N-Acetylputrescine - Misplaced Pages

(Redirected from N-acetylputrescine) Endogenous GABA precursor

N-Acetylputrescine
Names

IUPAC name N-(4-aminobutyl)acetamide
Other names Acetylputrescine; Monoacetylputrescine; NacPut
Identifiers
CAS Number	5699-41-2
3D model (JSmol)	Interactive image
ChEBI	CHEBI:17768
ChEMBL	ChEMBL81241
ChemSpider	109095
ECHA InfoCard	100.219.140
EC Number	691-457-0
KEGG	C02714
PubChem CID	122356
UNII	8FTM5ZL5A6
CompTox Dashboard (EPA)	DTXSID80205596
InChI InChI=1S/C6H14N2O/c1-6(9)8-5-3-2-4-7/h2-5,7H2,1H3,(H,8,9)Key: KLZGKIDSEJWEDW-UHFFFAOYSA-N
SMILES CC(=O)NCCCCN
Properties
Chemical formula	C₆H₁₄N₂O
Molar mass	130.19 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references

Chemical compound

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.

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. This pathway is a minor alternative pathway to the major and primary pathway in which GABA is synthesized from glutamate. There is also another alternative pathway in which putrescine is converted into GABA with γ-aminobutyraldehyde (GABAL or GABA aldehyde) as an intermediate instead. 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.

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

References

^ 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.
^ Seiler N (June 2004). "Catabolism of polyamines". Amino Acids. 26 (3): 217–233. doi:10.1007/s00726-004-0070-z. PMID 15221502.
^ 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.
^ 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.

Neurotransmitter metabolic intermediates

Catecholamines

Anabolism

Phenylalanine → Tyrosine → DOPA (levodopa) → Dopamine → Norepinephrine → Epinephrine

Catabolism

Dopamine	3,4-Dihydroxyphenylacetaldehyde (DOPAL) 3,4-Dihydroxyphenylacetic acid (DOPAC) Homovanillyl alcohol Hydroxytyrosol (3,4-dihydroxyphenylethanol; DOPET) 3-Methoxytyramine (3-MT) Homovanillic acid (HVA)
Norepinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) 3,4-Dihydroxymandelic acid (DHMA) Normetanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL) Vanillylmandelic acid (VMA) 3,4-Dihydroxyphenylethylene glycol (DOPEG, DHPG) 3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG)
Epinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) Metanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL)

Tryptophan→Serotonin

Anabolism	Tryptophan 5-Hydroxytryptophan (5-HTP)
Catabolism	5-Hydroxyindoleacetaldehyde (5-HIAL) 5-Hydroxyindoleacetic acid (5-HIAA) 5-Hydroxytryptophol (5-HTOL)

Serotonin→Melatonin

Trace amines

GABA

Amino acid metabolism metabolic intermediates

K→acetyl-CoA

lysine→	Saccharopine Allysine α-Aminoadipic acid 2-Oxoadipic acid Glutaryl-CoA Glutaconyl-CoA Crotonyl-CoA β-Hydroxybutyryl-CoA
leucine→	β-Hydroxy β-methylbutyric acid β-Hydroxy β-methylbutyryl-CoA Isovaleryl-CoA α-Ketoisocaproic acid β-Ketoisocaproic acid β-Ketoisocaproyl-CoA β-Leucine β-Methylcrotonyl-CoA β-Methylglutaconyl-CoA β-Hydroxy β-methylglutaryl-CoA
tryptophan→alanine→	N′-Formylkynurenine Kynurenine Anthranilic acid 3-Hydroxykynurenine 3-Hydroxyanthranilic acid 2-Amino-3-carboxymuconic semialdehyde 2-Aminomuconic semialdehyde 2-Aminomuconic acid Glutaryl-CoA

G→pyruvate→
citrate

glycine→
serine→

3-Phosphoglyceric acid

G→glutamate→
α-ketoglutarate

histidine→	Urocanic acid Imidazol-4-one-5-propionic acid Formiminoglutamic acid Glutamate-1-semialdehyde
proline→	1-Pyrroline-5-carboxylic acid
arginine→	Agmatine Ornithine Citrulline Cadaverine Putrescine
other	cysteine+glutamate→glutathione: γ-Glutamylcysteine

G→propionyl-CoA→
succinyl-CoA

valine→	α-Ketoisovaleric acid Isobutyryl-CoA Methacrylyl-CoA 3-Hydroxyisobutyryl-CoA 3-Hydroxyisobutyric acid 2-Methyl-3-oxopropanoic acid
isoleucine→	2,3-Dihydroxy-3-methylpentanoic acid 2-Methylbutyryl-CoA Tiglyl-CoA 2-Methylacetoacetyl-CoA
methionine→	generation of homocysteine: S-Adenosyl methionine S-Adenosyl-L-homocysteine Homocysteine conversion to cysteine: Cystathionine α-Ketobutyric acid + Cysteine
threonine→	α-Ketobutyric acid
propionyl-CoA→	Methylmalonyl-CoA