Pteridines biosynthesis

Xanthopterin and isoxanthopterin in which the carbon atom at position 4 of the pteridine was labeled with were prepared by Korte and Barke-meyer 18) and in a brief communication they stated that S. faecalis R and certain yeasts had some capacity to convert these pteridines to folic acid or to degrade them to uracil 19). If the degradative pathway of pteridines to uracil were reversible this would represent a possible route of pteridine biosynthesis from a pyrimidine arising either via orotic acid or possibly from purines. 

Subsequent knowledge of the stmcture, function, and biosynthesis of the foHc acid coenzyme gradually allowed a picture to be formed regarding the step in this pathway that is inhibited by sulfonamides. The biosynthetic scheme for foHc acid is shown in Figure 1. Sulfonamides compete in the step where condensation of PABA with pteridine pyrophosphate takes place to form dihydropteroate (32). The amino acids, purines, and pyrimidines that are able to replace or spare PABA are those with a formation that requkes one-carbon transfer catalyzed by foHc acid coenzymes (5). 

Pteridine radical cations, trihydrostructure, 3, 282 Pteridine radicals structure, 3, 282 Pteridine radicals, hydrostructure, 3, 282 Pteridine reds structure, 3, 283 Pteridines, 3, 263-327 biosynthesis, 3, 315, 320-322 catabolism, 3, 321... 

Neopterin cyclic phosphate (92) has been isolated as an intermediate in the biosynthesis of pteridines from GTP in Comamonas Tracer studies show that the phosphoryl group in (92) originates from the... 

For the synthesis of drosopterin, tetrahydrobiopterin, sepiapterin, 7-oxopterin and isoxanthopterin, DHN-TP is first converted to the common intermediate 6-pyruvoyl-tetrahydropterin. The biosynthesis of pteridines was studied in zebrafish in relation with the differentiation of neural crest derivatives. The key intermediate in the synthesis of 7-oxobiopterin is the sepiapterin. Pteridins are produced in xanthophores and erythrophores of fish and amphibian species. 

Folate, the anion of folic acid, is made up of three different components—a pteridine derivative, 4-aminobenzoate, and one or more glutamate residues. After reduction to tetrahydrofolate (THF), folate serves as a coenzyme in the Q metabolism (see p. 418). Folate deficiency is relatively common, and leads to disturbances in nucleotide biosynthesis and thus cell proliferation. As the precursors for blood cells divide particularly rapidly, disturbances of the blood picture can occur, with increased amounts of abnormal precursors for megalocytes megaloblastic anemia). Later, general damage ensues as phospholipid... 

There are a number of studies on the biosynthesis of various pteridines, i.e., xanthopterin (65), isoxanthopterin (67), erythropterin (73), leucopterin (68), and pterin (62) (509-511). The most important intermediate of the proposed biosynthetic pathway from guanosine triphosphate (GTP) (604) seems to be di-hydroneopterin triphosphate (H2-NTP) (605), however, because evidence has recently been accumulated indicating that pteridines such as biopterin (70), sepiapterin (81), and drosopterins (87) are synthesized from GTP (604) by way of H2-NTP (605) (Scheme 76) (5/2). 

The mode of action of the sulfonamides as antagonists of 4-aminobenzoic acid (PAB) is well documented, as is the effect of physicochemical properties of the sulfonamide molecule, e.g. pK, on potency (B-81MI10802). Sulfonamides compete with PAB in the biosynthesis of folic acid (44), a vital precursor for several coenzymes found in all living cells. Mammalian cells cannot synthesize folic acid (44), and rely on its uptake as an essential vitamin. However, bacteria depend on its synthesis from pteridine precursors, hence the selective toxicity of sulfonamides for bacterial cells. Sulfonamides may compete with PAB at an enzyme site during the assembly of folic acid (44) or they may deplete the pteridine supply of the cell by forming covalently-bonded species such as (45) or they may replace PAB as an enzyme substrate to generate coupled products such as (46) which are useless to the cell. 

The fifth chapter, Tetrahydrobiopterin and Related Biologically Important Pterins by Shizuaki Murata, Hiroshi Ichinose and Fumi Urano, describes a modern aspect of pteridine chemistry and biochemistry. Pteridine derivatives play a very important role in the biosynthesis of amino acids, nucleic acids, neurotransmitters and nitrogenmonooxides, and metabolism of purine and aromatic amino acids. Some pteridines are used in chemotherapy and for the diagnosis of various diseases. From these points of view, this article will attract considerable attention from medicinal and pharmaceutical chemists, and also heterocyclic chemists and biochemists. 

RING SYNTHESIS BY TRANSFORMATIONS OF OTHER RINGS 7.18.10.1 Biosynthesis of Pteridines... 

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