β‐Glucosidase activity towards a bile acid glucoside in human liver

Matern, Heidrun; Gartzen, R.; Matern, Siegfried

doi:10.1016/0014-5793(92)80970-r

Cited by 16 publications

(23 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other minor ␤-glucosidases in addition to the cytosolic and lysosomal forms have been described. These enzymes include a membrane-associated, nonlysosomal glucosylceramidase, 29 a bile salt ␤-glucosidase localized to the microsomes, 30 and a novel lysosomal ␤-glucosidase that is specific for 6-acylamino-4-methylumbelliferyl-␤-D-glucosides. 31 In the absence of inhibitors specific for each of these enzymes, we cannot exclude their participation in the hydrolysis of RESGlc in situ.…”

Section: Discussionmentioning

confidence: 99%

Expression of cytosolic β-glucosidase in guinea pig liver cells

et al. 1998

View full text Add to dashboard Cite

The cytosolic ␤-glucosidase of mammalian liver has been implicated in the metabolic transformation of plant glycosides, such as vicine and amygdalin, which are associated with the development of toxic syndromes. We investigated which cell types express cytosolic ␤-glucosidase in guinea pig liver, and characterized the contribution of this enzyme to the hydrolysis of aromatic glucosides in cultured cells and in tissue slices. Cytosolic ␤-glucosidase was expressed in hepatocytes and not in Kupffer or endothelial cells as determined by enzyme-specific activity and Western blots of liver cell extracts. Intracellular ␤-glucosidase activity was visualized using the fluorescent ␤-glucosidase substrate, resorufin ␤-D-glucoside, and shown to be caused by the cytosolic ␤-glucosidase using the inhibitors, conduritol ␤-epoxide and dinitrophenol-2-deoxy-2-fluoro-␤-D-glucopyranoside (DNP2FGlc). Staining of fresh liver slices with resorufin ␤-glucoside revealed that cytosolic ␤-glucosidase is expressed in all hepatocytes, with no significant portalcentral gradient. These data indicate that cytosolic ␤-glucosidase is a hepatocyte-specific enzyme, and support the hypothesis that cytosolic ␤-glucosidase in the liver functions to hydrolyze small glucosides absorbed by the intestine. Furthermore, toxic injury to cultured hepatocytes by CCl 4 resulted in release of cytosolic ␤-glucosidase in parallel with the hepatocyte marker enzymes alanine transaminase and lactate dehydrogenase. This suggests that acute increases in serum levels of cytosolic ␤-glucosidase in animal models of liver injury may reflect direct injury of hepatocytes. (HEPATOLOGY 1998;28:156-163.)A principal physiological function of the liver is to dispose of xenobiotic compounds absorbed from the intestinal tract. The detoxification and excretion pathways for numerous compounds are classified into two stages. Phase I reactions involve either oxidation or reduction reactions, and are typically catalyzed by cytochrome P450 enzymes. 1 Phase II reactions then conjugate the modified compound, typically with glucuronic acid, sulfate, or glutathione, before excretion of the conjugate into the bile. 2 In plants, however, a variety of physiologically relevant compounds are produced and stored as O-linked ␤-D-glucosides. 3-5 Although the metabolic disposal of such glucosides by mammals is largely uncharacterized, it is likely that removal of the glucose moiety occurs at some point before ultimate excretion. Furthermore, the aglycone moieties of ␤-D-glucosides found in dietary plants have been implicated as the etiologic agents in acute cyanide intoxication resulting from ingestion of cassava, 6 apricot seeds, 7 and administration of amygdalin (laetrile), 8 as well as neurodegenerative disorders such as western pacific amyotrophic lateral sclerosis/parkinsonism-dementia. 6 The cytosolic ␤-glucosidase of mammalian liver has been characterized and studied by several groups. 9 The enzyme has been described in the livers of humans, 10 cattle, 11 rabbits, 12 and guinea pigs. 13 Cyto...

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of cytosolic β-glucosidase in guinea pig liver cells

et al. 1998

View full text Add to dashboard Cite

show abstract

“…The bile acid glucosidase activity of GBA2 is inhibited by iminosugars such as 1-deoxynojirimycin (10,12), and administration of alkylated iminosugars to mice causes male infertility and globozoospermia (22)(23)(24). 1-Deoxynojirimycin inhibits glucosidases involved in the processing of asparagine-linked carbohydrates attached to proteins as well as those involved in the biosynthesis of glycolipids (25,26).…”

