The Entrapment of Polyethylene Glycol-Conjugated Adenosine Deaminase (Pegademase) and Native Adenosine Deaminase in Human Carrier Erythrocytes
Severe combined immunodeficiency (SCID) is a rare disorder with an incidence of 1:66 000. It is characterised by a defective humoral (hypogammaglobulinaemia) and cellular (lymphopenia) immunity and if untreated is severe and often lethal. Some 20% to 25% of SCID cases are due to a deficiency of adenosine deaminase (EC 22.214.171.124). Adenosine deaminase (ADA) is normally present in all mammalian cells and catalyses the deamination of adenosine and 2′-deoxyadenosine to inosine and 2′-deoxyinosine respectively for either salvage and re-utilisation or metabolism to uric acid and excretion. The major route of adenosine metabolism at physiological substrate levels is phosphorylation rather than deamination, this is because the K m for adenosine kinase (EC 126.96.36.199) is lower than that of ADA. Adenosine in excess of physiological levels is degraded by ADA. The major source of 2′-deoxyadenosine is DNA turnover and the main route of its metabolism is deamination by ADA.
KeywordsEnzyme Replacement Therapy Adenosine Deaminase Severe Combine Immunodeficiency Purine Nucleoside Phosphorylase Adenosine Deaminase Deficiency
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