Introduction:

Human Aspartylglucosaminidase (AGA) is an amidohydrolase enzyme which cleaves the amide bond between asparagine and the oligosaccharide chain. It takes part in glycoprotein degradation by utilizing the N-terminal residue of the B subunit(thr 206) and its a amino group. Asp 205 acts as the base. Both a free alpha carboxy and alpha amino group are required on the substrate for catalyis through what is thought to be an autocatalytic mechanism of activation of aspartylglucosaminidase.The secondary and tertiary stucture of the enzyme result from modifications which take place in the lumen of the endoplasmic reticulum.(1) The N-terminal thr206 of the B chain is located at the active site and is essential for the enzymes catalytic ability.(2) Thr206 is exposed by the cleaavage of a single polypeptide (in the endoplasimic reticulum) into 27kDa pro alpha subunits and 17kDa beta subunits. AGA is then transported into the lysosomes via the mannose 6-phospate receptor pathway. "This pathway is based on the recognition of the mannose 6-phosphate marker in the oligosaccharide chains of soluble lysosomal hydrolases by a specific receptor in Golgi and consequent transport of the complex into a prelysosomal compartment." (1)The pro alpha subunits are then trimmed in the lysosomes (by removal of a 10 amino acid peptide from the c-terminal end) and a 24kDa subunit results. (3) The subunits are glycosylated and associated by noncovalent interactions to result in an active enzyme.(4) The active enzyme has a quaternary structure of a heterotetradimer and catalyzes the hydrolyis of the N-glycosidic linkage between asparagine and N-acetylglucosamine resulting in two products.(5) One of the products, the carbohydrate chain, is degraded by the acidic environment of lysosomes. The other product of the reaction catalyzed by AGA is an aspartic acid.(2) A deficiency of AGA acitivty results in aspartylglucosaminuria (AGU), a lysosomal accumulation disease caused by mutations in the gene which codes for AGA.(6)