Oxidation metabolism, principles

The bioactive PGs are further metabolized to decomposition products that are subsequently eliminated from the body by excretion in urine. This metabo-lization increases the structural multiplicity of the prostanoids. It should be emphasized that some of the metabolization products may still be bioactive. The decomposition pathways for various prostanoids are different but there are common principles for prostanoid metabolization (i) oxidation of the OH-group at C-15, forming the corresponding keto derivatives (ii) p-oxidation of the carboxyl terminus, forming the di-nor prostaglandins and (iii) co-oxidation of the... 

The close structural resemblance of anandamide and arachi-donic acid has prompted a series of biochemical experiments to test the possibility that anandamide serves as a substrate for enzymes that metabolize the polyunsaturated fatty acid. These experiments have considerable interest because, in principle, oxidative metabolism may modify the biological properties of anandamide—for example, change its affinity for cannabinoid receptors. 

Extensive metabolic work continues with the pyrrolizidine alkaloids many of which are known toxic principles of plants responsible for conditions such as irreversible hemorrhagic liver necrosis, megalocytosis, and cancer. Considerable interest remains in the metabolism of pyrrolizidine alkaloids and their A-oxides to metabolic pyrroles thought to participate in molecular events associated with the above-mentioned toxicities. The chemistry and pharmacological properties of the pyrrolizidine alkaloids is authoritatively discussed by Wrobel in Volume 26 of this treatise. 

A principle in metabolic regulation that allows one to identify the inhibited step within a metabolic pathway as that reaction for which the concentrations of reactants and products rise and fall, respectively, from their steady-state values when an inhibitor is introduced. In the context of the electron transfer chain, the crossover-point refers to that reaction step demarking the transition from more reduced to more oxidized respiratory enzymes. 

As in the case of propachlor mercapturic acid sulfoxide, the biological significance of xenobiotic mercapturic acids that contain oxidized sulfur is not known. Casida et al. (39) have reported that sulfoxidation of some thiocarbamate herbicides is a beneficial step in the detoxication process. However, cysteine conjugates can exhibit adverse biological activities. Smith (40) has reviewed work on the metabolism of the toxic principle in kale and has shown that C-S lyase action on S-methylcysteine sulfoxide produces the toxic principle. Virtanen ( ) has reviewed the processes in other plants that lead to the production of compounds with biological activity from -substituted cysteine sulfoxides. 

We begin Part II with a discussion of the basic energetic principles that govern all metabolism (Chapter 13). We then consider the major catabolic pathways by which cells obtain energy from the oxidation of various fuels (Chapters 14 through 19). Chapter 19 is the pivotal point of our discussion of metabolism it concerns... 

The principles of oxidation-reduction energetics described above apply to the many metabolic reactions that involve electron transfers. For example, in many organisms, the oxidation of glucose supplies energy for the production of ATP. The complete oxidation of glucose ... 

Figure 7.9 The metabolism of halothane and its proposed involvement in liver toxicity. Pathway I (oxidative) and pathway 2 (reductive) are both catalyzed by cytochrome P450. Source J. A. Timbrell (1991), Principles of Biochemical Toxicology, 2nd ed. London Taylor Francis.

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