Disease relevance of ACMSD

• Kinetic and spectroscopic characterization of ACMSD from Pseudomonas fluorescens reveals a pentacoordinate mononuclear metallocofactor [1].

High impact information on ACMSD

• Ultimately, these results suggest for the first time that ACMSD is a metal-dependent enzyme that catalyzes a novel nonoxidative decarboxylation [1].
• The enzyme alpha-amino-beta-carboxy-muconic-epsilon-semialdehyde decarboxylase (ACMSD) plays an important role in the biodegradation of 2-nitrobenzoic acid in microorganisms and in tryptophan catabolism in humans [1].
• We report that the overexpressed ACMSD enzyme from Pseudomonas fluorescens requires a divalent metal, such as Co(II), Fe(II), Cd(II), or Mn(II), for catalytic activity and that neither a redox reagent nor an organic cofactor is required for the catalytic function [1].
• The activity of ACMSD determines whether the metabolites in both pathways are converted to quinolinic acid for NAD biosynthesis or to acetyl-CoA for the citric acid cycle [2].
• Progress in the biochemical and structural characterization of ACMSD not only sheds light on the active site of this protein family but also promises the elucidation of the detailed catalytic mechanism of these novel transition metal-dependent nonoxidative decarboxylation reactions [3].

Biological context of ACMSD

• The cDNA encodes a unique open reading frame of 336 amino acids and displays little homology to any known enzymes or motifs in mammalian databases, suggesting that ACMSD may contain a new kind of protein fold [4].
• Utilizing partial amino acid sequences obtained from highly purified porcine kidney ACMSD, a cDNA encoding human ACMSD was cloned and characterized [4].

Anatomical context of ACMSD

• Increased serum QUIN concentrations are probably due to the increased substrate availability and the decreased activity of aminocarboxymuconate-semialdehyde decarboxylase in the liver, accompanying the increased monocyte/macrophage infiltration into the liver after hepatic injury [5].

Associations of ACMSD with chemical compounds

• In this report, we address the molecular basis underlying quinolinate metabolism and the regulation of ACMSD expression [4].
• Brain ACMSD messages was down- and up-regulated in response to low protein diet and streptozocin-induced diabetes, respectively [4].
• Thus, ACMSD is a critical enzyme for tryptophan metabolism [6].
• Although DEHP could not be tested because of its low solubility, MEHP reversibly inhibited ACMSD from rat liver and mouse kidney, and also the recombinant human enzyme [6].
• D-Galactosamine treatment significantly decreased activities of hepatic aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) resulting in increased QUIN concentrations in serum and tissues [5].

Analytical, diagnostic and therapeutic context of ACMSD

• The kidney alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group [7].
• PCR amplifications and DNA sequencing revealed DNA fragments encoding a polypeptide homologous to 2-amino-3-carboxymuconate 6-semialdehyde decarboxylase and anthranilate 1,2-dioxygenase [8].

References