The reversible inhibition of β-glucuronidase by organic peroxides

Christner, James E.; Nand, S.; Mhatre, N.S.

doi:10.1016/0006-291x(70)90352-9

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…Gourley et al (3) have shown that 10 M saccharolactone will inhibit human milk ␤-glu by over 90%. Many other inhibitors of ␤-glu have been described and include an analog of nojirimycin (17), sumarin, alginic acid and particular polycarboxylic acids (13,18), sodium heparin (19), and organic peroxides (20). The general disadvantage of these inhibitors is that they are not compounds which, at significant concentrations, are safe dietary ingredients.…”

Section: Discussionmentioning

confidence: 99%

A Novel Inhibitor of β-Glucuronidase: l-Aspartic Acid

2001

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Infants who consume casein hydrolysate formula have been shown to have lower neonatal jaundice levels than infants who consume routine formula or breast milk. Because casein hydrolysate has been shown to contain a ␤-glucuronidase inhibitor, one possible mechanism to explain this finding is blockage of the enterohepatic circulation of bilirubin by a component of the formula. The aim of this research was to identify the source of the ␤-glucuronidase inhibition in hydrolyzed casein. A ␤-glucuronidase inhibition assay and measurements of physical and kinetic parameters were used to analyze the components of hydrolyzed casein and infant formulas. Kinetic studies used purified ␤-glucuronidase. The L-aspartic acid in hydrolyzed casein accounts for the majority of the ␤-glucuronidase inhibition present. Kinetic studies indicate a competitive inhibition mechanism. L-Aspartic acid is a newly identified competitive inhibitor of ␤-glucuronidase. NaAC, sodium acetate/acetic acid buffer, pH 4.5 SAB, sodium acetate/acetic acid buffer, pH 5.0 AMP, 100 mM 2-amino-2-methyl-1-propanol buffer containing 0.2% (wt/vol) sodium lauryl sulfate at pH 11.0 NRTU, Nutramigen ready-to-use formula EHC, enzymatically hydrolyzed casein NLFS, Nutramigen lipid-free supernatant PLFS, Phenyl-Free, lipid-free supernatant In 1992, the new finding that all neonatal formulas are not equal in their effect on neonatal jaundice was first reported. Infants who consumed a casein hydrolysate formula had lower levels of jaundice than infants who received routine (whey or casein predominant) infant formulas (1). This finding was subsequently confirmed in an independent study (2). A potential mechanism has been proposed and a causative factor has been identified that might explain this phenomenon. The enterohepatic circulation of bilirubin could be interrupted by a ␤-glu inhibitor present in enzymatically hydrolyzed casein (3). Bilirubin, arising mainly from the degradation of heme, undergoes hepatic conjugation with glucuronic acid and excretion as bilirubin glucuronides via bile into the intestine. Intestinal ␤-glu can cleave the glucuronide linkage to produce unconjugated bilirubin, which can be absorbed by the intestine back into the blood circulation (4). Inhibition of ␤-glu can block this enterohepatic circulation of bilirubin, thus facilitating fecal excretion and lower serum bilirubin concentration (5). Inhibitors of ␤-glu have also been suggested to have anticarcinogenic properties because they will increase clearance of glucuronidated carcinogens (6).Because neonatal jaundice is the most common cause for hospital readmission of neonates (7), any potential new therapeutic considerations are of interest. Identification of any ␤-glu inhibitor that is currently acknowledged to be a safe dietary element would be of considerable appeal. In this paper, data are presented which demonstrate that L-aspartic acid (L-asp) is one component of hydrolyzed casein infant formula that is inhibitory to ␤-glu. L-asp has not previously been identified as a ␤-glu inhibitor...

