Disease relevance of Aspartylglucosylamine

• Aspartylglycosaminuria (AGU), a severe lysosomal storage disease, is caused by the deficiency of the lysosomal enzyme, glycosylasparaginase (GA), and accumulation of aspartylglucosamine (GlcNAc-Asn) in tissues [1].

High impact information on Aspartylglucosylamine

• The resulting enzyme deficiency allows aspartylglucosamine (GlcNAc-Asn) and other glycoasparagines to accumulate in tissues and body fluids, from early fetal life onward [2].
• These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine [3].
• Supplementation of culture medium with either isoform cleared AGU lymphoblasts of stored aspartylglucosamine when glycosylasparaginase activity in the cells reached 3-4% of that in normal lymphoblasts [4].
• 5. The enzyme activity is competitively protected against this inactivation by its natural substrate, aspartylglucosamine, indicating that this inhibitor binds to the active site or very close to it [5].
• L-Asparagine competitively inhibits the hydrolysis of aspartylglucosamine indicating that both the amino acid and glycoasparagine are interacting with the same active site of the enzyme [6].

Anatomical context of Aspartylglucosylamine

• The sensitivity of the assay also allows direct quantitation of aspartylglucosamine in normal urine and leukocytes of aspartylglycosaminuria patients, and may thus be used in metabolic studies of the compound [7].
• 2. By use of a highly specific and sensitive gaschromatographic-mass-spectrometric technique, 4-N-2-acetamido-2-deoxy-beta-D-glycopyranosyl-L-asparagine (N-acetylglucosaminylasparagine) was found to accumulate in the patient's lymphocytes, but not in those of the control subject [8].
• Biochemical studies showed elevated levels of urinary aspartylglucosamine and very low activity of aspartylglucosaminidase(AGA) in cultured fibroblasts [9].
• The condition is apparently due to decreased activity of aspartylglycosamine amido hydrolase, with accumulation of products of flycoprotein carabolism in cytoplasmic vacuoles in both epithelial and mesenchymal cells [10].
• As a conclusion, the determination of aspartylglucosamine in urine allowed postnatal detection of aspartylglycosaminuria, but in amniotic fluid it was useless in prenatal detection of the disease [11].

Analytical, diagnostic and therapeutic context of Aspartylglucosylamine

• Randomized urine samples from 151 of the 178 retarded children and from 101 healthy children were analyzed quantitatively for aspartylglucosamine by high-performance liquid chromatography [12].
• Three days on a low-protein diet did not change the aspartylglycosamine excretion in the patient showing the highest excretion rate [13].

References