Phase I reactions oxidations

Plants. Metabolized by more than four types of phase I reaction (oxidation of the phenyl ring, oxidation of the methyl group, cleavage of the methyl ester and /V -dealkylation) to form eight metabolites at phase II, most of the metabolites are sugar conjugated... 

Among the phase I reactions, oxidation mediated by cytochrome P450 monooxygenases is the most important in insects. Resistance to insecticides caused by enhanced microsomal monooxygenase activities has been reported in numerous insects. 

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. 

Chemical transformations in the liver are greatly facilitated by the action of enzymes within the smooth endoplasmic reticulum of hepatocytes (often called the microsomal fraction). Phase I reactions (oxidation, reduction, and hydrolysis reactions) convert molecules into more polar forms that usually differ in biological activity from the parent form. Oxidation reactions occur primarily under the direction of a family of enzymes called P450- Non-specific esterases in the liver, plasma, and other sites catalyze the hydrolysis of esters, whereas amides are hydrolyzed in the liver. Protein drugs are often degraded by proteases and peptidases, which are abundant in many tissues, including the intestinal tract and plasma. Phase II reactions are conjugation reactions. 

In this scheme, a foreign compound, A, may foUow one of four main routes of metabolism to produce the product, C. In the first route i), A, an inactive compound, could be converted into an active compound, 5, by a Phase I reaction (oxidation, reduction, or hydrolysis). Examples of this type of reaction are hydroxylation of acetanahde, reduction of Prontosil, or hydrolysis of cyclophosphamide. The Compound, B, may be further metabolized by a Phase II... 

In general, phase I reactions, such as oxidation and ra-demethylation are delayed in the neonate but are fully operational at or above adult levels by 4-6 months of age in the full-term neonate [27a-30]. Conjugation pathways, such as glucuronidation, do not approach adult values until 3 or 4 years of age. Sulfation activity does appear to reach adult levels in early infancy. For drugs that are subject to metabolism by both pathways, such as acetaminophen, the efficient activity of the sulfation pathway allows infants and children to compensate for low glucuronidation ability... 

Phase I reactions (Figure 6.25) increase the polarity of the waste compound by oxidation or hydroxylation in a process which involves an electron transfer and... 

Metabolism and elimination are critical in determining medication blood level and longevity of action. Two main categories of metabolic reactions are phase I reactions and phase 11 reactions. Phase 1 reactions are oxidative reactions that involve the cytochrome P450 system, and phase 11 reactions are conjugative reactions. The rate-limiting step for most compounds occurs through phase I metabolism. 

The liver is the principal site of drug metabolism. Hepatic drug metabolism is usually classified into two distinct phases. Phase I reactions are oxidation, reduction or hydrolysis. One of the most important systems that catalyse oxidation are the haem-containing cytochrome P-450 enzymes. 

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

The chemical reactions involved in drug biotransformation are also classified as either phase I or phase II reactions.27,28 52 60 Phase I reactions consist of those using oxidation, reduction, or hydrolysis. Phase II reactions involve conjugation of the parent drug or the metabolite of a drug that was already metabolized using a phase I reaction. 

Phase I reactions include microsomal monooxygenations, cytosolic and mitochondrial oxidations, co-oxidations in the prostaglandin synthetase reaction, reductions, hydrolyses, and epoxide hydration. All of these reactions, with the exception of reductions, introduce polar groups to the molecule that, in most cases, can be conjugated during phase II metabolism. The major phase I reactions are summarized in Table 7.1. 

Hepatic metabolism accounts for the clearance of all benzodiazepines. The patterns and rates of metabolism depend on the individual drugs. Most benzodiazepines undergo microsomal oxidation (phase I reactions), including TV-dealkylation and aliphatic hydroxylation. The metabolites are subsequently conjugated (phase II reactions) to form glucuronides that are excreted in the urine. However, many phase I metabolites of benzodiazepines are pharmacologically active, with long half-lives. 

Phase I reactions are typically divided into three categories oxidation, reduction, and... 

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