Aliphatic metabolic pathways

The NHase responsible for aldoxime metabolism from the i -pyridine-3-aldoxime-degrading bacterium, Rhodococcus sp. strain YH3-3, was purified and characterized. Addition of cobalt ion was necessary for the formation of enzyme. The native enzyme had a Mr of 130000 and consisted of two subunits (a-subunit, 27 100 (3-subunit, 34500). The enzyme contained approximately 2 mol cobalt per mol enzyme. The enzyme had a wide substrate specificity it acted on aliphatic saturated and unsaturated as well as aromatic nitriles. The N-terminus of the (3-subunit showed good sequence similarities with those of other NHases. Thus, this NHase is part of the metabolic pathway for aldoximes in microorganisms. 

Acetylation of xenobiotic primary amine groups is a common metabolic pathway, whereas acetylation of xenobiotic hydroxyl and sulfhydryl groups is not. Primary aliphatic and aromatic amines, sulfonamides, hydrazines, and hydrazides are readily N-acetylated in vivo, and the reaction is catalyzed by various acetyl CoA N-acetyltransferases, commonly called N-acetyltransferases, as shown in Figure 16. 

S-adenosyl-L-methionine (SAM)-dependent methyl-ation was briefly discussed under Thiomethylation (see Figure 14). Other functional groups that are methylated by this mechanism include aliphatic and aromatic amines, N-heterocyclics, monophenols, and polyphenols. The most important enzymes involved in these methylation reactions with xenobiotics are catechol O-methyltransferase, histamine N-methylt-ransferase, and indolethylamine N-methyltransferase - each catalyzes the transfer of a methyl group from SAM to phenolic or amine substrates (O- and N-methyltransferases, respectively). Methylation is not a quantitatively important metabolic pathway for xenobiotics, but it is an important pathway in the intermediary metabolism of both N- and O-contain-ing catechol and amine endobiotics. 

Distribution, Storage and Excretion. Hydrocarbons in each of the aliphatic and aromatic fractions are expected to be distributed throughout tissues and organs following absorption. Preferential distribution to fatty tissues occurs especially with aliphatic hydrocarbons. Ingested or inhaled volatile aliphatic and aromatic hydrocarbons in the HC5-EC8 and EC5-EC9 fractions can be eliminated in exhaled breath as unchanged parent compound. Metabolic elimination of aromatic hydrocarbons in each EC fraction predominately occurs via oxidative metabolic pathways involving... 

Naphthalene is toxic to the lung and these metabolic pathways are important in this toxicity (see below). There are many types of substrates for glutathione conjugation including aromatic, aliphatic, heterocyclic and alicyclic epoxides, halogenated aliphatic and aromatic... 

Secondary and primary amines also undergo N-oxygenation and the first isolable metabolites are hydroxylamines (reactions 3-A and 4-A, respectively). Again, reversibility is documented (reactions 3-B and 4-B). These compounds can be aliphatic or aromatic amines, and the same metabolic pathway occurs in secondary and primary amides (i.e., R = acyl), whereas tertiary amides seem to be resistant to N-oxygenation. The oxidation of secondary amines and amides usually stops at the hydroxylamine/hydroxylamide level, but formation of short-lived nitroxides (not shown) has been reported. 

Various studies regarding the biotransformation of xenobiotic ketones have established that ketone reduction is an important metabolic pathway in mammalian tissue. Because carbonyl compounds are lipophilic and may be retained in tissues, their reduction to the hydrophilic alcohols and subsequent conjugation are critical to their elimination. Although ketone reductases may be closely related to the alcohol dehydrogenases, they have distinctly different properties and use NADPH as the cofactor. The metabolism of xenobiotic ketones to free alcohols or conjugated alcohols has been demonstrated for aromatic, aliphatic, alicyclic, and unsaturated ketones (e.g., naltrexone, naloxone, hydromorphone, and daunorubicin). The carbonyl reductases are distinguished by the stereospecificity of their alcohol metabolites. 

A number of Pseudomonas strains can accumulate PHAs from a variety of aromatic hydrocarbons. In many strains, the level of PHA accumulation is dependent on the side chain length of the phenylalkanoic acid provided for growth. The PHA accumulated from styrene and phenylacetic acid was composed of aliphatic monomers only. The PHA accumulated from any one of the phenylalkanoic acids with five carbons or more in their side chain was almost identical for all strains with the PHA composed of both aromatic and aliphatic monomers. The predominant monomers accumulated were 3-hydroxyphenylvaleric acid and 3-hydro3g henylhexanoic acid. The addition of the metabolic pathway inhibitors acrylic acid and 2-bromooctanoic acid resulted in decreased levels of PHA from phenylacetic acid, suggesting a... 

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