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Section: Discussionmentioning

confidence: 99%

A Novel Inhibitor of β-Glucuronidase: l-Aspartic Acid

2001

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“…have shown that 10 μM D‐saccharic acid‐1,4‐lactone can inhibit human milk β‐glucuronidase by over 90%. Many other inhibitors of β‐glucuronidase have been described, and include an analogue of nojirimycin, sumarin, alginic acid, and particular polycarboxylic acids, sodium heparin, and organic peroxides . The general disadvantage of these inhibitors is that they are not safe at higher concentrations .…”

Section: Introductionmentioning

confidence: 99%

Carbazole‐Linked 1,2,3‐Triazoles: In Vitro β‐Glucuronidase Inhibitory Potential, Kinetics, and Molecular Docking Studies

et al. 2019

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β‐Glucuronidase enzyme is a tetrameric glycoprotein present in microsomes and lysosomes of many organs, and body fluids. Over‐expression of this enzyme is observed in several melanomas and carcinomas. Therefore, it has been identified as a target for the treatment of several pathological conditions. In this regard, carbazole linked 1,2,3‐triazoles (1–27) were synthesized according to our previous report, and evaluated for their in vitro β‐glucuronidase inhibitory activities. Compounds 7–10, 17–18, 20, and 22–27 showed potent activities with IC50 values between 0.55–32.5 μM, as compared to the standard, D‐saccharic acid 1,4‐lactone (IC50=45.75 ± 2.16 μM). All active compounds were found to be non‐cytotoxic against mouse fibroblast 3T3 cell line. Compounds 20, 22, 23, 25, 26, and 27 were subjected to enzyme kinetic studies for the determination of their modes of inhibition, and dissociation constants Ki. Compounds 23, 25, and 26 were also studied for their mode of inhibition by using molecular docking methods.

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Malonal Generation Conditions of the Tobacco Smoke

Witas

Sledziewski

1980

Nahrung

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The possibility of malonic dia1dehyde.formation in the tobacco smoke was investigated and the conditions of the degree of malonal generation by smoke compounds were stated. The malonal concentration in smoke of cigarettes with filters is in the mean lower (28.7 mg/kg) than in smoke of cigarettes without filters (35.0 mg/ kg). The highest contents of malonal were received in "Zefir" (41.7 mgjkg), "Radomskie" (35.2 mg/kg) cigarettes with filters and "Sport" without filters (42.6 mg/kg) and by a half lower in "Giewont" cigarettes with filters (17.8 mg/kg).The tobacco smoke is a mixture of many volatile compounds, which are formed as a result of tobacco pyrolysis in the presence of oxygen or by its limited access. The very active compounds undergo continuous interreactions. In the pyrolisate fractions of the tobacco smoke, the groups of inactive, basic, acid and phenolic, simple and complex substances have been distinguished [17]. GROWER et al.[lo] and SIMS [28] consider oxides and peroxides of aromatic hydrocarbons responsible for biological changes in living organisms. BOGDER [2] notices the possibility to form polycyclic compounds from simple dicarbonic compounds by condensation.In an other group of works it is said, that intra-and intermolecular transverse couplings in biogenic food components and in living organisms are caused by malonic dialdehyde (malonal), which is formed either from oxidized unsaturated fatty acids and hydrocarbons or from saccharides 121, 221. Malorial, as very reactive tricarbonic compound inactivates among others substances such as lysine, methionine, histidine, glutathione, heme proteins, structured proteins and enzymes, e. g. ribonuclease A, cytochrome C, succinate oxidase, glucose-6-phosphate dehydrogenase, /?-glucuronidase and DNA, RNA and also a number of other compounds 13-8, 12, 13, 15-18,201. The malonylation of amino acids, proteins and enzymes causes forming of protein-fatty complexes of specific physicochemical and pathological properties [21].

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The reversible inhibition of β-glucuronidase by organic peroxides

Cited by 5 publications

References 11 publications

A Novel Inhibitor of β-Glucuronidase: l-Aspartic Acid

A Novel Inhibitor of β-Glucuronidase: l-Aspartic Acid

Carbazole‐Linked 1,2,3‐Triazoles: In Vitro β‐Glucuronidase Inhibitory Potential, Kinetics, and Molecular Docking Studies

Malonal Generation Conditions of the Tobacco Smoke

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