N-Acetylputrescine

N-Acetylputrescine (NacPut), also known as monoacetylputrescine, is an endogenous metabolite of putrescine and a precursor and metabolic intermediate in the biosynthesis of γ-aminobutyric acid (GABA) from putrescine.

[1][2][3] The metabolic pathway is specifically putrescine into N-acetylputrescine by putrescine acetyltransferase (PAT), N-acetylputrescine into N-acetyl-γ-aminobutyraldehyde (N-acetyl-GABAL or N-acetyl-GABA aldehyde) by monoamine oxidase B (MAO-B), N-acetyl-GABAL into N-acetyl-γ-aminobutyric acid (N-acetyl-GABA) by aldehyde dehydrogenase (ALDH), and N-acetyl-GABA into GABA by an unknown deacetylase enzyme.

[1] In 2021, it was discovered that MAO-B does not mediate dopamine catabolism in the rodent striatum but instead participates in striatal GABA synthesis and that synthesized GABA in turn inhibits dopaminergic neurons in this brain area.

[4][3] It has been found that MAO-B, via the putrescine pathway, importantly mediates GABA synthesis in astrocytes in various brain areas, including in the hippocampus, cerebellum, striatum, cerebral cortex, and substantia nigra pars compacta (SNpc).

[4][3] These findings may warrant a rethinking of the actions of MAO-B inhibitors in the treatment of Parkinson's disease.