A 28-year-old woman exclusively breastfeeding her infant presents with the infant having seizures at 4 months of age. Serum pyridoxine-5'-phosphate levels are elevated in the infant. The mother takes isoniazid for latent TB. Isoniazid forms a hydrazone with pyridoxal-5'-phosphate (PLP), inactivating it. PLP is required as cofactor for aromatic L-amino acid decarboxylase. Deficiency of this enzyme would MOST directly reduce synthesis of which two neurotransmitters?

• A Serotonin and dopamine ✓
• B GABA and glutamate
• C Norepinephrine and acetylcholine
• D Serotonin and GABA

Explanation

Aromatic L-amino acid decarboxylase (AADC, also called DOPA decarboxylase) requires PLP and catalyzes two critical reactions in neurotransmitter synthesis: (1) decarboxylation of L-DOPA to dopamine and (2) decarboxylation of 5-hydroxytryptophan (5-HTP) to serotonin (5-HT). In isoniazid-induced B6 deficiency, AADC activity is reduced, decreasing both dopamine and serotonin synthesis. This manifests as seizures (related to dopamine/serotonin imbalance and secondary GABA reduction from glutamate decarboxylase inhibition). GABA synthesis by glutamate decarboxylase also requires PLP but this is not AADC. The treatment is pyridoxine supplementation given alongside isoniazid prophylaxis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.