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Monoaminergic Effects of Folinic Acid, l ‐DOPA, and 5‐Hydroxytryptophan in Dihydropteridine Reductase Deficiency
Author(s) -
Goldstein David S.,
Hahn SiHoun,
Holmes Courtney,
Tifft Cynthia,
HarveyWhite Judith,
Milstein Sheldon,
Kaufman Seymour
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64062810.x
Subject(s) - homovanillic acid , folinic acid , monoamine neurotransmitter , carbidopa , monoaminergic , chemistry , endocrinology , dihydroxyphenylalanine , dopamine , medicine , 5 hydroxytryptophan , 3,4 dihydroxyphenylacetic acid , dopaminergic , catecholamine , tyrosine , serotonin , biochemistry , levodopa , chemotherapy , parkinson's disease , fluorouracil , receptor , disease
Plasma and CSF concentrations of endogenous l ‐DOPA, catecholamines, and metabolites of monoamines were assayed in a patient with atypical phenylketonuria due to absent dihydropteridine reductase (DHPR), before and during treatment with folinic acid, Sinemet, and 5‐hydroxytryptophan. The patient had low but detectable levels of l ‐DOPA, 3,4‐dihydroxyphenylacetic acid (DOPAC), and 3,4‐dihydroxyphenylglycol (DHPG) in plasma and low but detectable levels of these compounds and of homovanillic acid (HVA) and 5‐hydroxyindoleacetic acid (5‐HIAA) in CSF, with approximately normal plasma and CSF levels of norepinephrine [noradrenaline (NA)]. Folinic acid treatment approximately doubled plasma levels of l ‐DOPA, NA, DOPAC, and DHPG, compared with values during dietary phenylalanine restriction alone. Detection of l ‐DOPA, catecholamines, and monoamine metabolites in this patient indicates that monoamine synthesis in humans does not absolutely require DHPR. The results are consistent with the existence of an alternative biochemical pathway, with folinic acid treatment augmenting activity along this pathway. Low plasma levels of l ‐DOPA, DOPAC, and DHPG may reflect decreased catecholamine synthesis and turnover in sympathetic nerves, with compensatory increases in exocytotic release normalizing plasma NA levels.