Endogeneous metabolism

Many of the species involved in the endogenous metabolism can undergo a multitude of transformations, have many reaction channels open, and by the same token, can be produced in many reactions. In other words, biochemical pathways represent a multi-dimensional space that has to be explored with novel techniques to appreciate and elucidate the full scope of this dynamic reaction system. 

In Vitro Metabolic Activation. The target cells for in vitro mutagenicity tests often possess a limited (often overlooked) capacity for endogenous metabolism of xenobiotics. However, to simulate the complexity of metabolic events that occur in the whole animal, there is a critical need to supplement this activity. 

D. E. Case, Incorporation into Endogeneous Metabolic Pathways of Small Fragments Derived from I.C.I. 58,834 (Viloxazine) , Xenobiotica 1975, J, 133-143. 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

However, apart from absolute specificity, foreign compounds may also be substrates for enzymes involved in endogenous pathways, often with toxicological consequences. Thus, for example, with VPA (see above), fluoroacetate, and galactosamine (see chap. 7) involvement in endogenous metabolic pathways is a crucial aspect of... 

The liver also has an extensive role in intermediary metabolism and synthesis, and consequently, interference with endogenous metabolic pathways may lead to toxic effects, as discussed in chapter 7 (see sects. 7,8.2 and 7.8.3). 

The primary function of the renal system is the elimination of waste products, derived either from endogenous metabolism or from the metabolism of xenobiotics. The latter function is discussed in detail in Chapter 10. The kidney also plays an important role in regulation of body homeostasis, regulating extracellular fluid volume, and electrolyte balance. 

If an analytic method lacks sufficient specificity, chemical interferences will result in an erroneously high reported concentration. If a measured chemical is introduced as an artifactual contaminant during sample collection or analysis, reported concentrations will also be overestimated. For example, credibly estimating human exposure to phthalates was hindered by the difficulties involved in avoiding specimen contamination with these ubiquitous chemicals the problem was resolved by focus on the much less prevalent metabolic product, the phthalate half-ester (Silva et al. 2004). Alternatively, a chemical measured as a marker of exogenous exposure may be identical with a chemical formed by an unrelated endogenous metabolic pathway. In each of those cases, a rigorous laboratory-method validation should detect the problem before data are reported. More subtly, the measured biomarker of exposure may be chemically identical with a dietary... 

Chapman, S. J. and Gray, T. R. G. (1981). Endogenous metabolism and macromolec-ular composition of Arthrobacterglobisformis. Soil Biol. Biochem. 13, 11-18. 

The relative vulnerability of the secreted zinc to phytate complexatlon has only recently been demonstrated. The injection p zinc deficient rats intraperitoneally with a tracer dose of zlnc allows a portion of this zinc to be in equilibrium with the endogenous metabolic pool. This zinc then is secreted thru the saliva, pancreatic fluid, and bile. Those animals maintained on the phytate containing soy protein contained 2-4 times the radioactivity of the animals fed a casein protein diet (Table II). Therefore, not only does phytate affect the bioavailability of dietary zinc but also the reabsorption of endogenous zinc and thus has a net effect on zinc homeostasis. Since this total phytate effect cannot be measured ly labeling only the dietary pool, the expression of the net effect as the phytateizinc molar ratio is the most sensitive and accurate method of estimating the relative risk of zinc deficiency in any individual or population. 

The fact that some xenobiotic-metabolizing cytochrome P450 isoforms are expressed polymorphically (vide infra) and that individuals may lack totally a certain isoform without any detriment to health indicates that the role of these cytochromes P450 in endogenous metabolism is far from life threatening. 

GC-MS is increasingly employed in studies of inborn errors of metabolism. The potential importance of the developing GC-MS methods in this subject, not only for studying the disorders themselves but in applying them to the investigation of normal endogenous metabolism and finally to the diagnosis of diseased conditions, has warranted the inclusion of a separate section on this topic. 

B17. Boyland, E., and Watson, G., 3-Hydroxyanthranilic acid, a carcinogen produced by endogenous metabolism. Nature 177, 837-838 (1956). 

Endogenous hepatosis comprises endogenous metabolic disorders of the liver cell as a rule, the terminology used in this context refers to the accumulated substances (e. g. glycogenosis), the harmful substrate (e.g. fructose-1 phosphate) or the enzyme defect (e.g. apantitrypsin deficiency). 

FIGURE 36.3 Schematic interrelationship between factors that determine process performance in MBRs. Wastewater characteristics are implicit in this outline. The term biological reactions includes exogenous and endogenous metabolism, extracellular enzymatic activity, and product formation (EPS). 

In protecting the body against toxic metals, MTs interact with endogenous metabolic enzymes such as glutathione and mercapturic acid. This makes sense since cysteine is a substrate of glutathione. Supplements such as cysteine may elevate levels of MTs and zinc in the kidneys. 

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