Enzyme Activities in Human Liver

1970 ◽  
Vol 11 (1-2) ◽  
pp. 67-129 ◽  
Author(s):  
E. Schmidt ◽  
F.W. Schmidt
Keyword(s):  
Enzyme Activities ◽  
Human Liver

Interaction of isoflavonoids with human liver microsomal cytochromes P450: inhibition of CYP enzyme activities

Xenobiotica ◽  
2016 ◽  
Vol 47 (4) ◽  
pp. 324-331 ◽  
Author(s):  
Michaela Kopečná-Zapletalová ◽  
Kristýna Krasulová ◽  
Pavel Anzenbacher ◽  
Petr Hodek ◽  
Eva Anzenbacherová
Keyword(s):  
Enzyme Activities ◽  
Human Liver ◽  
Cytochromes P450

scholarly journals AM-2201 Inhibits Multiple Cytochrome P450 and Uridine 5′-Diphospho-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

Molecules ◽  
2017 ◽  
Vol 22 (3) ◽  
pp. 443 ◽  
Author(s):  
Ju-Hyun Kim ◽  
Soon-Sang Kwon ◽  
Tae Kong ◽  
Jae Cheong ◽  
Hee Kim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Enzyme Activities ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes

Rapid determination of enzyme activities of recombinant human cytochromes P450, human liver microsomes and hepatocytes

2003 ◽  
Vol 24 (9) ◽  
pp. 375-384 ◽  
Author(s):  
Anima Ghosal ◽  
Neil Hapangama ◽  
Yuan Yuan ◽  
Xiaowen Lu ◽  
Debra Horne ◽  
...  
Keyword(s):  
Enzyme Activities ◽  
Human Liver ◽  
Rapid Determination ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Human Liver Microsomes

scholarly journals Mertansine Inhibits mRNA Expression and Enzyme Activities of Cytochrome P450s and Uridine 5′-Diphospho-Glucuronosyltransferases in Human Hepatocytes and Liver Microsomes

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 220
Author(s):  
Won-Gu Choi ◽  
Ria Park ◽  
Dong Kyun Kim ◽  
Yongho Shin ◽  
Yong-Yeon Cho ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Enzyme Activities ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Hepatocytes ◽  
Cytochrome P450s ◽  
Human Liver Microsomes ◽  
Mrna Levels ◽  
Tubulin Inhibitor

Mertansine, a tubulin inhibitor, is used as the cytotoxic component of antibody–drug conjugates (ADCs) for cancer therapy. The effects of mertansine on uridine 5′-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes and its effects on the mRNA expression of cytochrome P450s (CYPs) and UGTs in human hepatocytes were evaluated to assess the potential for drug–drug interactions (DDIs). Mertansine potently inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-β-glucuronidation, and UGT1A4-catalyzed trifluoperazine N-β-d-glucuronidation, with Ki values of 13.5 µM, 4.3 µM, and 21.2 µM, respectively, but no inhibition of UGT1A6, UGT1A9, and UGT2B7 enzyme activities was observed in human liver microsomes. A 48 h treatment of mertansine (1.25–2500 nM) in human hepatocytes resulted in the dose-dependent suppression of mRNA levels of CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGT1A1, and UGT1A9, with IC50 values of 93.7 ± 109.1, 36.8 ± 18.3, 160.6 ± 167.4, 32.1 ± 14.9, 578.4 ± 452.0, 539.5 ± 233.4, 856.7 ± 781.9, and 54.1 ± 29.1 nM, respectively, and decreased the activities of CYP1A2-mediated phenacetin O-deethylase, CYP2B6-mediated bupropion hydroxylase, and CYP3A4-mediated midazolam 1′-hydroxylase. These in vitro DDI potentials of mertansine with CYP1A2, CYP2B6, CYP2C8/9/19, CYP3A4, UGT1A1, and UGT1A9 substrates suggest that it is necessary to carefully characterize the DDI potentials of ADC candidates with mertansine as a payload in the clinic.

Enzyme Activities in Human Liver Biopsies: Assay Methods and Activities of Some Lysosomal and Membrane-Bound Enzymes in Control Tissue and Serum

1977 ◽  
Vol 52 (3) ◽  
pp. 229-239 ◽  
Author(s):  
Carol A. Seymour ◽  
T. J. Peters
Keyword(s):  
Enzyme Activities ◽  
Needle Biopsy ◽  
Human Liver ◽  
Acid Hydrolases ◽  
Highly Sensitive ◽  
Human Liver Biopsies ◽  
Membrane Bound ◽  
Assay Methods ◽  
Liver Biopsies ◽  
Membrane Bound Enzymes

1. Highly sensitive techniques are described for the assay of plasma membrane (5′-nucleotidase, alkaline phosphatase), microsomal (neutral α-glucosidase, leucyl-2-naphthylamidase) and biliary canalicular (γ-glutamyltransferase) enzymes and for nine acid hydrolases (acid phosphatase, phosphodiesterase, β-glucosidase, α-glucosidase, α-galactosidase, β-galactosidase, α-mannosidase, N-acetyl-β-glucosaminidase, β-glucuronidase) in human liver. 2. Optimum and specific assay systems have been developed which give linear kinetics for all enzymes. 3. The range of enzyme activities in samples of human liver, obtained by closed needle biopsy, and in sera have been determined.

scholarly journals Human α-l-iduronidase. Catalytic properties and an integrated role in the lysosomal degradation of heparan sulphate

1992 ◽  
Vol 282 (3) ◽  
pp. 899-908 ◽  
Author(s):  
C Freeman ◽  
J J Hopwood
Keyword(s):  
Enzyme Activity ◽  
Enzyme Activities ◽  
Human Liver ◽  
Skin Fibroblast ◽  
Catalytic Properties ◽  
Heparan Sulphate ◽  
Structural Features ◽  
Lysosomal Degradation ◽  
Catalytic Activities ◽  
Wide Range

The kinetic parameters (Km and kcat) of human liver alpha-L-iduronidase were determined with a variety of heparin-derived disaccharide and tetrasaccharide substrates. More structurally complex substrates, in which several aspects of the aglycone structure of the natural substrates heparin and heparan sulphate were maintained, were hydrolysed with catalytic efficiencies up to 255 times that observed for the simplest disaccharide substrate to be hydrolysed. The major aglycone structure that influenced both substrate binding and enzyme activity was the presence of a C-6 sulphate ester on the residue adjacent to the iduronic acid residue being hydrolysed. Sulphate ions and a number of substrate and product analogues were potent inhibitors of enzyme activity. Human liver alpha-L-iduronidase activity towards 4-methylumbelliferyl alpha-L-iduronide at pH 4.8 had two Km values of 37 microM and 1.92 mM with corresponding kcat. values of 299 and 650 mol of product formed/min per mol of enzyme respectively, which may explain the wide range of Km values previously reported for alpha-L-iduronidase activity toward its substrate. Skin fibroblast alpha-L-iduronidase activity towards the heparin-derived oligosaccharides was influenced by the same substrate aglycone structural features as was observed for the human liver enzyme. A comparison was made of the effect of substrate aglycone structure upon catalytic activities of the enzymes which act to degrade the highly sulphated regions of heparan sulphate. A model was proposed whereby the substrate is directed from alpha-L-iduronidase to subsequent enzyme activities to ensure the efficient degradation of heparan sulphate.

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