Chemical factors, affecting metabolism

Hodgson E. Chemical and environmental factors affecting metabolism of xenobiotics. In Hodgson E, Levi PE, eds. Introduction to Biochemical Toxicology. 2nd ed. Connecticut Appleton-Lange, 1994. Jakoby WE, ed. Enzymatic Basis of Detoxication. New York Academic Press, 1980. 

Hodgson, E. (1994). Chemical and environmental factors affecting metabolism of xeno-biotics. In Introduction to Biochemical Toxicology (Hodgson. L. and Levi. P. E.. eds). eh. 7, pp. 153-175. Appleton and Lange. Norwalk, CT. 

In this part we deal with the major chemical and physical factors affecting insect cell growth, baculovirus replication and product expression. The issues addressed are cell line selection for product expression, baculovirus-cell interactions and impact of differences in metabolic requirements of infected and non-infected cells in overall productivity. 

Factors affecting absorption, distribution, binding, metabolism, and elimination of chemicals... 

In contrast to penetrating radiation, which passes through tissue in a weU-known manner, or even with the more complex situations arising fiom nonuniform distributions of internally deposited radionuclides, dosimetry of chemicals is far more difficult. Factors requiring consider ation in chemical dosimetry include the type of chemical under consideration, dose, duration of exposure, route of administration, aU possible metabolic pathways, capacity of the chemical to affect its own metabolism, pharmacokinetics, rate of excretion, and dose to the biological target at sites of tumor formation (which may vary depending on the route of administration). 

There are many factors, both chemical and biological, which affect the disposition of xenobiotics. Chemical factors include size and structure, pKa, chirality, and lipophilicity. Biological factors include species, sex and strain, genetic factors, hormonal influences, disease and pathological conditions, age, stress, diet, dose, enzyme induction and inhibition, and tissue and organ specificity. All of these factors can affect the toxicity of a chemical by changing its disposition, especially its metabolism. 

Chemical factors. Lipophilicity, polarity, and size of a molecule are all important in determining absorption, distribution, metabolism, and excretion of the chemical and hence its toxicity. The chirality of a molecule may affect its absorption, distribution, excretion, and the route of metabolism or extent to which it is metabolized and hence its toxicity. Planarity may affect the interaction with a receptor. 

In solution, the anthocyanins actually might exist in equilibrium with essentially four molecular forms - the flavylium cation, the quinoidal base, the hemiacetal base and chalcone [19]. The relative amounts of the four structure forms depends on both the pH and the difference in structure of the anthocyanins [20-22], Generally, anthocyanins exist primarily as the stable flavylium cation above pH 2. This uniqueness in the chemical structure is one of the important key factors affecting their absorption, metabolism, bioavailability and, consequently, the biological responses of the human body to anthocyanins. 

This chapter provides an overview of factors affecting dermal absorption. Factors influencing absorption are among others related to the skin (e.g. anatomical site, difference between species, metabolism, etc.) and the exposure conditions (e.g. area dose, vehicle, occlusion and exposure duration). In order to provide relevant information for the risk assessment of pesticides, dermal absorption studies should take these aspects into account. With respect to the methods being used nowadays for the assessment of dermal absorption, it is important to realize that neither in vitro nor in vivo animal studies have been formally validated. Available data from various in vitro studies, however, indicate that the use of the total absorbed dose (i.e. the amount of test substance in the receptor medium plus amount in the skin) could be used in a quantitative manner in risk assessment. Tape stripping of the skin can be adequate to give a good indication of test chemical distribution, and hence its immediate bioavailability. 

Biofilm development is affected by both physical and chemical factors. The abundance and condition of bacteria in the water column plays a major role in initial rate of settlement on a surface 181]. Surface factors such as wettability [82] and critical surface tension [83], surface hydrophobicity [84], fluid dynamic forces [85], shear stress [86], electrolyte concentration [87] and metabolic inhibitors [88] can all affect microbial attachment, adhesion or growth. The low surface energy of a gorgonian octocoral has been implicated as a passive fouling resistance mechanism used in conjunction with other antifouling defences [82]. 

The major benefit of using an in vivo test is that it provides an intact biological system including exposure route-specific absorption, distribution, metabolism, and excretion responses, as well as tissue-specific responses to the parent compound and any metabolite(s) that reach the various tissues. Many of the factors affecting these processes in chemical... 

Perfused Organ Screening Chemical Libraries For SAR Contribution to Whole Body Metabolism Factors Affecting Others... 

Small amounts of DDE have been reported in some studies (Table II). The quantity rarely exceeded 5% of the recovered products. In the more common case the amount of DDE recovered did not exceed the amount in the uninoculated controls. The occurrence of DDE as a product shows no consistent relationship to organisms or conditions studied. DDE can be formed easily by the chemical dehydrochlorination of DDT. Therefore, it is reasonable to conclude that DDE is not a normal product of microbial metabolism. The pH of the media may be a factor affecting the formation of DDE. The information given in most of the studies is not suflBcient to determine if this could be the case. 

The ubiquitous flavonoids may be cited as an example of the manifold factors affecting the bioavailability of phytochemicals thus, the bioavailability of flavonoids differs between food sources, predominantly due to the nature of the attached sugar(s). The chemical structure (glycoside or aglycone) of a phytochemical will affect intestinal absorption and first-pass metabolism and will, therefore, modulate its pharmacokinetics [4,6]. 

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