Biopterin

• 2-amino- 6-( L -erythro- 1,2- dihydroxypropyl) - 3H- pteridin -4-one
• (S- (R *, S *) )-2- amino-6 - (1,2- dihydroxypropyl) - 1 H- pteridin -4-one

Pale yellow crystals

• 250-280 ° C ( decomp., ( 1'R, 2'S )-form )
• > 300 ° C ( ( 1'R, 2'R )-form )

Attention

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Biopterin is a heterocyclic compound as a redox cofactor in the metabolism significant. The main structural feature is a heterocyclic pteridine ring system, so that it is a derivative of the pterin.

Biochemically biopterin is formed by oxidation of tetrahydrobiopterin with GTP.

History

The compound was discovered in the 1950s by four research groups in different sources. In the U.S., a working group of the Lederle Laboratories, a division of American Cyanamid Company, from 4000 liters isolated human urine by adsorption on activated carbon, countercurrent distribution and chromatography about 20 milligrams of a substance which promoted the growth of the protozoan Crithidia fasciculata in a biological test. EL Patterson called biopterin and headed out degradation experiments the structural formula from.

Regardless reported in the same year HS Forrest and HK Mitchell of the California Institute of Technology ( Pasadena ), that they had the substance, among other pteridines from the fruit fly Drosophila melanogaster (wild type ) was isolated. They made the same proposed structure.

On the Chemical Institute of the University of Zurich Max Viscontini and employees had the substance ( there BH2 called ) also discovered in Drosophila melanogaster.

Finally found at the Max Planck Institute in Munich, Adolf Butenandt and Heinz Rembold biopterin in queen cells jelly ( royal jelly ) of the honeybee (Apis mellifera ).

In the aftermath biopterin has not been proven in numerous organisms; its presence is ubiquitous, which (see below) is from its biochemical function understandable.

Properties

Biopterin forming small yellow crystals of spherical habitus, the char to melt on heating to 250 to 280 ° C without. In water, they are moderately soluble, but better. Than both in dilute hydrochloric acid and in dilute sodium hydroxide solution The solutions fluoresce under UV light. The polarimeter to effect a clockwise rotation of the plane of polarized light, thus showing optical activity. Said molecule is chiral; the two carbon atoms of the side chain with the HO- ligands are chiral centers. In this case, 22 = 4 stereoisomers are possible: RR, SS, RS, SR according to the Cahn -Ingold-Prelog - Convention. These can also be defined as two pairs of diastereomers having the erythro or threo configuration, in analogy to the carbohydrates and erythrose Threose.

Syntheses

The small amount of Biopterins natural origin did not allow the explorers at that time to determine the configuration of the isolated compound. To elucidate biopterin therefore had to be synthesized from a block in the chiral pool whose configuration was certain. This was found in the class of carbohydrates ( monosaccharides). Thus synthesized Patterson et al. the pterin of L- rhamnose or L- arabinose, the chemically modified derivative of 5 -deoxy -L- arabinofuranoside, and 2,4,5 -triamino -3 ,4- dihydropyrimidine -4-one (often after its tautomers 2,4,5 called -triamino -4- hydroxypyrimidine, 2,4,5 - triaminopyrimidine, or better -4-ol ). L-arabinose has to the carbon atoms C- 3 and C- 4, the erythro- configuration, which consequently also in the derivative, and finally the side chain of Biopterins (C-1 ', C -2' ) had to be present. The configuration is 1'S, 2'R ( erythro ).

Picture: Reaction of 2,4,5 -triamino -3 ,4- dihydropyrimidine -4-one with 5- deoxy -L- arabinofuranoside. The first reaction step is undoubtedly the formation of an N- glycoside and azomethine ( Schiff base imine ). Because these can be formed with both of the amino group at C- 4 and C- 5, positional isomers result; in the picture, only one is shown. The next steps, which include dehydration, lack of clarity; an Amadori rearrangement was discussed.

However, since this condensation reaction was not selective and gave a poor yield, further syntheses have been developed. From D- xylose and D -threo- diastereoisomer was obtained which did not show growth-promoting effect of Crithidia fasciculata. Viscontini employees and optimized the synthesis of 5- deoxy -L- arabinofuranoside in several works. This is a key intermediate, a new way of L- tartaric acid was found .. Also D -ribose can be used as a starting material later. Further syntheses are quoted at.

Biological Significance

Biopterin - precisely the derived therefrom redox 7,8- dihydrobiopterin / 5,6,7,8- tetrahydrobiopterin ( BH4 latter also abbreviated ) - plays an important role in metabolism as a cofactor. In contrast to the pteridine derivatives of folic acid and riboflavin, it may be synthesized by the human body itself, and thus is not essential. Only the tetrahydro form of the Biopterins is biologically active.

Of particular importance is the Biopteridin redox system to in the oxidation of aromatic rings. Such oxidation is, for example, in the biosynthesis of the amino acid tyrosine by phenylalanine hydroxylase for phenylalanine, in the synthesis of catecholamines in the step of oxidation of tyrosine to L -dopa by tyrosine hydroxylase or the serotonin biosynthesis at the step of oxidation of tryptophan to 5 -hydroxytryptophan by tryptophan hydroxylase instead. A special feature of this oxidation is that they require the presence of molecular oxygen ( see also figure at the bottom ).

Disturbances in biopterin metabolism, because of the importance for the metabolism of aromatic amino acids including on so-called "atypical" Phenylketonurien.

Nitric oxide synthase (NOS ), which is oxidized over a plurality of stages of arginine to nitric oxide (NO ) and citrulline and the alkylglycerol monooxygenase ( AGMO ) that cleaves ether lipids are also tetrahydrobiopterinabhängig.

The redox dihydrobiopterin / tetrahydrobiopterin is relatively complex - you look at this example, the redox cofactors of NAD or FAD. For the regeneration of the oxidized from the reduced form of a separate enzyme system provides: the pterin -4a - carbinolamine dehydratase ( EC 4.2.1.96 ) and dihydropteridine reductase ( EC 1.5.1.34 ). The following figure symbolizes the associated cycle: