Aminocarboxymuconate-semialdehyde decarboxylase (ACMSD)

Aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) is a zinc-dependent metalloenzyme that catalyzes a key step in the kynurenine pathway of tryptophan metabolism, converting 2-amino-3-carboxymuconate-6-semialdehyde to 2-aminomuconate-6-semialdehyde, with the byproduct CO2. This reaction directs tryptophan catabolism away from producing the neurotoxic metabolite quinolinic acid and toward the synthesis of nicotinamide adenine dinucleotide (NAD+), an essential molecule for cellular metabolism. Variants and dysregulation of ACMSD are implicated in neurodegenerative disorders such as Parkinson’s disease, mitochondrial diseases, and may act as a biomarker in nonverbal autism. The enzyme’s central metabolic role makes it a potential target for the treatment of metabolic, inflammatory, and neurodegenerative diseases.

Other names

2-amino-3-carboxymuconate-6-semialdehyde decarboxylasePicolinic acid carboxylasePicolinic acid decarboxylaseAlpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylaseAlpha-amino-beta-carboxymuconate-epsilon-semialdehyde beta-decarboxylase2-amino-3-(3-oxoprop-2-enyl)but-2-enedioate carboxy-lyase

Inhibitors of ACMSD may increase quinolinic acid formation, which is neurotoxic. Activation or stabilization could promote increased NAD+ formation, potentially neuroprotective and anti-inflammatory.