7‐Tetrahydrobiopterin is an uncoupled cofactor for rat hepatic phenylalanine hydroxylase

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Abstract
Rat hepatic phenylalanine hydroxylase requires both a tetrahydropterin cofactor and molecular oxygen to convert phenylalanine to tyrosine. During the physiological hydroxylation, a single mol of the natural cofactor, tetrahydrobiopterin, is oxidized for each mol of phenylalanine converted to tyrosine. Artificial conditions have been devised in which the oxidation of the tetrahydropterin is uncoupled from the hydroxylation of the aromatic amino acid substrate. Recently, an isomer of tetrahydrobiopterin, 7-tetrahydrobiopterin, has been isolated from the urine of certain mildly hyperphenylalaninemic children. We report in this communication that 7-tetrahydrobiopterin may be an inefficient cofactor for phenylalanine hydroxylase because, in vitro, the phenylalanine-dependent oxidation of 7-tetrahydrobiopterin is accompanied by the hydroxylation of the aromatic amino acid substrate only about 15% of the time, i.e. the enzymatic oxidation of 7-tetrahydrobiopterin is about 85% uncoupled from the hydroxylation of the amino acid substrate.

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