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 B₆ deficiency states

J. Neurochem. (2010) 114, 87-96. Pyridoxal 5′-phosphate, the active form of vitamin B₆, 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 B₆ metabolism, we observed reductions in plasma aromatic l-amino acid decarboxylase activity. In one patient, this change was related to an increase in Km 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 B₆ 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 aromatic l-amino acid decarboxylase stability over 8 h 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.