5-methyltetrahydrofolate and Phenylketonurias

To determine whether levodopa reduces the levels of S-adenosylmethionine in the human central nervous system, cerebrospinal fluid (CSF) concentrations of S-adenosylmethionine, methionine, 3-methoxytyrosine, levodopa and 5-methyltetrahydrofolate were measured in six children with dopamine deficiency before and after treatment. In four, the lack of dopamine was secondary to a reduction in concentration of levodopa and these were treated with levodopa together with a peripheral dopa-decarboxylase inhibitor. In the other two, levodopa in the central nervous system naturally accumulated due to a congenital deficiency of aromatic-L-amino acid decarboxylase and these were treated with pyridoxine (which in this condition lowers central levodopa concentrations). Raising levodopa concentrations in the central nervous system caused a fall in CSF S-adenosyl-methionine concentration and a rise in CSF 3-methoxytyrosine concentration. No change was observed in CSF methionine concentration and in all patients CSF 5-methyltetrahydrofolate concentration was normal. With one exclusion there was a linear relationship between CSF S-adenosylmethionine and 3-methoxytyrosine concentrations. This is the first demonstration of such effects in humans and the implications upon levodopa therapy are discussed.

Topics: Adolescent; Akinetic Mutism; Biopterins; Child, Preschool; Humans; Infant; Levodopa; Methionine; NADH, NADPH Oxidoreductases; Phenylketonurias; Pyridoxine; S-Adenosylmethionine; Tetrahydrofolates; Tyrosine

Topics: Animals; Ascorbic Acid; Biopterins; Child, Preschool; Humans; Hydroxocobalamin; In Vitro Techniques; Infant; Leucovorin; Male; NADH, NADPH Oxidoreductases; Phenylketonurias; Rats; Tetrahydrofolates