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• W2039019043 abstract "Several reports indicate that biopterin and folate pathways may interact. We examined folate metabolism in PKU patients where hyperphenylalaninaemia leads to a likely excess of THB. We found an increase in total HPLC determined red cell folate in PKU (p=0.0422): specifically, there was an increase in total formyl-H4folate (p=0.0002) and H4folate (p⩽0.0001), and decrease in total 5-methyl-H4folate in PKU patients. At the level of individual oligo-γ-glutamyl coenzymes, we found that formyl-H4folate polyglutamates were virtually all increased in PKU (p=0.0223, 0.0004, 0.0004, 0.0012, and 0.0008 for di-, tri-, tetra-, penta-, and deca-γ-glutamyl formyl-H4folate coenzymes, respectively). Hcy levels did not differ between clinical groups, indicating that folate dependent—Hcy remethylation is not compromised as a consequence of an altered PKU folate disposition. In nature, pentaglutamyl folates are considered the metabolically favoured coenzymes (optimum Km for dependent enzymes). The presented data support this—we found that red cell pentaglutamates gave the best measure of metabolism; pentaglutamyl formyl-H4folate increased in PKU (p=0.0012) and related methenyls behaved similarly, while, pentaglutamyl 5-methyl-H4folate and pentaglutamyl H4folate decreased (p⩽0.0001 and 0.0265, respectively). Furthermore, pentaglutamates showed the best correlations between one-carbon oxidation states of folate, as well as with Hcy (p=0.0003 r=−0.54, 95% CI; −0.724 to −0.272). That PKU might influence folate metabolism in some way is unsurprising: patients with DHPR deficiency accumulate DHB and develop secondary folate deficiency—responsive only to reduced folates, while CSF levels of THB are significantly correlated to monoamines and red cell folate in depression. Further studies to confirm the present findings and to ascertain precisely what mechanism operates in PKU that impacts upon folate homeostasis so profoundly are required." @default.
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• W2039019043 date "2002-08-01" @default.
• W2039019043 modified "2023-10-14" @default.
• W2039019043 title "The impact of phenylketonuria on folate metabolism" @default.
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• W2039019043 doi "https://doi.org/10.1016/s1096-7192(02)00113-0" @default.
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