Disease relevance of dihydrobiopterin

• A small amount of 7,8-dihydrobiopterin was found in his serum; this distinguishes the case from that of malignant hyperphenylalaninaemia [1].

High impact information on dihydrobiopterin

• We have determined the X-ray crystal structure (1.7 A) of a truncated functional form of human tryptophan hydroxylase with the bound cofactor analogue 7,8-dihydro-L-biopterin, providing the first atomic-resolution information for the catalytic domain of this important enzyme [2].
• The 2.3 A crystal structure of the catalytic and tetramerization domains of rat tyrosine hydroxylase (TyrOH) in the presence of the cofactor analogue 7,8-dihydrobiopterin and iron shows the mode of pterin binding and the proximity of its hydroxylated 4a carbon to the required iron [3].
• In concentrations up to 0.4 mM q-6,6-Me2PH2 is not an inhibitor of phenylalanine hydroxylase, in contrast to 6-methyl-7,8-dihydropterin and 7,8-dihydrobiopterin which inhibit competitively, with Ki's of 0.2 mM and 0.05 mM, respectively [4].
• Dihydropteridine reductase (DHPR) catalyses the conversion of quinonoid dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4), which serves as the obligatory cofactor for the aromatic amino acid hydroxylases [5].
• Using reversed-phase high-performance liquid chromatography and redox electrochemical detection, measurement of tetrahydrobiopterin in the absence (a) and presence (b) of bisulphite enables the concentration of quinonoid dihydrobiopterin to be calculated by subtraction (a - b) [6].

Biological context of dihydrobiopterin

• The crystal structure of the dimeric catalytic domain (residues 118-424) of human PheOH (hPheOH), cocrystallized with the oxidized form of the cofactor (7,8-dihydro-L-biopterin, BH(2)), has been determined at 2.0 A resolution [7].
• Of particular interest was the reactivity demonstrated by 7,8-dihydrobiopterin because of the potential physiological significance of this reaction both in the regeneration of tetrahydrobiopterin, a cofactor for various biological hydroxylations, and as a step in the biosynthesis of this compound from GTP [8].

Anatomical context of dihydrobiopterin

• However, N-acetyl-serotonin inhibition of sepiapterin reductase, an enzyme whose previously only known function was the reduction of sepiapterin to 7,8-dihydrobiopterin, completely inhibited biosynthesis of tetrahydrobiopterin by bovine adrenal medulla extracts [9].

Associations of dihydrobiopterin with other chemical compounds

• The three forms, isolated in 65% yield by preparative chromatofocusing, are stable in 0.05 M phosphate buffer, pH 6.8, containing 1 mM beta-mercaptoethanol and exhibit similar kinetic constants when the catalytic activities of the isolated forms are compared with quinonoid dihydrobiopterin as substrate [10].
• The various interactions of rat liver dihydrofolate reductase with two unconjugated 7,8-dihydropteridines, 7,8-dihydrobiopterin and 6-methyl-7,8-dihydropteridine, have been compared with those of 7,8-dihydrofolate and folate [8].
• Tetrahydrobiopterin, the natural pteridine cofactor for aromatic amino acid hydroxylases, was produced stereopecifically with reference to the C-6 chiral center from 7,8-dihydrobiopterin by the action of dihydrofolate reductase [11].

Gene context of dihydrobiopterin

• A sensitive high-performance liquid chromatographic-fluorometric assay for dihydrofolate reductase in adult rat brain, using 7,8-dihydrobiopterin as substrate [12].

Analytical, diagnostic and therapeutic context of dihydrobiopterin

• Determination of quinonoid dihydrobiopterin by liquid chromatography and electrochemical detection [13].

References