NADH STIMULATES ENDOGENOUS DOPAMINE BIOSYNTHESIS BY ENHANCING THE RECYCLING OF TETRAHYDROBIOPTERIN IN RAT PHEOCHROMOCYTOMA CELLS

Treatment of Parkinson patients with L-DOPA (3,4-dihydroxy-L-phenylala nine) leads to endproduct inhibition of tyrosine hydroxylase, the key enzyme in dopamine biosynthesis and the enzyme needing tetrahydrobiopt erin and iron as cofactors. To overcome this problem an alternative tr eatment was investigated which attempted to stimulate endogenous dopam ine biosynthesis. Incubation of rat PC 12 cells with NADH (beta-nicoti namide adeninedinucleotide) leads to increased dopamine production. We investigated the possibility that this increase of dopamine biosynthe sis was due to stimulation of quinonoid dihydropteridine reductase, th e enzyme which recycles the inactive dihydrobiopterin to the active te trahydrobiopterin. The experiments showed that whereas NADH is able to increase dopamine production in PC 12 cells (rat phaeochromocytoma ce lls, clone PC 12) up to three-fold, no influence is exerted by NADH on pteridine metabolism; neither are tetrahydrobiopterin concentrations nor the de novo-biosynthesis of pteridines from guanosine triphosphate altered by NADH. Further no influence of NADH on protein de novo synt hesis of quinonoid dihydropteridine reductase was observed. However, N ADH was able to directly increase the catalytic activity of this enzym e. Our results suggest that the stimulation of dopamine biosynthesis b y NADH is due to more rapid regeneration of quinonoid dihydrobiopterin to tetrahydrobiopterin.