ACMSD important to biological regulation. The reaction mechanism catalyzed by α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase, ACMSD, is unlike that of all other characterized decarboxylases. ACMSD uses a transition metal-dependent non-oxidative decarboxylation reaction to decarboxylate its substrate (Figure 2), ACMS, to form 2-aminomuconate semialdehyde (AMS). The substrate ACMS is an intermediate in both the tryptophan to quinolinate pathways and the 2-nitrobenzoate degradation pathway. This ACMSD reaction makes AMS from ACMS and prevents its otherwise spontaneous transformation into quinolinic acid, a precursor for NAD biosynthesis (Martynowski et al, 2006).

Figure 2. ACMSD regulated pathways ACMS undergoes spontaneous chemical transformation to quinolinic acid. The enzyme catalyst ACMSD, decarboxylates ACMS to 2-aminomuconate semialdehyde (AMS). (Martynowski et al, 2006).

ACMSD regulates the biosynthesis of NAD. Its involvement in regulating NAD synthesis makes this enzyme of interest as a possible target for therapeutic treatment of several diseases. Quinolinic acid, could excite neurons in the central nervous system (CNS) by acting as an agonist at the N-methyl-D-aspartate (NMDA)-sensitive population of glutamate receptors. This observation raised the possibility that the pathway could be involved in various CNS phenomena, including synaptic plasticity and neurodegeneration (Stone & Darlington, 2002). The amount of quinolinic acid in the brain is normally insufficient to cause neuronal damage, only small increases are necessary to cause injury. Micromolar concentrations of quinolinic acid are toxic to cells exposed for several hours (Stone, et al, 2003). Raised cellular quinolinic acid levels are associated with a wide range of neurodegenerative disorders, such as epilepsy, Alzheimer’s disease, and Huntington’s disease. Since ACMS can be diverted by ACMSD to AMS, a benign metabolite, activation of ACMSD could direct metabolic flux of ACMS to complete oxidation in the citric acid cycle and perhaps prevent the progression of these diseases (Martynowski et al, 2006).

ACMSD could reduce man-made pollution Nitroaromatic compounds such as nitrophenols, nitrotoluenes and nitrobenzoates, are used in the synthesis of pesticides, plasticizers, dyes, pharmaceuticals, and explosives. These compounds are found as contaminants in waste waters, rivers, and groundwater, and in the atmosphere. The bacterial strain KU-7, of Pseudomonas fluorescens, can metabolize 2-nitrobenzoate, a nitroaromatic compound, degrading it to ACMS (Hasegawa et al, 2000). Then ACMSD can shunt carbons to acetyl Co-A, that can enter the TCA cycle instead of forming quinolinic acid which may have adverse health effects. ACMSD catalyzed conversion of 2-nitrobenzoate to ACMS allows for an increased amount of metabolized 2-nitrobenzoate, leading directly to complete metabolic detoxofication of nitrobenozate pollutants (Martynowski et al, 2006).