Pyridoxal 5'-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic L-amino acid decarboxylase and vitamin B(6) deficiency states.

J Neurochem. 2010 Apr 9;

Authors: Allen GF, Neergheen V, Oppenheim M, Fitzgerald JC, Footitt E, Hyland K, Clayton PT, Land JM, Heales SJ

Abstract Pyridoxal 5'-phosphate, the active form of vitamin B(6), is an essential cofactor for multiple enzymes, including aromatic L-amino acid decarboxylase that catalyses the final stage in the production of the neurotransmitters dopamine and serotonin. In two patients with inherited disorders of vitamin B(6) metabolism we observed reductions in plasma aromatic L-amino acid decarboxylase activity. In one patient this change was related to an increase in K(m) for pyridoxal 5'-phosphate. Furthermore pyridoxal 5'-phosphate-deficient human SH-SY5Y neuroblastoma cells were found to exhibit reduced levels of aromatic L-amino acid decarboxylase activity and protein but with no alteration in expression. Further reductions in activity and protein were observed with the addition of the vitamin B(6) antagonist 4-deoxypyridoxine, which also reduced aromatic L-amino acid decarboxylase mRNA levels. Neither pyridoxal 5'-phosphate deficiency nor the addition of 4-deoxypyridoxine affected AADC stability over 8hrs with protein synthesis inhibited. Increasing extracellular availability of pyridoxal 5'-phosphate was not found to have any significant effect on intracellular pyridoxal 5'-phosphate concentrations or on aromatic L-amino acid decarboxylase. These findings suggest that maintaining adequate pyridoxal 5'-phosphate availability may be important for optimal treatment of aromatic L-amino acid decarboxylase deficiency and L-dopa-responsive conditions.

PMID: 20403077 [PubMed - as supplied by publisher]

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