Coordinate secretion of acid hydrolases in rat bile. Hepatocyte exocytosis of lysosomal protein?

N. F. LaRusso, S. Fowler

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Three lysosomal glycosidases, β-glucuronidase (EC 3.2.1.31), β-galactosidase (EC 3.2.1.23), and N-acetyl-β-glucosaminidase (EC 3.2.1.30) have been investigated in bile that was freshly collected from rats through a complete bile fistula. Assay conditions have been established on the basis of appropriate kinetic studies. The biliary excretion patterns for these enzymes were found to vary considerably from rat to rat during the 24-hr collection period. In a given animal, however, the three hydrolases were excreted in parallel and showed a gradual increase in activity with time, most marked after 10-12 hr of collection. 24-hr biliary outputs of the three hydrolases averaged ≃ 3% of their respective contents in total liver, and bile diversion had no effect on hepatic glycosidase activity or total protein content. Other enzymes known to be associated primarily with mitochondria, endoplasmic reticulum, and cell sap were also detected in bile, generally in smaller amounts. The biliary excretion of the plasma membrane markers, alkaline phosphodiesterase I and 5'-nucleotidase, however, was comparable to that of the lysosomal hydrolases. Biliary excretion of total protein was relatively constant and corresponded to 3.0% of the total hepatic protein content per day, whereas biliary bile acid secretion decreased during the first 12 hr and then remained constant. Exocytic bulk discharge of hepatocyte lysosomes is proposed as the most likely mechanism for the biliary excretion of lysosomal enzymes. These results call attention to the possible pathophysiologic significance of biliary excretion of hepatic lysosomal contents as a means of residue disposal.

Original languageEnglish (US)
Pages (from-to)948-954
Number of pages7
JournalJournal of Clinical Investigation
Volume64
Issue number4
DOIs
StatePublished - 1979

ASJC Scopus subject areas

  • Medicine(all)

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