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 184.108.40.206). 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 220.127.116.11) 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
Unable to display preview. Download preview PDF.
- Herschfield, M.S. Enzyme replacement therapy of adenosine deaminase deficiency with polyethylene glycolmodified adenosine deaminase (PEG-ADA). Immunodefic. 4: 93–97 (1993).Google Scholar
- Herschfield, M.S. and Mitchell, B.S. Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. In The Molecular and Metabolic Basis of Inherited Disease (ed. Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D.) Vol. II, pp1725–1768, McGraw-Hill, New York (1995).Google Scholar
- Simmonds, H.A. Purine and pyrimidine disorders. In The Inherited Metabolic Diseases. (ed. Holton, J.B.) pp 297-349., Churchill Livingstone, Edinburgh (1994).Google Scholar
- Sprandel, U., Hubbard, A.R. and Chalmers, R.A. Survival of ‘carrier erythrocytes’ in dogs. Clin. Sci. 59: 7P (1980).Google Scholar