Presence and absence of the microsomal beta-glucuronidase in mice correlates with differences in the processing of the lysosomal enzyme.

In some tissues such as liver and kidney, beta-glucuronidase is present not only in the lysosomes but also in the microsomes. Both enzymes are coded by the same structural gene. The function of the microsomal enzyme is still unclear. We have observed in primary cultures of mouse hepatocytes that the microsomal enzyme disappeared to a trace within 5 days after plating cells. This change of intracellular localization coincided with a change of the isoelectric focusing pattern of the lysosomal beta-glucuronidase. Within the multiple banding pattern of the lysosomal enzyme, a faintly staining group of bands in the more acidic range (mean pI 5.4) became more pronounced while a major group (mean pI 5.9) faded slightly. The correlation between the presence or absence of the microsomal beta-glucuronidase and distinct proportions of the two lysosomal enzyme forms was confirmed in vivo. The less acidic form (pI 5.9) prevailed in the presence (kidney, liver), the more acidic form (pI 5.4) in the absence of the microsomal enzyme (spleen). The two lysosomal forms differed also in their apparent molecular weight by approx. 1500 (Mr 71 500 versus 73 000). In order to elucidate the biosynthetic relationship between the microsomal enzyme and the two lysosomal enzyme forms we interfered with their processing in cultured hepatocytes. The addition of the protease/esterase inhibitor phenyl-methyl-sulfonyl-fluoride caused the disappearance of the microsomal and the appearance of the acidic pI 5.4 lysosomal enzyme within 24 h; with chloroquine, the microsomal enzyme remained nd no lysosomal pI 5.4 enzyme appeared.(ABSTRACT TRUNCATED AT 250 WORDS)