Metabolism scheme

Levels of Significant Exposure to Acrylonitrile - Inhalation 2-2 Levels of Significant Exposure to Acrylonitrile—Oral 2-3 Proposed Metabolic Scheme for Acrylonitrole 2-4 Existing Information on Health Effects of Acrylonitrile 5-1 Frequency of Sites with Acrylonitrile Contamination... 

Acrolein is a metabolite of allyl alcohol and cyclophosphamide, and these compounds should be considered in acrolein metabolism schemes (Beauchamp et al. 1985 Cohen et al. 1992). Allyl alcohol in the presence of NADPH and liver or lung microsomes degrades to acrolein, acrylic acid, and glycidol (Figure 10.1). 

Figure 19.1 Metabolic scheme for famphur in mammals. (Adapted from Gatterdam, P.E., L.A. Wozniak, M.W.

Proposed Metabolic Scheme for Endrin in Mammals 2-4 Existing Information on Health Effects of Endrin... 

From the standpoint of biochemical genetics and the genetotrophic principle, however, it seems likely that partial genetic blocks (which impose increased demands) may happen anywhere in the entire metabolic scheme in what may be assumed, without further evidence, to be in a random fashion. If this be the case, any and every nutritional need may be represented among those which are observed to be augmented. 

The herbicide alachlor (4.146, Fig. 4.7) also displayed species-dependent toxicity, since it induced nasal tumors in rats but not in mice. Its metabolic scheme in rats and mice (Fig. 4.7) shows that alachlor can be transformed into 2,6-diethylaniline (4.149) by two different pathways, one of which proceeds via formation of 4.147. The other pathway implies glutathione (GSH) conjugation, followed by /3-lyase-mediated liberation of the thiol, followed by S-methylation to produce the methylsulfide 4.148. The two secondary amides 4.147 and 4.148 were hydrolyzed by microsomal arylamidases, but alachlor itself was not a substrate for this enzyme. The hydrolytic product 2,6-diethylaniline (4.149) was oxidized in nasal tissues to the electrophilic quinonimine metabolite 4.150, which can bind covalently to proteins. Aryl-... 

Fig. 9.10. Partial metabolic scheme of tris(2-methylphenyl) phosphate (9.44) showing hydrolysis to the diester 9.45, the monoester, and phosphate. Also shown is a reaction of oxidation to the hydroxymethyl analogue 9.46, followed by cyclization to the toxic cyclic phosphate 9.47...

Fig. 9.13. Hypothetical metabolic scheme of salithion (9.69), based on its metabolism in rats... 

Flupyrazofos (9.75) is an insecticide whose relatively simple metabolic scheme appears quite informative. Indeed, rat liver microsomes formed the oxon analogue as the only detectable primary metabolite [150], The latter then underwent chemical hydrolysis to the dephosphorylated phenol with a tm value of ca. 50 min at pH 7.4 and 37°. In rat liver microsomes, the phenol appeared to be produced exclusively from flupyrazofos oxon, indicating the resistance of flupyrazofos toward chemical hydrolysis. 

Fig. 10.8. Simplified and partial metabolic scheme of benzene. Cytochrome P450 mediated oxidation (Reaction a) yields benzene oxide (10.1), which produces phenol (10.14) by isomerization (Reaction c) and 1,2-dihydro-1,2-dihydroxybenzene (10.13) by epoxide hydrolase catalyzed hydration (Reaction d). Direct formation of phenol also occurs (Reaction b). Phenol...

In vitro studies on rat liver preparations confirmed the postulated metabolic pathway of nonenzymatic hydrolysis of the oxime 11.69 to the ketone 11.70, followed by enzymatic reduction to 11.71, hydroxylation to diols, and glucuronidation. Clearly, the first step in this metabolic scheme is the nearly quantitative hydrolysis of the oxime to the ketone. 

Fig. 11.12. Metabolic scheme for reaction of benzyl cyanide (11.80) to mandelonitrile (11.81) as a crossroads to benzoic acid (11.83) via oxidative denitrilation, and to mandelic acid (11.82) as a minor metabolite produced by hydrolysis of the CN group [118][122]...

Levels of Significant Exposure to Heptachlor and Heptachlor Epoxide - Oral 2-2 Metabolic Scheme for Heptachlor in Rats ... 

Levels of Significant Exposure to 1,2-Diphenylhydrazine-Oral 2-2 Metabolic Scheme of 1,2-Diphenylhydrazine 2-3 Existing Information on Health Effects of 1, 2-Diphenylhydrazine 5-1 Frequency Of NPE Sites with 1.2-Diphenylhydrazine Contamination... 

A form of regulation in a metabolic pathway in which an end product (or even an intermediate in the pathway) binds to and inhibits an enzyme which catalyzes an earlier reaction in that same pathway. For example, consider the metabolic scheme A B C Din which the steps are respectively catalyzed by the enzymes Ei, E2, and E3. Feedback inhibition would be seen when elevated concentrations of D (or C) inhibited Ei. 

So, by competing with natural pyrines and pyrimidines in metabolic schemes, they interfere with the synthesis of nucleic acids, thus being included in place of ordinary metabolites. This leads to the formation of cellular products, which cannot function normally. Thus, cellular processes of division and multiplication are disrupted. 

Leisola et al. (15) have studied the metabolism of veratryl alcohol by ligninolytic cultures of P. chrysosporium. From studies with 14C ring labeled compounds, the metabolic scheme depicted in Figure 4 was postulated. 

The metabolism of ethylbenzene in humans occurs along one major pathway which is oxidation at the a-carbon, yielding 1-phenylethanol (also called a-methylbenzyl alcohol) as the primary product. A metabolic scheme is presented in Figure 1. The a-carbon of ethylbenzene is a prochiral centre and hydroxylation thus yields a chiral product. The issue of stereoselectivity has been addressed in animal studies (see Section 4.1.2). 

Fig. 3 Speculative metabolic schemes of the main pathways in carbohydrate metabolism in N. ovalis Abbreviations AcCoA, acetyl-CoA, Cl, complex I, Citr, citrate, FRD, fumarate reductase, FUM, fumarate, Hyd, hydrogenase, a-KG, a-ketoglutarate, MAL, malate, OXAC, oxaloacetate, PDH, pyruvate dehydrogenase, PEP, phosphoenolpyruvate carboxyk-inase, PYR, pyruvate, RQ, rhodoquinone, SUCC, succinate, SUCC-CoA, succinyl-CoA...

Metabolism may involve many sequential steps, not just one phase 1 followed by one phase 2 reaction. Phase 1 reactions can sometimes follow phase 2 reactions, one molecule can undergo several phase 1 reactions, and cyclical or reversible metabolic schemes may operate. Thus, further metabolic transformations, sometimes termed phase 3 reactions, can convert a detoxified metabolite into a toxic product (see hexachlorobutadiene and hydroquinone). 

Figure 1. Proposed metabolic scheme for the formation of mercapturic acid metabolites of 1,2-dichloropropane in the rat...

Figure 20-8 Perspective of the metabolic scheme whereby carbohydrates, fats, and proteins in foodstuffs are oxidized to C02, showing the link between glycolysis, the citric acid cycle, and oxidative phosphorylation...

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