Chemical sensitivity metabolism

One metabolic specialist I saw looked at my medical records and said, You re not going to find answers. We d spent thousands of dollars and I was still sick. She asked me what I d done that had helped, and I told her I ate organic foods and avoided chemical exposures. She told me to keep doing that, which was amazing to me. I don t usually mention my chemical sensitivities to mainstream doctors. 

Mutation. For industrial applications, mutations are induced by x-rays, uv irradiation or chemicals (nitrosoguanidine, EMS, MMS, etc). Mutant selections based on amino acid or nucleotide base analogue resistance or treatment with Nystatin or 2-deoxyglucose to select auxotrophs or temperature-sensitive mutations are easily carried out. Examples of useful mutants are strains of Candida membranefaciens, which produce L-threonine Hansenula anomala, which produces tryptophan or strains of Candida lipofytica that produce citric acid. An auxotrophic mutant of S. cerevisiae that requires leucine for growth has been produced for use in wine fermentations (see also Wine). This yeast produces only minimal quantities of isoamji alcohol, a fusel oil fraction derived from leucine by the Ehrlich reaction (10,11). A mutant strain of bakers yeast with cold-sensitive metabolism shows increased stability and has been marketed in Japan for use in doughs stored in the refrigerator (12). 

Many of the assumptions under which she was working have now been refuted. Her mechanism of action for the adverse effects of pesticides was that continuous exposure slowly damaged our cell s metabolic machinery. This is fundamentally wrong and has no serious scientific proponents today. Curiously, similar arguments and even Silent Spring itself are invoked today by people suffering from Multiple Chemical Sensitivity (MCS) syndrome (this topic to be dealt with in more detail later in this book). 

These chemical effects become important in medicine because living systems operate mostly through the reactions of enzymes, which catalyze all sorts of metabolic reactions but are very sensitive to small changes in their environment. Such sensitivity can lead to preferential absorption of some deleterious isotopes in place of the more normal, beneficial ones. One example in metabolic systems can be found in the incorporation of a radioactive strontium isotope in place of calcium. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

Examples of Synthesis Routes Inherently Safer Than Others As summarized by Bodor (1995), the ethyl ester of DDT is highly effective as a pesticide and is not as toxic. The ester is hydrolytically sensitive and metabolizes to nontoxic products. The deliberate introduction of a structure into the molecule which facilitates hydrolytic deactivation of the molecule to a safer form can be a key to creating a chemical product with the desired pesticide effects but without the undesired environmental effects. This technique is being used extensively in the pharmaceutical industry. It is applicable to other chemical industries as well. 

For convenience, the processes identified in Figure 2.1 can be separated into two distinct categories toxicokinetics and toxicodynamics. Toxicokinetics covers uptake, distribution, metabolism, and excretion processes that determine how much of the toxic form of the chemical (parent compound or active metabolite) will reach the site of action. Toxicodynamics is concerned with the interaction with the sites of action, leading to the expression of toxic effects. The interplay of the processes of toxicokinetics and toxicodynamics determines toxicity. The more the toxic form of the chemical that reaches the site of action, and the greater the sensitivity of the site of action to the chemical, the more toxic it will be. In the following text, toxicokinetics and toxicodynamics will be dealt with separately. 

Animal studies indicate that trichloroethylene can sensitize the heart to epinephrine-induced arrhythmias. Other chemicals can affect these epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Phenobarbital treatment, which increases the metabolism of trichloroethylene, has been shown to reduce the trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1979), whereas high concentrations of ethanol, which inhibits trichloroethylene metabolism, have been found to potentiate trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1981). These results indicate that trichloroethylene itself and not a metabolite is responsible for the epinephrine-induced arrhythmias. In addition, caffeine has also been found to increase the incidence of epinephrine-induced arrhythmias in rabbits exposed to trichloroethylene (White and Carlson 1982). 

Carotenoids are a class of lipophilic compounds with a polyisoprenoid structure. Most carotenoids contain a series of conjugated double bonds, which are sensitive to oxidative modification and cis-trans isomerization. There are six major carotenoids (ji-carotenc, a-carotene, lycopene, P-cryptoxanthin, lutein, and zeaxanthin) that can be routinely found in human plasma and tissues. Among them, p-carotene has been the most extensively studied. More recently, lycopene has attracted considerable attention due to its association with a decreased risk of certain chronic diseases, including cancers. Considerable efforts have been expended in order to identify its biological and physiochemical properties. Relative to P-carotene, lycopene has the same molecular mass and chemical formula, yet lycopene is an open-polyene chain lacking the P-ionone ring structure. While the metabolism of P-carotene has been extensively studied, the metabolism of lycopene remains poorly understood. 

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