Quinonoid dihydrobiopterin

BH4 is essential for the AAHs to carry out their respective catalytic reactions and, at least for PAH, the prereductive activation, which appears to produce dihydrobiopterin quinonoid (g-BH2) directly (20). After the PAH catalytic cycle an oxygen atom is incorporated into the cofactor, providing 4a-OH-BH4 which dissociates from the active site. In order to regenerate the functional tetrahydro form of BH4 pterin carbinolamine dehydratase catalyzes the dehydration of 4-OH-BH4 to g-BH2, which is reduced back to by dihydropteridine reductase (Scheme 2). g-BH2 can also be converted to 7,8-dihydropterin (BH2) which can be regenerated to BH4 by dihydrofolate reductase (DHFR). 

Hyland K, Heales SJ. (1993) Tetrahydrobiopterin and quinonoid dihydrobiopterin concentrations in CSF from patients with dihydropteridine reductase deficiency. J Inherit Metab Dis 16 608-610... 

The two oxidation states of (17) that are relevant in biopterin-dependent redox reactions are the four-electron and two-electron reduced forms, tetrahydrobiopterin (19) and p-quinonoid dihydrobiopterin (20), respectively. The oxidation state between these two, i.e. a radical, may also be relevant though it has not been detected as an intermediate in enzymatic reactions. Structurally, pteridines and flavins are rather similar and hence show similar chemical behavior in many respects. As a redox coenzyme, (19) is not encountered nearly as frequently as nicotinamides or flavins. It is, however, the cofactor of three very... 

Of the three aromatic amino acid hydroxylases, the reaction catalyzed by L-phenylalanine hydroxylase has been subjected to mechanistic scrutiny most often (B-71MI11003, B-74MH1005, B-76MI11006). Of a number of isomeric dihydrobiopterins that are possible, it is the p-quinonoid dihydrobiopterin (20) that is the coenzyme-derived product in the reaction catalyzed by this enzyme (Scheme 7) (B-71MIH003). (20) is reduced back to (19) by an... 

Quinonoid (6.R)-dihydrobiopterin (45) was expected to be a labile compound which readily isomerizes to 7,8-dihydrobiopterin (44). When a so-... 

Despite the instability of the quinonoid 6-monosubstituted-6,7-dihydro-8//-pterins it was possible to prepare the 6-methyl- and 6,7-dimethyl-derivatives <85TL4003>, as well as the quinonoid (6R)-dihydrobiopterin (86TL585), as solid materials, by H202 oxidation in the presence of KI. 

The reductant here is tetrahydrohiopterin, an electron carrier that has not been previously discussed and is derived from the cofactor biopterin. Because biopterin is synthesized in the body, it is not a vitamin. Tetrahydrohiopterin is initially formed by the reduction of dihydrobiopterin by NADPH in a reaction catalyzed by dihydrofolate reductase (Figure 23.28). NADH reduces the quinonoid form of dihydrobiopterin produced in the hydroxylation of phenylalanine back to tetrahydrohiopterin in a reaction catalyzed by dihydropteridine reductase. The sum of the reactions catalyzed by phenylalanine hydroxylase and dihydropteridine reductase is... 

The tetrahydrobiopterin is regenerated by reduction of the quinonoid dihydrobiopterin in the presence of NAD(P)H by dihydropteridine reductase ... 

Quinonoid dihydrobiopterin is an extremely unstable compound that can rapidly rearrange (by tautomerization) to 7,8-dihydrobiopterin (Figure 17-21) and be reduced to the tetrahydro form by dihydrofolate reductase ... 

Dihydrobiopterin can exist as a number of isomers. The quinonoid form shown in Eqs. 18-44 and 18-46 is... 

A small number of infants who have phenylketonuria have normal levels of phenylalanine hydroxylase activity, but on normal diets they continue to accumulate phenylalanine as well as other metabolites, including phenylpyruvate, phenyllactate, and phenylacetate. They also have high levels of quinonoid dihydrobiopterin. 

Reaction 1, the substitution of a hydroxyl group for hydrogen in the para position, involves an enzyme, phenylalanine hydroxylase (EC 1.14.3.1) acting with tetrahydrobiopterin and molecular oxygen to yield tyrosine, quinonoid dihydrobiopterin and water [44]. Catalase and another, unidentified, protein are necessary for full enzymic activity—the reaction mechanism and the structure of phenylalanine hydroxylase are not yet fully understood. A second enzyme, dihydropteridine reductase, catalyses the reduction by NADH of the quinonoid dihydrobiopterin to tetrahydrobiopterin. 

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