Biopterin neopterin

R15. Rokos, H Rokos, K., Frisius, H., and Kirstaedter, H. J., Altered urinary excretion of pteridines in neoplastic diseases. Determination of biopterin, neopterin, xanthopterin, and pterin. Clin. Chim. Acta 105, 275-286 (1980). 

Biopterin, neopterin and xanthopterin have seen an increasing interest in their determination since a relation between their urinary level and certain malign proliferations has been found. ... 

A strategy has been described for the synthesis of 2-ethyIthio-6-(3-hydroxy-1,2-0-isopropylidenepropyl)pteridin-4(3//)-one 90 which can be used as a useful intermediate for the conversion of neopterin to biopterin. Diaminopyrimidinone 86 reacts with D-arabinose phenylhydrazone 87, the obtained diastereomeric mixture 88 is converted into its isopropylidene derivative 89 which under oxidation conditions yields 90 <00H(53)1551>. 

Native urine should be protected from light and stored at -20°C until processed. Oxidized urine sample can be stored at room temperature, but light protection is still recommended. Two procedures for the oxidation of urine (and other samples) are used (1) oxidation with manganese dioxide (Mn02) under acidic conditions, and (2) oxidation with iodine (iodine/potassium iodide, I2/KI) under acidic and basic conditions. The Mn02 oxidation method is a routine method used to quantify total pterins (fully oxidized neopterin, monapterin, biopterin, primapterin, isoxanthopterin, and pterin) the I2/KI method is used according to Fukushima and Nixon [11] for the differential oxidation of pterins and quantification of BH4. Total biopterin represents the sum of BH4, BH2, and fully oxidized biopterin. Under acidic conditions BH4 and BH2 are oxidized to biopterin, while under basic conditions only BH2 is oxidized to... 

Plasma, CSF, and amniotic fluid standard mixture (40 nM neopterin 40 nM biopterin) dilute 1 ml of the urine standard mixture with 59 ml of 0.05 M HC1. Store aliquots at -20°C. 

Fig. 6.1.6 HPLC of the pterins standard mixture using an isocratic system. Bio biopterin, Ixa isoxanthopterin, Mon monapterin, Neo neopterin, Pte pterin...

Table 6.1.5 Reference values for pterins in urine, serum, and cerebrospinal fluid. Bio biopterin, CSF cerebrospinal fluid, Neo neopterin, S serum, Sep sepiapterin, U urine...

Plasma neopterin and biopterin values depend strongly upon the actual hyperphenylalaninemia. 

GTPCH activity measurements are not available in external control programs and can only be compared by exchanging results from other laboratories (for examples see www.bh4.org). Control biopterin and neopterin samples are commercially available from Dr. Schircks Laboratories, Jona, Switzerland (www.schircks.com). We recommend using internal controls (e.g., normal control fibroblasts in each enzyme... 

Chromatograms chromatogram standards involve neopterin, biopterin, mon-apterin, pterin, and isoxanthopterin. 

A confluent fibroblast cell monolayer in 78-cm2 plates, cultured in fresh DMEM (see section 6.1.4.1, subheading Specimen ), is incubated with recombinant human INF-y (2.5 pi per 5 ml DMEM 1250 U) and TNF-a (2.5 pi per 5 ml DMEM 500 U). After stimulation for 24 h, cells are harvested by trypsinization, washed with PBS, and immediately lysed for neopterin and biopterin measurements and for GTPCH activity assay. 

First isolated from human urine, biopterin (Fig. 15-17) is present in liver and other tissues where it functions in a reduced form as a hydroxylation coenzyme (see Chapter 18).338 It is also present in nitric oxide synthase (Chapter 18).341/342 Other functions in oxidative reactions, in regulation of electron transport, and in photosynthesis have been proposed.343 Neopterin, found in honeybee larvae, resembles biopterin but has a D-erythro configuration in the side chain. The red eye pigments of Drosophila, called drosopterins, are complex dimeric pterins containing fused 7-membered rings (Fig. 15-17).344 345... 

A much more expensive route to (11) has been described which involves periodate cleavage of L-neopterin [33]. An analogous but synthetically uninteresting synthesis involves photolysis of either biopterin or neopterin in a phosphate buffer at pH 10 in the absence of oxygen. Subsequent introduction of oxygen results in oxidation of the intermediate 5,8-dihydropterin-6-car-boxaldehyde to give (11) in unspecified yield [34]. 

Both biopterin (30) and neopterin (31) belong to the family of naturally occurring 6-hydroxypropylpterin and are isolated as major pterins from almost all higher animals. Due to the existence of 2 chiral centers on the propyl side chain, 4 diastereomers are possible in biopterin and neopterin, and isomers 32-37 are found and considered to be minor or exceptional pterins. The absolute configurations of biopterin and neopterin are R,2 S and l S,2 R, respectively, and expedient notations of L-erytho, for biopterin, and d-erythro, for neopterin, have frequently been used. Following these notations, the di-... 

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