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Induction of GTP-Cyclohydrolase I by Bacterial Lipopolysaccharide: Implications for Nitric Oxide Formation

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Shock, Sepsis, and Organ Failure — Nitric Oxide

Abstract

Pteridines are a class of compounds containing a pyrazino[2,3-d]pyrimidine heterocylus. Pteridines were first detected as pigments in butterfly wings (Hopkins 1889) and were subsequently shown to be widely distributed in living organisms. Two functionally important pteridines, folic acid and riboflavin, can be synthesized from GTP by bacteria but not by mammals, which depend on proper supply of these vitamins in the diet. Other pteridines, such as molybdopterin, neopterin, and biopterin, are synthesized by mammals from GTP (reviewed by Nichol et al. 1985). The biosynthesis of tetrahydrobiopterin from GTP involves three enzymes, GTP-cyclohydrolase I, 6-pyruvoyl tetrahydropterin synthase, and sepiapterin reductase (Fig. 1). In addition to sepiapterin reductase, other reductases might be involved in the last step in the case of impairment or inhibition of sepiapterin reductase (Milstien and Kaufman 1989; Steinerstauch et al. 1989). In addition to its role in supporting the growth of the protozoon Crithidia fasciculata (Patterson et al. 1955), defined biochemical roles for tetrahydrobiopterin have been found in hydroxylation reactions such as phenylalanine 4-mono-oxygenase (Kaufman 1963), alkyl glycol ether mono-oxygenase (Tietz et al. 1964; Kaufman et al. 1990), tyrosine 3-mono-oxygenase (Shiman et al. 1971), and tryptophan 5-mono-oxygenase (Friedman et al. 1972).

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Werner, E.R., Wachter, H., Werner-Felmayer, G. (1995). Induction of GTP-Cyclohydrolase I by Bacterial Lipopolysaccharide: Implications for Nitric Oxide Formation. In: Schlag, G., Redl, H. (eds) Shock, Sepsis, and Organ Failure — Nitric Oxide. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79343-1_11

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