Disease relevance of dihydrobiopterin

• At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephropathy, but higher levels of dihydrobiopterin and 3-nitrotyrosine (3-NT)-modified proteins compared with age-matched ZL rats [1].
• A deficiency of dihydrobiopterin synthesis was found in a 27-year-old man with mild mental retardation, rigid spasticity, hyperreflexia, dystonia, myoclonus, and delay in the initiation of action, since age 10 [2].

High impact information on dihydrobiopterin

• Dihydropteridine reductase converts dihydrobiopterin to tetrahydrobiopterin, the required cofactor for the hydroxylation of aromatic amino acids during the synthesis of dopamine and serotonin [3].
• In dihydrobiopterin-containing iNOSoxy, ferrous-dioxy decay was much slower and was not associated with Arg hydroxylation [4].
• NOS-associated H(4)Bip appeared to react with a NOS catalysis product to a derivative distinct from dihydrobiopterin or biopterin [5].
• This inhibition could be reversed by loading the cells with dihydrobiopterin, a precursor of BH4 via the dihydrofolate reductase salvage pathway [6].
• Dissociation constants for dihydrofolic acid and dihydrobiopterin and implications for mechanistic models for dihydrofolate reductase [7].

Chemical compound and disease context of dihydrobiopterin

• Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis [8].

Biological context of dihydrobiopterin

• As a consequence of the low dihydrofolate reductase activity in the brain, dihydrobiopterin intermediate accumulates and inhibits tyrosine and tryptophan hydroxylases and uncouples nitric oxide synthase (nNOS), leading to neurotransmitter deficiency and possibly also to neuronal cell death [9].

Anatomical context of dihydrobiopterin

• Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes [10].
• Tetrahydrobiopterin in cerebrospinal fluid is unstable at room temperature, 100% being lost within 3.5 h, this breakdown does not generate equivalent quantities of dihydrobiopterin and biopterin [11].
• 5. The equilibrium constant of 2.2.10(9) of the enzyme showed that the equilibrium lies much in favor of dihydrobiopterin formation from sepiapterin in rat erythrocytes [12].
• R- and S-tetrahydrobiopterin (but not sepiapterin or dihydrobiopterin) potentiated the endothelium-dependent contractions to acetylcholine but only in aortas from hypertensive rats and in the presence of N(G)-nitro-L-arginine [13].

Associations of dihydrobiopterin with other chemical compounds

• Chronic (3 months) lead exposure increased the quinonoid dihydropteridine reductase activity and the tetrahydrobiopterin content but did not affect the GTP-cyclohydrolase activity and the dihydrobiopterin content [14].
• We have identified an enzyme, TcPTR2 of Trypanosoma cruzi, which though very similar to PTR1 in its primary sequence, can reduce only dihydrobiopterin and dihydrofolate and not oxidized pteridines [15].
• Other redox activities, i.e. the reduction of nitroblue tetrazolium to diformazan (NADPH-diaphorase) or of quinoid-dihydrobiopterin to tetrahydrobiopterin, by NOS appear to be Ca2+/calmodulin-independent [16].
• Sepiapterin was converted only to dihydrobiopterin in the same fractions since dihydrofolate reductase was removed [17].
• L-Tyrosine caused a 2.1-fold increase in dihydrobiopterin, the largest increase found in this study; L-tryptophan also caused dihydrobiopterin to increase but L-phenylalanine did not [18].

Gene context of dihydrobiopterin

• Moreover, in the presence of CE, eNOS catalyzed the oxidation of BH(4) to dihydrobiopterin and biopterin by a process attenuated by high concentrations of superoxide dismutase but not catalase [19].
• Since brain dihydrobiopterin reductase has the same properties as dihydrofolate reductase, this fluorometric procedure can serve as a sensitive assay for dihydrofolate reductase [20].
• Sepiapterin, which is converted to dihydrobiopterin by the enzyme sepiapterin reductase, was as effective a precursor as dihydrobiopterin and has been used in these studies because of its greater stability relative to dihydrobiopterin [21].

Analytical, diagnostic and therapeutic context of dihydrobiopterin

• Prenatal diagnosis of "dihydrobiopterin synthetase" deficiency, a variant form of phenylketonuria [22].
• The diagnosis of defect dihydrobiopterin biosynthesis was made by high performance liquid chromatography of the urine [23].

References