Recombinant Human ACMSD protein

ACMSD (Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase) is a key enzyme in the kynurenine pathway, a major route of tryptophan metabolism. It catalyzes the decarboxylation of α-amino-β-carboxymuconate-ε-semialdehyde (ACMS) to aminomuconate-ε-semialdehyde (AMS), a critical step that regulates the balance between NAD+ biosynthesis and the production of neuroactive metabolites. By diverting ACMS away from non-enzymatic conversion to quinolinic acid (a neurotoxic compound and precursor of NAD+), ACMSD modulates cellular levels of quinolinic acid, which is implicated in neurodegenerative disorders, immune responses, and oxidative stress. This regulatory function positions ACMSD as a potential therapeutic target for diseases linked to NAD+ dysregulation or quinolinic acid accumulation, such as Alzheimer’s disease, Parkinson’s disease, and chronic kidney disease.

Recombinant ACMSD protein is typically produced using heterologous expression systems (e.g., E. coli or mammalian cells) to enable detailed biochemical and structural studies. The purified protein retains enzymatic activity, allowing researchers to investigate its kinetic properties, inhibitor interactions, and post-translational modifications. Structural studies using recombinant ACMSD, including X-ray crystallography and cryo-EM, have revealed insights into its catalytic mechanism and substrate binding sites, facilitating the design of small-molecule inhibitors. These inhibitors are being explored for their ability to modulate NAD+ levels or reduce neurotoxic quinolinic acid in preclinical models. Additionally, recombinant ACMSD serves as a tool to study tissue-specific metabolic flux in the kynurenine pathway, particularly in the liver, kidneys, and brain, where its expression and activity significantly influence local and systemic homeostasis.