Tissue Distribution of Tetrahydrobiopterin Generating Enzymes

Abstract

Tetrahydrobiopterin (BH₄) is the natural cofactor of Phenylalanine, tyrosine and tryptophan hydroxylases as well as nitric oxide synthase^1-5. BH₄ is synthesized from GTP by successive actions of at least three enzymes^2,6, namely, GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin synthase (PTPS) and sepiapterin reductase (SR)^2,6. BH₄ is regenerated by dihydropteridine reductase (DHPR) from quinonoid dihydrobiopterin². The activities of these BH₄-generating enzymes have been measured in various tissues^7–10, but the expression of their genes has not been fully elucidated. Herein, we examined the transcriptional regulation of BH₄-generating enzymes in various tissues. Northern blot analysis was performed with cDNA probes of these enzymes to determine the mRNA levels of the BH₄-generating enzymes. Our purposes are: to examine the spatial spectra of the mRNA of the BH₄-generating enzymes and compare them with their enzyme activities; 2) to determine whether the mRNA expression of these enzymes differ with the tissue.