Possible Interaction: Tyrosine and Tetrahydrobiopterin

“BH4 is a … intracellular concentrations of BH4, … tyrosine ), TPH (an enzyme-synthesizing serotonin and melatonin from tryptophan), PAH (an enzyme required for complete degradation of phenylalanine to tyrosine, finally … a dopamine deficiency in the nigrostriatal dopamine neurons, and is caused by mutations of one allele of the GCH gene.”

“Various tetrahydro- and dihydro-analogs of tetrahydrobiopterin , including 6,7-dimethyl-tetrahydropterin, 6-methyl-tetrahydropterin, 6-hydroxymethyl-tetrahydropterin, tetrahydropterin, 7,8-dihydrobiopterin, 7,8-dihydroxanthopterin, and sepiapterin, also prevent nitration of tyrosines caused by the reactive nitrogen species.”

“Under normal conditions the intracellular BH4 level is thought to play a pivotal role in not only the regulation of tyrosine and tryptophan hydroxylases, but also in the initial and rate-limiting steps in the biosynthesis of the catecholamines and serotonin.”

“Increasing … of tetrahydrobiopterin to 1,000 µmol/kg resulted in elevation … concentrations, a brief increase in the activity of tyrosine and tryptophan hydroxylase 1 h postadministration, and increased turnover of dopamine and serotonin metabolites lasting …. However, 2 of 12 (17%) mice died following administration of this dose of cofactor.”

“ Tyrosine at 100 μM and oxygen at 94 μM were inhibitory on Fraction I with tetrahydrobiopterin as cofactor.”

“At high concentrations tyrosine inhibited the enzymatic reaction with any one of the four tetrahydrobiopterin cofactors.”

“The enzyme, for example, is markedly inhibited by its substrate, tyrosine , in the presence of tetrahydrobiopterin , but not in the presence of 6,7-dimethyltetrahydropterin.”