guinea pig. oxidative deamination appears to be the predominant pathway in the rat. aromatic hydroxylation appears to be the more important route. Phenytoin is another drug that shows markeii species differences in metabolism. In the human, phenytoin undergoes aromatic oxidation to yield primarily (5K-)-/r-hydioxyphenytoin in the dog. oxidation occurs to give mainly (If)(-1-)-iM-hydroxyphenyt-oin. There is a dramatic difference not only in the pasition (i.e.. meta or para) of aromatic hydroxylation but also in which of the two phenyl rings (at C-S of phenytoin) undergoes aromatic oxidation. 

TNT is readily absorbed through skin, especially when skin is moist. It is excreted in urine more than in feces some is found in bile. The major biotransformation reaction is nitroreduction and, to a lesser extent, oxidation. The main metabolite formed by nitroreduction seems to be 4-amino-2,6-dinitrotoluene (4-ADNT). Other metabolites include 2-amino-4,6-dinitrotoluene (2-ADNT), 2,4-diamino-6-nitrotoluene, and 2,6-diamino-4-nitrotoluene. The metabolites are excreted in the urine as glucuronide conjugates and in the free form. Ring oxidation products of TNT such as trinitrobenzylalcohol, trinitrobenzoic acid, and simultaneous oxidation and reduction metabolites such as 2,6-dinitro-4-amino-benzylalcohol and 2,6-dinitro-4-amino-m-cresol are of less importance. Untransformed TNT is also excreted in the urine. ADNT and TNT concentrations were found in workers in explosives factories. 4-ADNT excretion was reported to be complete within 3M days after exposure. However, another study reported detectable urine concentration of ADNT in explosives workers even after 17 days away from the workplace. 

Of the Phase I reactions, oxidative biotransformations are by far the most common. These reactions are carried out by several oxidative enzyme systems, the most predominant of which is the CYP superfamily of enzymes. Additional oxidative enzymes include FMO, xanthine oxidase, aldehyde oxidase, alcohol and aldehyde dehydrogenases monoamine oxidases, and various peroxidases. Determining the enzyme(s) employed to biotransform any particular substrate will depend on the substrates chemical and physical characteristics as well as functional substituents. This chapter does not describe in detail the mechanism of these various enzymes however, it does illustrate the product(s) (i.e., metabolites) produced by each reaction. 

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