What does Aspartoacylase enzyme do?

What does Aspartoacylase enzyme do?

Biological function Aspartoacylase is used to metabolize N-acetyl-L-aspartate by catalyzing its deacylation. Aspartoacylase prevents the buildup of N-acetyl-L-aspartate in the brain. It is believed that controlling N-acetyl-L-aspartate levels is essential for developing and maintaining white matter.

What is Canavan’s disease?

Canavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies.

What is the life expectancy of a person with Canavan disease?

Prognosis is variable. In severe Canavan disease, life expectancy is reduced with average survival until 10 years or occasionally longer. In mild Canavan disease, life expectancy is usually normal and the prognosis is good.

What are the signs and symptoms of Canavan disease?

Symptoms of Canavan disease usually appear in the first 3 to 6 months of life and progress rapidly. Symptoms include lack of motor development, feeding difficulties, abnormal muscle tone (weakness or stiffness), and an abnormally large, poorly controlled head. Paralysis, blindness, or hearing loss may also occur.

What chromosome is the ASPA gene on?

By Southern blot analysis of genomic DNA from human/mouse somatic cell hybrid cell lines, Kaul et al. (1994) localized the ASPA gene to human chromosome 17. They refined the localization to 17pter-p13 by fluorescence in situ hybridization. Stumpf (2019) mapped the ASPA gene to chromosome 17p13.

How do people get Canavan disease?

Canavan disease is caused by disruptions or changes (mutations) to the aspartoacylase (ASPA) gene. This mutation is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

What is 17p deletion?

Deletion 17p (del 17p) is a rare genomic aberration found in patients with chronic lymphocytic leukemia (CLL).

What is aspartoacylase?

Aspartoacylase is a hydrolase enzyme ( EC 3.5.1.15, aminoacylase II, N-acetylaspartate amidohydrolase, acetyl-aspartic deaminase, acylase II, ASPA) that in humans is encoded by the ASPA gene. ASPA is responsible for catalyzing the deacylation of N -acetyl-l-aspartate ( N-acetylaspartate) into aspartate and acetate.

What is the pathophysiology of aspartoacylase deficiency?

Mutations that result in loss of aspartoacylase activity are associated with Canavan disease, a rare autosomal recessive neurodegenerative disorder. Aspartoacylase is a dimer of two identical monomers of 313 amino acids and uses a zinc cofactor in each.

What is the zinc cofactor used for in aspartoacylase?

The zinc cofactor is used to lower the pKa of a ligated water so that an attack on N-acetyl-L-aspartate may occur and to stabilize the resulting tetrahedral intermediate along with Arg-63, and Glu-178. A monomer of aspartoacylase with the N-domain in green, C-domain in yellow, and zinc cofactor in red.

What is the role of Aspa in the action of aspartic acid?

ASPA is responsible for catalyzing the deacylation of N -acetyl-l-aspartate ( N-acetylaspartate) into aspartate and acetate. It is a zinc-dependent hydrolase that promotes the deprotonation of water to use as a nucleophile in a mechanism analogous to many other zinc-dependent hydrolases.