ASL Human

Argininosuccinate lyase (ASL) is a crucial enzyme in the urea cycle, responsible for catalyzing the reversible breakdown of argininosuccinate into fumarate and L-arginine . This enzyme plays a vital role in the biosynthesis of arginine and the production of urea in ureotelic species . The human recombinant form of this enzyme is produced using recombinant DNA technology, which allows for the expression of the human ASL gene in a host organism, typically bacteria or yeast.

ASL is composed of four identical monomers, each consisting of a single polypeptide chain with a molecular weight between 49 and 52 kDa . The entire tetrameric enzyme has a molecular weight between 196 and 208 kDa . Each monomer contains three highly conserved regions that cluster together in the tetramer to form four active sites, allowing for the catalytic activity at each possible active site .

The enzyme’s cleavage of argininosuccinate to form fumarate and arginine occurs through an E1cb elimination reaction . This reaction is initiated by the deprotonation of the carbon adjacent to the arginine, leading to the formation of the products .

The ASL gene is located on chromosome 7 between the centromere and the long (q) arm at position 11.2 . Mutations in the ASL gene can lead to argininosuccinic aciduria, a rare autosomal recessive disorder characterized by deficiencies in the urea cycle . This condition results in the accumulation of argininosuccinate in the body, leading to various clinical symptoms .

The preparation of human recombinant ASL involves the insertion of the human ASL gene into a suitable expression vector, which is then introduced into a host organism such as Escherichia coli or Saccharomyces cerevisiae . The host organism expresses the ASL protein, which is subsequently purified using techniques such as affinity chromatography . The recombinant enzyme can then be used for various research and therapeutic applications.

ASL catalyzes the reversible breakdown of argininosuccinate into fumarate and L-arginine . This reaction is a key step in the urea cycle, which is the major pathway for the detoxification of ammonia in the body . The enzyme’s activity is essential for the continuation of the urea cycle and the production of arginine, which is a precursor for the synthesis of proteins, nitric oxide, and other important molecules .

Deficiencies in ASL activity due to genetic mutations can lead to argininosuccinic aciduria, which is associated with hyperammonemia, developmental delay, and other neurological symptoms . Early diagnosis and treatment are crucial for managing this condition and preventing severe complications .