Coordinacy of lysosomal enzyme excretion in human urine.

Paigen, Kenneth; Peterson, Janice

doi:10.1172/jci108989

Cited by 78 publications

(36 citation statements)

References 40 publications

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“…Exocytosis seems the most probable explanation (1). This phenomenon has been described in other mammalian cells (24) and has recently been proposed to explain the excretion oflysosomal hydrolases in human urine (25). Furthermore, there are morphologic studies indicating exocytic discharge of lysosomal contents in bile canaliculi (2-4, 26, 27).…”

Section: Discussionmentioning

confidence: 61%

Coordinate Secretion of Acid Hydrolases in Rat Bile

LaRusso¹,

Fowler²

1979

J. Clin. Invest.

102

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A B S T R A C T Three lysosomal glycosidases, j8-glucuronidase (EC 3.2.1.31), ,8-galactosidase (EC 3.2.1.23), and N-acetyl-,8-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-h 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 h of collection. 24-h biliary outputs of the three hydrolases averaged m3% 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 ofthe lysosomal hydrolases. Biliary excretion of total protein was relatively constant and corresponded to 3.0% ofthe total hepatic protein content per day, whereas biliary bile acid secretion decreased during the first 12 h 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.A preliminary report of part of this work appeared in 1977.

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Section: Discussionmentioning

confidence: 61%

Coordinate Secretion of Acid Hydrolases in Rat Bile

LaRusso¹,

Fowler²

1979

J. Clin. Invest.

102

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“…a-Glucosidase activity was measured in the medium and in the cell extract Activity added to medium Mannose Activity in 6-phosphate cells after in medium 24h source amount mU mM mU/mg protein Values are means of duplicate measurements in two separate preparations. In a parallel incubation a known amount of pure mannose 6-phosphate was subjected to the same procedure as the samples; the mannose 6-phosphate content decreased by 20 % [23] have found that several lysosomal enzymes are secreted into the urine in a coordinated fashion. The secretion of lysosomal enzymes is unrelated to that of the cytosolic enzyme lactate dehydrogenase, suggesting that the lysosomal enzymes found in the urine are not derived from exfoliated cells but are actively secreted.…”

Section: Purifcation Of Lysosomal A-glucosidase From Human Urinementioning

confidence: 99%

Isolation and characterization of a precursor form of lysosomal α‐glucosidase from human urine

Elferink

Brouwer-Kelder

Surya

et al. 1984

European Journal of Biochemistry

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1. A two‐step procedure is described for the isolation of lysosomal α‐glucosidase from human urine. In the second step, affinity chromatography on Sephadex G‐100, two fractions with acid α‐glucosidase activity were obtained. 2. Fraction I contained α‐glucosidase of Mr 109000, whereas fraction II contained components of Mr 76000 and 70000. 3. α‐Glucosidase in fraction I had an Mr similar to that of the precursor of α‐glucosidase detected in the medium of fibroblasts after labelling with [14C]leucine. The components in fraction II had Mr identical to those of the mature forms of α‐glucosidase found in placenta or cultured human skin fibroblasts. 4. α‐Glucosidase in fraction I contained mannose 6‐phosphate (3.5 mol/mol polypeptide). No mannose 6‐phosphate was present in the components in fraction II. 5. Fraction I, but not fraction II, was avidly endocytosed by α‐glucosidase‐deficient cultured human skin fibroblasts. Endocytosis of fraction I was inhibited by mannose 6‐phosphate. 6. The pH optimum and Km values for p‐nitrophenyl α‐glucoside, maltose and glycogen of fractions I and II α‐glucosidase were almost identical. However, the activity with glycogen relative to that of either p‐nitrophenyl α‐glucoside or maltose was lower in fraction I than in fraction II. 7. It is concluded that fraction I consists of the precursor form of α‐glucosidase and fraction II of the mature forms of the enzyme. 8. The importance of urine as a source of precursors of lysosomal enzymes is discussed.

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“…Due to this location of the B isoform (U-NAG-B), it is massively released in the tubular lumen only in the case of cytolytic tubular lesion. Its presence in the urine correlates with the cell lysis and is marked as lesion enzymuria [8,9]. NAG could also be detected in the circulation.…”

Section: Renal Markers For Estimation Of Renal Dysfunctionmentioning

confidence: 93%

“…Of all the urinary enzymes, U-NAG (urinary) has been extensively examined. It belongs to the class of hydrolases present in a large amount in the lysosomes in the proximal tubular cells [8]. In the human body and biological fluids there are two major enzyme forms: A (Acid) and B (Basic) [3][4][5].…”

Section: Renal Markers For Estimation Of Renal Dysfunctionmentioning

confidence: 99%

Some Aspects of Nephrotoxicity of Paracetamol and Ketoprofen in Patients with Rheumathoid Arthritis

Spasovski¹,

Genadieva-Stavric²,

Sotirova³

2016

Macedonian Medical Review

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Introduction. To determine the effect of initial therapy with Paracetamol and Ketoprofen on glomerular and tubular integrity in rheumatoid arthritis (RA), to quantify nephrotoxicity of these two drugs by measurement of enzymuria, which correlates with the damage of tubular epithelium. Microalbuminuria is used as a marker for glomerular damage, and urine excretion of N-Acetylb-D-glucosaminidase (NAG) as an indicator of proximal tubular damage. Methods. Using colorimetric method for determination of NAG, and immunoturbidimetric method for microalbuminuria, samples of 70 participants were examined (35 RA patients treated with Paracetamol only, 35 RA patients treated with Ketoprofen). The follow-up was in 5 time-intervals in the course of 24 weeks.Results. There was a moderate correlation between NAG and microalbuminuria (r=0.16) in the group of patients treated with Paracetamol only, and a moderate correlation (r=0.28) in the group of patients treated with Ketoprofen. NAG enzymuria in size, by number of patients Registered, and time of appearance, was greater and appeared earlier in the Ketoprofen group compared to the Paracetamol group. Conclusions. Ketoprofen is more potent NAG inductor and provokes greater tubular enzymuria than Paracetamol. Results from our study confirm safety in use of Paracetamol and Ketoprofen in everyday clinical practice.

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Coordinacy of lysosomal enzyme excretion in human urine.

Cited by 78 publications

References 40 publications

Coordinate Secretion of Acid Hydrolases in Rat Bile

Coordinate Secretion of Acid Hydrolases in Rat Bile

Isolation and characterization of a precursor form of lysosomal α‐glucosidase from human urine

Some Aspects of Nephrotoxicity of Paracetamol and Ketoprofen in Patients with Rheumathoid Arthritis

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