Metabolism enzymatic

Fig. 18 Diagrammatic sketch indicating sites along the GIT where drug may be chemically altered or enzymatically metabolized. (Copyright 2000 Saguaro Technical Press, Inc., used with permission.)...

Hardeland, R., Poeggeler, B., Behrmann, G. 8r Fuhrberg, B. (1996). Enzymatic and non-enzymatic metabolism of methoxyindoles. In ed. Hardeland, R. Metabolism and Cellular Dynamics of Indoles. (Goettingen University of Goettingen)... 

At low substrate concentrations, the passage through the cytoplasmic membrane, rather than enzymatic metabolism inside the cell is the major... 

Enzymatic-metabolic activation (in part unknown)/phenobarbital-like promotion Hepatic enzyme induction, thyroid enzyme inhibition/axazepam, amobarbital, sulphonamides, thioureas Gastric secretory suppression, gastric atrophy induction (climetidine, omeprazole, butachlor... 

Endothelial permeability Transporter proteins Enzymatic/metabolic activity Disease Tissue composition (drug sequestration) Dose size/volume Conformation Chemical stability Enzymatic stability... 

The inactivation of histamine is achieved both by enzymatic metabolism of the amine and by transport processes that reduce the concentration of the compound in the region of its receptors. Histamine metabolism occurs primarily through two pathways (Fig. 38.1). The most important of these involves histamine N-methyltransferase, which catalyzes the transfer of a... 

The enzymatic metabolism of the pre-carcinogen, i.e., conversion to an electrophile and its reaction with nucleic acid. 

In man, BH4 is degraded either nonenzymatically by side-chain cleavage to pterin or is enzymatically metabolized in the gastrointestinal tract to become a lumazine [2]. Pterin and dihydropterin are converted by xanthine dehydrogenase to isoxanthopterin and xanthopterin, respectively [3,4]. It is assumed, however, that most of the ingested BH4 is used as a cofactor (mainly for PAH in the liver) and is catabolized to nonfluorescing compounds it may even be degraded to C02 and ammonia. 

Physiological factors affecting absorption, for example, gastrointestinal (Gl) transit time, gastric emptying time, Gl content, surface area, pH, enzymatic metabolism, and site-speciLc absorption... 

The likelihood that a xenobiotic species will undergo enzymatic metabolism in the body depends on the chemical nature of the species. Compounds with a high degree of polarity, such as relatively ionizable carboxylic acids, are less likely to enter the body system and, when they do, tend to be quickly excreted. Therefore, such compounds are unavailable, or available for only a short time, for enzymatic metabolism. Volatile compounds, such as dichloromethane or diethylether, are... 

A prodmg is a pharmacacologically inactive compound which undergoes chemical or enzymatic metabolism to the active. Some of the early pharmaceuticals were found to be prodrugs and this finding has led to the subsequent introduction of the metabolite itself into therapy, particularly in cases where the active metabolite is less toxic or has fewer side-effects than the parent prodmg. The administration of the active metabolite may also reduce variability in clinical response between individuals due to differences in pharmacogenetics. 

Figure 16.4 Schematic illustration of the implantable glucose monitor under development at Synthetic Blood International. The biosensing mechanism is based on the glucose oxidase-catalyzed oxidation of glucose drawn from tissue fluids. After the enzymatic metabolism, the ratio of hydrogen peroxide to oxygen is detected and expressed by a change in electric current. This signal is transmitted to the receiver outside the body...

To prove the above hypothesis of precocene mode of action, it was required to synthesize the corresponding 3,4-epoxyprecocenes and to study its chemical reactivity. When this was accomplished in two different laboratories (16,18) the lability of these epoxides towards nucleophilic or electrophilic attack was confirmed.In each case the chemical hydrolysis of these compounds gave the same isomer ratio of diols observed in the enzymatic metabolic process. 

Both linamarin and amygdalin are toxic compounds because they are metabolized to cyanohydrins, which are hydrolyzed to carbonyl compounds and toxic HCN gas. This second step is merely the reconversion of a cyanohydrin to a carbonyl compound, a process that occurs with base in reactions run in the laboratoiy (Section 21.9A). If cassava root is processed with care, linamarin is enzymatically metabolized by this reaction sequence and the toxic HCN is released before the root is ingested, making it safe to eat. 

Considering the courses of the chemical reductions of the A -3-ketone system, it is not surprising to find that the enzymatic metabolic reductions are very similar in behavior to the chemical reductions. Thus, reduction of the 4,5-double bond gives rise to a mixture of 5a- and 5/8-steroids and the ratio depends on the nature of substituents in the molecule. Without an 11-oxygen function the ratio of 5/3- to 5a-dihydro derivatives was found to be 1 1 [342] to 2 1 [301]. In the presence of an 11-oxygen function (ll-hydroxy [343,344] and 11-keto [345]) the ratio of 5a- to 5/3-reduced metabolites was 4 1 or 5 1. 

The enzymatic metabolic defect is mainly restricted to the erythrocytes or bone marrow. Two distinct clinical pictures can be differentiated congenital erythropoietic porphyria (CEP) and erythropoietic protoporphyria (EPP) (W Kosenow et at, 1953 LA. Magnus et at, 1961). From a hepatological point of view, only EPP is important, (s. tab. 31.12)... 

Brodie, B.B., Gillette, J.R. LaDu, B.N. (1958) Enzymatic metabolism of drugs and other foreign compounds. Annual Review of Biochemistry, 27, 427-454. 

An inhibiting chemical slows the enzymatic metabolism of a toxic chemical. In this instance, if the uptaken chemical itself is the toxin, inhibition will slow the metabolism and intensify its action. If the metabolite of the absorbed xenobiotic is the toxic agent, inhibition will decrease the toxic affect. Vinyl chloride uptake in rats results in the lowering of cytochrome P450 and a corresponding loss of ability to metabolize other xenobiotics. Other inhibitors include diethyl maleate, which inhibits glutathione s-transferase and 1-aminobenzotriazole, which inhibits P450. 

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