Pteridines, metabolites

Purines such as xanthine (91), hypoxanthine (92), guanine (93), and uric acid (95) are found in excreta of many insects (Table VI) 48). Uric acid (95) is known to be the main end product of nitrogen metabolism in almost all insects. Various purines are found in the wasp Vespa) and the sawfly Gilpinia) in common with other insects (Table VI). In addition, various pteridines occur in Vespa and in the honeybee (Table VI). The latter also contains xanthurenic acid (52) or kynurenic acid (53), xanthurenic acid 4,8-digiucoside (56), and a yellow pigment, xanthommatin (58), as tryptophan metabolites (Table V). 

The silkworm, Bombyx mori (Bombycidae), contains in various body parts simple alkylamines, tryptophan metabolites, and pteridines (Tables V, VI, and VIII). One of the pteridines, violapterin (78), is synthesized from isoxanthopterin (67) by isoxanthopterin deaminase, occurring in the larvae and adults, and is stored in situ in the larval and adult integument (80). In addition, sepiapterin deaminase in the integument of the lemon mutant silkworm catalyzes the deamination of sepiapterin (81) to 7,8-dihydro-6-lactyllumazine (79) (81). 

Some pteridines and uric acid (95) are detected in locusts of the genera Locust and Schistocerca (Table VI). Kynurine (54) is found in the genus Dociostaurus and xanthommatin (58) in the genus Locust, as tryptophan metabolites (Table V). 

Levy and McNutt (1962) have studied the utilization of the naturally occurring pteridine, xanthopterin (CVIII) by a bacterium isolated from soil, hoping to relate some of the intermediates produced to metabolites formed in the normal biogenesis of pteridines. They isolated from cultures of this organism, and identified by ultraviolet... 

Folic acid is an indispensable pro-vitamin for Man and other mammals, and lack of it quickly causes macrocytic anaemia and gastrointestinal disorders. Hence it was with some trepidation that chemists began to make metabolite antagonists based on the pteridine nucleus. Nevertheless, they were successful and many very valuable drugs have been obtained in this way. 

Now we come to consider the most remarkable relationship ever encountered between a metabolite and its antagonistic analogue. The position occupied on the enzyme by methotrexate, as described above, is the reverse of that occupied by dihydrofolate, of which the Californian workers supply the following details (Bolin et al., 1982). N-1 is unbound, 2-NH2 is bound only to water, as is 0-4. N-3 is bound by a hydrogen bond to Asp-26, N-5 is unbound, and N-8 has a van der Waals bond to Leu-4. Thus, compared to methotrexate, the normal substrate is very loosely bound, at least as regards the pteridine ring. The/ -aminobenzoic and glutamic portions, however, are identically bound in both metabolite and... 

Claims have been made that PGA and related metabolites (xanthopterin and a pteridine carboxylic acid) act as a color-change hormone in the insect Caraustus. According to Karlson (1956), this work is unconfirmed. The studies of Butenandt on royal jelly, discussed in the next section, may however bring the pterins into the ranks of insect hormones. 

AM Bohhnann, H Nau. Folate metabolite pattern in mice following treatment with the antiepUeptic drug valproic acid (VPA) and 2-en-VPA relationship to neural tube defect induction. In W Pfleiderer, H Rokos, eds. Chemistry and Biology of Pteridines and Folates 1977. Berhn Blackwell Science, 1997, pp 313-315. 

Proguanil (Fig. 3.16) was a relatively early antimalarial drug and it is still useful as a first line of defence against the erythrocytic stage of malaria. It is metabolised in the human body to an active metabolite which mimics the pteridine ring in folic acid and acts as a selective inhibitor of folate reductase in the parasite, thus inhibiting its DNA synthesis. 

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