Enzymes and enzyme therapy

A large array of enzyme systems is present in the cell homogenates. Simpler artificial cells can be made to contain only one enzyme (Chang, 1964, 1972) (Fig. 2.3). The enclosed enzyme would not leak

Fig. 2.3. Upper left: Problems related to injection of enzymes in free solution. Upper right: Enzymes inside artificial cells no longer have these problems. Lower left: Artificial cells can be prepared with multistep enzyme systems with recyling of cofactors. Lower right: Nano artificial red cells contain all the enzymes of red blood cells.

Fig. 2.3. Upper left: Problems related to injection of enzymes in free solution. Upper right: Enzymes inside artificial cells no longer have these problems. Lower left: Artificial cells can be prepared with multistep enzyme systems with recyling of cofactors. Lower right: Nano artificial red cells contain all the enzymes of red blood cells.

out, but can act on external permeant substrates. This would avoid protein sensitization, anaphylactic reaction, or antibody production with repeated injections (Fig. 2.3). Implanted urease artificial cells convert systemic urea into ammonia (Chang, 1964, 1965). Implanting artificial cells containing catalase can replace the defective enzyme in mice with a congenital catalase defect — acatalasemia (Chang and Poznanski, 1968). The artificial cells protect the enclosed enzyme from immunological reactions (Poznanski and Chang, 1974). Artificial cells containing asparaginase implanted into mice delay the onset and growth of lymphosarcoma (Chang, 1971).

Giving enzyme artificial cells by mouth obviates the need for repeated injections. For example, artificial cells containing urease and ammonia adsorbent can lower the systemic urea level (Chang, 1972a). In Lesch-Nyhan disease, enzyme defect resulted in the elavation of hypoxanthine to toxic levels. Given by mouth, artificial cells containing xanthine oxidase lowers the toxic systemic hypoxanthine levels in an infant with this disease (Chang, 1989; Palmour et al., 1989). Phenylketonuria is a more common congenital enzyme defect. Artificial cells containing phenylalanine ammonia lyase, given by mouth, lower the systemic phenylalanine levels in phenylketonuria [PKU] in rats (Bourget and Chang, 1986). This leads to investigation into recombinant sources of this enzyme (Sarkissian et al., 1999; Liu et al., 2002).

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