Other Neurotransmitter Synthesis

1. 1

   L-Glutamate -> GABA + CO2

   Glutamate decarboxylase (GAD65/GAD67) 4.1.1.15 ST-0349 Irreversible/directional PLP (B6)
   In Glutamate

   Out GABA CO2
   › Notes

   B6 deficiency (e.g. isoniazid without pyridoxine) lowers GABA and causes seizures. Anti-GAD antibodies occur in stiff-person syndrome and type 1 diabetes.

2. 2

   L-Histidine -> histamine + CO2

   Histidine decarboxylase (HDC) 4.1.1.22 ST-0350 Irreversible/directional PLP (B6)
   In Histidine

   Out Histamine CO2
   › Notes

   Stored in mast cells and basophils; degraded by diamine oxidase and histamine N-methyltransferase.

3. 3

   Choline + acetyl-CoA -> acetylcholine + CoA-SH

   Choline acetyltransferase (ChAT) 2.3.1.6 ST-0351 Irreversible/directional Acetyl-CoA
   In Choline Acetyl-CoA

   Out Acetylcholine CoA-SH
   › Notes

   Hydrolysed at the synapse by acetylcholinesterase, the target of organophosphates and of anticholinesterase drugs.

4. 4

   L-Arginine + O2 + NADPH -> nitric oxide + L-citrulline

   Nitric oxide synthase (nNOS/eNOS/iNOS) 1.14.13.39 ST-0352 Irreversible/directional NADPH BH4 FAD FMN heme
   In Arginine O2 NADPH

   Out Nitric oxide L-citrulline
   › Notes

   NO activates soluble guanylate cyclase -> cGMP -> smooth-muscle relaxation; the mechanism exploited by nitrates and by PDE5 inhibitors.

Showing all 4 steps.