N-acetylneuraminate pyruvate lyase, also known as sialic acid aldolase, is an enzyme that plays a crucial role in the metabolism of sialic acids. Sialic acids are a family of nine-carbon sugars that are found on the surfaces of cells and are involved in various biological processes, including cellular communication, migration, adhesion, and infection processes . The enzyme catalyzes the reversible cleavage of N-acetylneuraminic acid (Neu5Ac) into N-acetyl-D-mannosamine (ManNAc) and pyruvate .
N-acetylneuraminate pyruvate lyase belongs to the family of lyases, specifically the oxo-acid-lyases, which cleave carbon-carbon bonds . The enzyme is a homotetramer, meaning it consists of four identical subunits. Each subunit contributes to the overall stability and activity of the enzyme. The enzyme exhibits high stability and activity at alkaline pH levels and moderate temperature ranges .
The primary function of N-acetylneuraminate pyruvate lyase is to regulate the levels of sialic acids within the cell. Sialic acids are cleaved from sialoglycans by sialidases (neuraminidases) and can either be recycled in biosynthesis or degraded by N-acetylneuraminate pyruvate lyase . This degradation process is essential for maintaining the balance of sialic acids in the body, which is crucial for normal cellular functions.
Mutations in the gene encoding N-acetylneuraminate pyruvate lyase can lead to various medical conditions. For instance, deleterious variants in the enzyme have been associated with skeletal myopathy and cardiac edema in humans and zebrafish . These conditions are characterized by increased levels of free sialic acid, reduced muscle force and endurance, impaired mitochondrial function, and aberrant sialylation of proteins . Research has shown that N-acetylneuraminate pyruvate lyase is essential for muscle function and regeneration, serving as a general marker of muscle damage .
Human recombinant N-acetylneuraminate pyruvate lyase is used in various research and clinical applications. It is often employed in studies investigating the metabolism of sialic acids and their role in different biological processes. Additionally, the enzyme’s ability to catalyze the reverse aldol condensation reaction makes it a valuable tool for synthesizing sialic acid and its derivatives .