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Effects of reduced folates on the acetylation and tetrahydrobiopterin reduction in phenylalanine hydroxylase.
The effects of reduced folates (penta-, di-, and trifolates) on the acetylation and tetrahydrobiopterin (BH4) reduction in phenylalanine hydroxylase (PAH) were examined. Sodium, potassium, lithium, and cesium folates stimulated the acetylation of PAH at 10 and 100 microM. The apparent IC50 values for lithium and cesium folates were in the ranges of 0.07-2.85 and 0.85-3.43 microM, respectively. Sodium and potassium folates showed slightly higher stimulatory effects than the other reduced folates. The BH4 reduction also increased with the folate concentrations, but the apparent IC50 values for sodium, potassium, and lithium folates were 70-180, 2.8-3.3, and 0.85-0.89 microM, respectively. The order of the BH4 reductase activities was sodium folate > potassium folate > lithium folate > cesium folate. Among these reduced folates, lithium folate showed the strongest stimulation of the BH4 reduction. BH4 reductase and PAH activities in fetal rat liver microsomes were increased by the addition of 0.1 microM of sodium folate, but both enzymes were decreased in the presence of 1 mM of reduced folates. These results indicated that the reduction of tetrahydrobiopterin in the liver appears to be the regulated by reduced folates. The different folate types show different effects