Section: Figurementioning

confidence: 99%

“…causes globozoospermia when administered to rodents (22), male patients with Gaucher's disease who receive the drug are advised to take appropriate birth control measures. Given the expression of GBA2 in the Sertoli cells of wild-type mouse testis, the presence of globozoospermia in the GBA2 knockout mice, and the ability of alkylated deoxynojirimycin derivatives to inhibit the GBA2 enzyme (10,12), it is possible that inhibition of testicular GBA2 rather than glucosylceramide synthetase underlies this side effect in subjects with Gaucher's disease. If this hypothesis is correct, then more selective inhibitors of the glucosylceramide synthetase may be useful in the treatment of Gaucher's disease, while GBA2-specific inhibitors may be useful as male contraceptives.…”

Section: Figurementioning

confidence: 99%

“…Bile acid glucosidase and transferase activities were determined as described previously (10,16). Glucosylceramidase activity was assessed as described previously (29).…”

Section: Construction Of Gba2 Knockout Mouse a Targeting Vector Compmentioning

confidence: 99%

“…GBA1 is distinguished from other O-glycosyl hydrolases by an acidic pH optimum and a preference for glycolipids. A second hydrolase with these general properties is β-glucosidase 2 (GBA2), a membrane-bound enzyme of the ER that is active in both the cleavage and the formation of bile acid glucosides and is inhibited by alkyl-deoxynojirimycin derivatives (10)(11)(12)(13). Bile acid glucosides, in which glucose is attached in β-linkage to carbon 3 of the bile acid (14), are normally excreted in the urine (15).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mutation of β-glucosidase 2 causes glycolipid storage disease and impaired male fertility

Yildiz¹,

Matern²,

Thompson³

et al. 2006

J. Clin. Invest.

202

231

View full text Add to dashboard Cite

β-Glucosidase 2 (GBA2) is a resident enzyme of the endoplasmic reticulum thought to play a role in the metabolism of bile acid-glucose conjugates. To gain insight into the biological function of this enzyme and its substrates, we generated mice deficient in GBA2 and found that these animals had normal bile acid metabolism. Knockout males exhibited impaired fertility. Microscopic examination of sperm revealed large round heads (globozoospermia), abnormal acrosomes, and defective mobility. Glycolipids, identified as glucosylceramides by mass spectrometry, accumulated in the testes, brains, and livers of the knockout mice but did not cause obvious neurological symptoms, organomegaly, or a reduction in lifespan. Recombinant GBA2 hydrolyzed glucosylceramide to glucose and ceramide; the same reaction catalyzed by the β-glucosidase acid 1 (GBA1) defective in subjects with the Gaucher's form of lysosomal storage disease. We conclude that GBA2 is a glucosylceramidase whose loss causes accumulation of glycolipids and an endoplasmic reticulum storage disease.

show abstract

Inhibition of cholesterol biosynthesis in HepG2 cells by artichoke extracts is reinforced by glucosidase pretreatment

Gebhardt

2002

Phytotherapy Research

View full text Add to dashboard Cite

High-dose aqueous extracts from artichoke leaves were found to inhibit cholesterol biosynthesis from (14)C-acetate rather moderately in HepG2 cells in contrast to primary cultured rat hepatocytes in which the inhibition was stronger. Preincubation of the extracts with several glycohydrolases revealed that pretreatment with beta-glucosidase considerably reinforced the inhibition. A significant reduction of acetate incorporation was found above extract concentrations of 0.01 mg/mL and at 0.2 mg/mL almost 60% inhibition was observed. Cytotoxic effects detected by the MTT-assay were restricted to higher concentrations of the extracts with and without beta-glucosidase pretreatment. Since cynaroside represents a major glucoside in artichoke extracts, both cynaroside and its aglycone luteolin were tested. It could be demonstrated that cynaroside is indeed one of the targets of beta-glucosidase and that the liberated luteolin is responsible for the inhibitory effect. Direct measurements of beta-glucosidase activity in rat hepatocytes and HepG2 cells revealed that endogenous enzyme activity in hepatocytes may be sufficient to convert cynaroside to its aglycone, while in HepG2 cells this may not be the case. These findings emphasize the importance of beta-glucosidase-dependent liberation of luteolin for the ability of artichoke extracts to inhibit hepatic cholesterol biosynthesis.

show abstract

β‐Glucosidase activity towards a bile acid glucoside in human liver

Cited by 16 publications

References 19 publications

Expression of cytosolic β-glucosidase in guinea pig liver cells

Expression of cytosolic β-glucosidase in guinea pig liver cells

Mutation of β-glucosidase 2 causes glycolipid storage disease and impaired male fertility

Inhibition of cholesterol biosynthesis in HepG2 cells by artichoke extracts is reinforced by glucosidase pretreatment

Contact Info

Product

Resources

About