The choice of route for practical purposes is generally dictated by: (a) the likely route by which man will be exposed; and (b) whether the chemical will produce local injury at the site of exposure.
2.3.1 General considerations Many chemicals will become distributed in various environmental media or will be used for different purposes, and substantially different populations may be at risk.
Carbamoyl phosphate utilizedin pyrimidine nucleotide synthesis differs from that synthesized in the ureacycle; it is synthesized from glutamine instead of ammonia and is synthesizedin the cytosol.
The methylgroup (recall that thymine is 5-methyl uracil) is donated by 5,10-methyleneTHF, similarly to the donation of methyl groups during the biosynthesis of thepurines.
Relatively low levels ofnucleotides result in decreased inhibition of de novo synthesis, resulting infurther overload of the non-functioning salvage pathway and increased uric acidproduction.
In the presence of 5,10-Methylenetetrahydrofolate and the enzyme thymidylate synthetase, the carbongroup is both transferred to the pyrimidine ring and further reduced to amethyl group.
A less severe immunodeficiency results whenthere is a lack of purine nucleoside phosphorylase (PNP), anotherpurine-degradative enzyme.
Thisaccumulation of uric acid typically occurs when the body has difficultyprocessing certain protein substances called purines (PURE-EENS) that are foundnaturally in our diets.
Production and use Field studies Assessment of working and environmental of chemicals conditions and of health status of workers and general population Epidemiological studies Clinical evaluation of experimental prophylactic, diagnostic and therapeutic methods Adjustment and correction of requirements for health and environmental protection The use of these three types of information for the purposes of tissue and organ dose estimation requires the postulation of models to describe the absorption, distribution, retention, biotransformation, and excretion of the original chemical or its metabolites, as a function of time (see Chapter 4).
However, salvage pathways exist to convert purines back to their parentnucleotides and are therefore energy saving – accomplished by the followingenzymes:
Two inherited disorders affecting pyrimidine biosynthesis are theresult of deficiencies in the bifunctional enzyme catalyzing the last two stepsof UMP synthesis, orotate phosphoribosyl transferase and OMP decarboxylase.
Deficiencies in either adenosinedeaminase or in the purine nucleoside phosphorylase lead to twodifferent immunodeficiency diseases by mechanisms that are not clearly understood.
The stability of the substance under environmental conditions is then evaluated by standard analytical methods and the influence of the chemical on the self-purification processes of natural waters is studied.
In the catobilsm of purine nucleotides, IMP is furtherdegraded by hydrolysis with nucleotidase to inosine and thenphosphorolysis to hypoxanthine.
food additives and pesticides, the regulations will often provide specifications of purity for the compound in actual use and recommended test protocols may specify that toxicity evaluations are to be conducted with samples that meet these specifications (WHO, 1967).