Factors that Influence the Uptake and Turnover of Glucocerebrosidase and α-Galactosidase in Mammalian Liver

Abstract

Recent studies have revealed the potential therapeutic effectiveness of highly purified human glucocerebrosidase in Gaucher’s disease and α-galactosidase in Fabry’s disease (1–3). The rationale underlying these investigations was that supplementation of the specific enzyme deficiencies that occur in such genetic lysosomal storage disorders might reverse the accumulation of toxic metabolites. The initial studies indicate that infusion of the requisite enzyme specifically reduced the elevated level of these respective glycolipidsin the circulation and/or tissue in these disorders. In order to extend these investigations profitably, it was important to obtain detailed information concerning the behavior of the infused enzymes in vivo. In the present investigation, we examined the hepatic uptake and turnover of glucocerebrosidase and α-galactosidase in monkeys and rats. We have discovered several important factors that significantly influence these processes. These observations and the notable differences in the metabolism of the two enzymes are described in this report.