Synthesis and turnover of lysosomal glycoproteins. Relation to the molecular heterogeneity of the lysosomal enzymes

Abstract

Many, if not all, of the lysosomal acid hydrolases exist in several molecular forms. For example, using polyacrylamide gel electrophoresis [l] and isoelectric focusing [2,3] we found two to five distinct forms of seven different hydrolases in rat kidney lysosomes. That this molecular heterogeneity may have biological importance is strongly suggested by the recent discovery that the acidic (A) form of a lysosomal hydrolase is lacking in two inherited lipid storage diseases, namely aryl sulfatase A in metachromatic leukodystrophy [4,5] and hexosaminidase A in TaySachs disease [6,7] . Apparently the corresponding basic (B) form of these hydrolases which is present in normal or elevated amounts in these diseases is incapable of hydrolyzing the accumulated sphingolipid, cerebroside sulfate in metachromatic leukodystrophy [4,5] and GM, ganglioside (and its asialo derivative) in Tay-Sachs disease [6,7] . These observations imply that the different molecular forms may display divergent substrate specificities and hydrolytic activities in vivo. We have shown that the various acid hydrolases in purified lysosomal fractions from rat kidney and liver are glycoproteins (GPs) [ 1,8,9] . A study of the effects of bacterial neuraminidase on the electrophoretic mobility [8] , and pIs [3] of a number of lysosomal hydrolases indicated that N-acetylneuraminic acid (NANA) residues are largely responsible for the solubility and electronegative charge of these enzymes. On the basis of the solubility and electrophoretic mobility of five acid hydrolases in rat kidney subcellular fractions [9, lo] , and