Biopterin reduction

The biologically active relatives of folic acid and biopterin are the tetrahydro compounds with a reduced pyrazine ring. Reduction to this level occurs rapidly in vivo. The corresponding electrochemical process is well illustrated by reduction of the N-methylated analogue 28 [95], Reduction to the 5,8-dihydro stage is a reversible two-electron and two-proton process. The product rapidly tautomerises to the... 

Among the simple pterins isolated from the eyes of Drosophila3 0 is sepiapterin (Fig. 15-17), in which the pyrazine ring has been reduced in the 7,8 position and a short side chain is present at position 6. Reduction of the carbonyl group of sepiapterin with NaBH4 followed by air oxidation produces biopterin, the most widely distributed of the pterin compounds. 

The biopterin product is recycled by elimination of water, reduction using NADPH as the reagent, and reaction with molecular oxygen. The other product, the phenylalanine oxide, rearranges with a hydride shift followed by the loss of a proton to give tyrosine. 

Dihydrofolate reductase (EC 1.5.1.3) catalyzes the reduction of the 5,6 double bond in the H2-folate to form Hi-folate. The activity also converts H2-biopterin... 

The formation of biopterin involves dephosphorylation and reduction of the side chain of dihydroneopterin triphosphate, followed by inversion of the conformation of the two hydroxyl groups, by way of intermediate oxidation to (symmetrical) oxo-groups, catalyzed by sepiapterin reductase. 

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 biopterin hydroperoxide donates an electrophilic oxygen atom to the benzene ring, rather in the way of m-CPBA, though that reagent would not do the trick. The enzyme is essential. The other product is an oxidized biopterin and is recycled by reduction by NADPH back to the biopterin. 

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