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]
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| Names | |
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| IUPAC name
N-(4-aminobutyl)acetamide
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| Other names
Acetylputrescine; Monoacetylputrescine; NacPut
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| Identifiers | |
3D model (JSmol)
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| ECHA InfoCard | 100.219.140 |
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PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C6H14N2O | |
| Molar mass | 130.19 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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][2][3] This pathway is a minor alternative pathway to the major and primary pathway in which GABA is synthesized from glutamate.[1] There is also another alternative pathway in which putrescine is converted into GABA with γ-aminobutyraldehyde (GABAL or GABA aldehyde) as an intermediate instead.[1] It has been estimated that about 2 to 3% of GABA is synthesized from putrescine in the mouse brain, whereas in the case of the rat brain, the amount was negligible.[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.[4][3]
References
edit- ^ a b c d e Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H (2002). "GABA and GABA Receptors in the Central Nervous System and Other Organs". A Survey of Cell Biology. International Review of Cytology. Vol. 213. pp. 1–47. doi:10.1016/s0074-7696(02)13011-7. ISBN 978-0-12-364617-0. PMID 11837891.
- ^ a b Seiler N (June 2004). "Catabolism of polyamines". Amino Acids. 26 (3): 217–233. doi:10.1007/s00726-004-0070-z. PMID 15221502.
- ^ a b c d e Cho HU, Kim S, Sim J, Yang S, An H, Nam MH, Jang DP, Lee CJ (July 2021). "Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis". Exp Mol Med. 53 (7): 1148–1158. doi:10.1038/s12276-021-00646-3. PMC 8333267. PMID 34244591.
- ^ a b c Nam MH, Sa M, Ju YH, Park MG, Lee CJ (April 2022). "Revisiting the Role of Astrocytic MAOB in Parkinson's Disease". Int J Mol Sci. 23 (8): 4453. doi:10.3390/ijms23084453. PMC 9028367. PMID 35457272.
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