General Metabolism

Vacuolation (presence) Vac Metabolism, general condition Environmental pollutants Liver tissue 16-32... 

Some chemicals that strongly bind to biological receptors (ligands) can produce toxicity directly. However, most toxic chemicals are not intrinsically reactive and must be metabolized to reactive intermediates that often covalently bind to macromolecules (DNA, proteins, etc.), and, if present at a sufficient level, lead to toxicity. Metabolism generally serves to make lipophilic compounds more hydrophilic in order to facilitate excretion through the liver and into the bile for excretion into the feces or through the kidneys and into the urine. This process generally... 

Phase I metabolism generally introduces a functional group into a xenobiotic, which enables conjugation to an endogenous metabolite to occur during phase II metabolism. 

All of the vinca alkaloids exhibit very poor oral absorption and are given parenterally. Vinca alkaloids are predominantly excreted through the biliary tract or by hepatic metabolism. Generally, for patients with mild elevations in... 

When the transdermal penetration of a drug is inadequate to achieve and maintain a plasma concentration above the minimum therapeutic concentration required to produce the desired effect, a lipophilic prodrug that will be metabolized in the epidermis to the active drug could be used in the development of a controlled-release transdermal delivery system. This approach has been applied to estradiol esters (diacetate and valerate) which are rapidly converted by esterases in the skin tissue to estradiol (Chien et al, 1985). The prodrug serves to increase the transdermal bioavailability of the active drug to which it is converted by metabolism (generally ester hydrolysis) during the percutaneous absorption process. 

Chemicals absorbed into the body are metabolized by a wide range of enzymes to more water soluble forms that can be eliminated from the body. Metabolism generally takes place in two phases. In Phase I, a polar functional group is introduced into the molecule. In Phase II, the functional group introduced is combined with an endogenous compound to form a water soluble species that can be eliminated from the body. 

Considerable efforts have gone into the SAR studies on tetrahydrocarbazolones. F irst, substituting the indole nucleus at C6 (e.g., 151,152), a potential site of metabolism, generally reduces potency, with the exception of the 6-F derivative (150). Second, substitution at the 9-position is well tolerated (e.g., 153, 154), but some long-chain lipophilic substituents reduce activity (e.g., 155). Third, the carbonyl function in this series is critical to potent 5-HT, antagonist activity. The corresponding alcohols (156,157) and the tetrahy-drocarbozole (158) are less potent than the... 

Many proteins are regulated by molecules which bind somewhere other than at the active site and either inerease or decrease protein activity. These allosteric ejfectors are often quite specific and may have either a positive or negative effect upon protein activity. C ass cdX feedback inhibition cycles in metabolism generally involve heterotropic allostery, in which a molecule produced near the end of a metabolic pathway acts as an allosteric effector to regulate a protein active earlier in the same pathway. Because of the need for very precise control of the energy charge of the cell, ATP and ADP serve as allosteric effectors for several of the proteins of glucose metabolism. Protons and ions act as allosteric effectors in many... 

This chapter emphasized palmitic acid, its physical, chemical and structural features as pertaining to its functional characteristics, occrtrrence and percent distribution in plants, algae, fimgus, human and animal tissues. The antimicrobial mechanisms of action, metabolism, general biochemisby and health implications of palmitic acid provide insight into the versatile... 

Most organic compounds undergo metabolic change in the body (see Williams, 1959) and from the point of view of biliary excretion, this process is important because metabolism generally increases the siae of the administered moletsule and also often introduces an anionic group into the structure. This may, therefore, result in the production of a metabolite with tlie necessary chemical factors of molecular. size and polarity for extensive biliary excretion. 

A. Protein Hydrolyzing Enzymes. B. Enzymes in Amino Acid Metabolism (General). C. Specific Amino Acid Enzymes. D. Peptide Bond Synthesis. E. Enzymes in Urea Synthesis. F Ammonia Liberating Enzymes. G. Nitrate Metabolism. 

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