ADA Human

Adenosine Deaminase (ADA), also known as adenosine aminohydrolase, is a crucial enzyme involved in the purine nucleotide catabolism pathway. It catalyzes the hydrolytic deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively . This enzyme is expressed in virtually all tissues, with particularly high levels in T-lymphocytes .

The human ADA enzyme is a monomeric protein with a molecular weight of approximately 40-42 kDa . The enzyme’s structure consists of 362 amino acids, excluding the initiator methionine . ADA belongs to the α/β class of proteins, characterized by a mixed α-helix and β-sheet structure .

ADA plays a pivotal role in maintaining the balance of purine nucleotides within the cell. By converting adenosine to inosine, ADA helps regulate the levels of adenosine, which can have various physiological effects, including modulation of the immune response .

Recombinant human ADA (rhADA) is produced using baculovirus expression systems in insect cells, such as Spodoptera frugiperda (Sf21) . The recombinant protein is often tagged with a histidine tag to facilitate purification and is supplied in a carrier-free formulation to avoid interference from other proteins .

ADA deficiency is a well-known cause of severe combined immunodeficiency (SCID), an autosomal recessive disorder characterized by a lack of functional T and B lymphocytes . Patients with ADA-SCID have undetectable levels of ADA activity, leading to the accumulation of toxic metabolites that impair lymphocyte development and function .

Recombinant ADA has been used as an enzyme replacement therapy for patients with ADA-SCID. This therapy involves the administration of polyethylene glycol (PEG)-modified ADA (PEG-ADA) to reduce the immunogenicity and prolong the half-life of the enzyme in the bloodstream .