Detoxification-excretion

HUMAN HEALTH RISKS Acute Risks headache tiredness nausea diarrhea convulsions tremors respiratory failure irritation of skin, eyes muscle pains Chronic Risks adverse testicular effects liver damage kidney damage affects synthesis of proteins, lipids, detoxification, excretion CNS damage blood disorders. 

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

A susceptible population will exhibit a different or enhanced response to methyl parathion than will most persons exposed to the same level of methyl parathion in the environment. Reasons may include genetic makeup, age, health and nutritional status, and exposure to other toxic substances (e g., cigarette smoke). These parameters result in reduced detoxification or excretion of methyl parathion, or compromised fimction of organs affected by methyl parathion. Populations who are at greater risk due to their imusually high exposure to methyl parathion are discussed in Section 6.7 Populations With Potentially High Exposures. 

Pool concentration of a substance that exceeds the threshold - for example megadose vitamin C - or substances that are excreted unchanged because they cannot be metabolised, such as sugar alcohols, or compounds that are not biologically essential, such as carcinogens, bacterial toxins and some minor plant constituents, are also bioavailable (and thus bioactive) in that they have a metabolic impact, even if this is only the stimulation of detoxification processes, or the use of energy for their excretion. 

Conjugation of polar groups such as amines, carboxylic acids, and phenolic hydroxyl gronps produce water-soluble compounds that are excreted and these reactions therefore fnnction as a detoxification mechanism. 

Initially formed polar metabolites such as phenols and amines may be conjugated to water-soluble terminal metabolites that are excreted into the medium and function as an effective mechanism of detoxification. For example, pentachlorophenol and pentachlorothiophenol produced from pentachloronitrobenzene conjugated represented the major metabolites. Although the naphthalene dihydrodiol was the major metabolite produced from naphthalene, the further transformation... 

The conversion in the animal body of at least some of the water-insoluble chlordan to a water-soluble degradation product must facilitate the elimination of the poison through its excretion into the urine by the kidneys. Moreover, the degradation of chlordan as shown in the present experiments may be a mechanism for its detoxification, as in the case of DDT (1). Only the isolation of the degradation product, its identification, and a study of its toxicity can determine this point. 

The major metabolic pathway of hydrogen sulfide is the oxidation of the sulfide to sulfate in the liver (Beauchamp et al. 1984). Methylation also serves as a detoxification route. Hydrogen sulfide is excreted primarily as sulfate (either as free sulfate or as thiosulfate) in the urine. 

The urea cycle is essential for the detoxification of ammonia 678 Urea cycle defects cause a variety of clinical syndromes, including a metabolic crisis in the newborn infant 679 Urea cycle defects sometimes result from the congenital absence of a transporter for an enzyme or amino acid involved in the urea cycle 680 Successful management of urea cycle defects involves a low-protein diet to minimize ammonia production as well as medications that enable the excretion of ammonia nitrogen in forms other than urea 680... 

---