scholarly journals Substrate Specificity and Ligand Interactions of CYP26A1, the Human Liver Retinoic Acid Hydroxylase

2011 ◽  
Vol 80 (2) ◽  
pp. 228-239 ◽  
Author(s):  
Jayne E. Thatcher ◽  
Brian Buttrick ◽  
Scott A. Shaffer ◽  
Jakob A. Shimshoni ◽  
David R. Goodlett ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Substrate Specificity ◽  
Human Liver ◽  
Ligand Interactions

scholarly journals Substrate specificity of human liver neutral α-mannosidase

1992 ◽  
Vol 286 (1) ◽  
pp. 47-53 ◽  
Author(s):  
S al Daher ◽  
R De Gasperi ◽  
P Daniel ◽  
S Hirani ◽  
C Warren ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Human Liver ◽  
Core Structure ◽  
Catabolic Pathways ◽  
Mannose Residue ◽  
The Core ◽  
High Mannose

The digestion of radiolabelled natural oligosaccharide substrates by human liver neutral alpha-mannosidase has been studied by h.p.l.c. and h.p.t.l.c. The high-mannose oligosaccharides Man9GlcNAc and Man8GlcNAc are hydrolysed by the enzyme by two distinct non-random routes to a common product of composition Man6GlcNAc, which is then slowly converted into a unique Man5GlcNAc oligosaccharide, Man alpha(1----2)Man alpha(1----2)Man alpha(1----3)[Man alpha (1----6)] Man beta(1----4)GlcNAc. These pathways are different from the processing and lysosomal catabolic pathways for these structures. In particular, the alpha(1----2)-linked mannose residues attached to the core alpha(1----3)-linked mannose residue are resistant to hydrolysis. The key processing intermediate, Man alpha(1----3)[Man alpha(1----6)]Man alpha(1----6)[Man alpha(1----3)] Man beta(1----4)GlcNAc, is not produced in the digestion of high-mannose glycans by the neutral alpha-mannosidase, but it is hydrolysed by the enzyme by a non-random route to Man beta(1----4)GlcNAc via the core structure Man alpha(1----3)[Man alpha(1----6)]Man beta(1----4)GlcNAc. In contrast with its ready hydrolysis by lysosomal alpha-mannosidase, the core alpha(1----3)-mannosidic linkage is quite resistant to hydrolysis by neutral alpha-mannosidase. The precise specificity of neutral alpha-mannosidase towards high-mannose oligosaccharides suggests that it has a role in the modification of such structures in the cytosol.

scholarly journals Purification and Cloning of a Broad Substrate Specificity Human Liver Carboxylesterase That Catalyzes the Hydrolysis of Cocaine and Heroin

1997 ◽  
Vol 272 (23) ◽  
pp. 14769-14775 ◽  
Author(s):  
Evgenia V. Pindel ◽  
Natalia Y. Kedishvili ◽  
Trent L. Abraham ◽  
Monica R. Brzezinski ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Human Liver ◽  
Broad Substrate Specificity ◽  
Hydrolysis Of

scholarly journals Cellular localization and substrate specificity of isoelectric forms of human liver neuraminidase activity

1987 ◽  
Vol 241 (1) ◽  
pp. 137-143 ◽  
Author(s):  
J Spaltro ◽  
J A Alhadeff
Keyword(s):  
Plasma Membrane ◽  
Substrate Specificity ◽  
Isoelectric Focusing ◽  
Human Liver ◽  
Cellular Localization ◽  
Human Liver Tissue ◽  
Neuraminidase Activity ◽  
Acetylneuraminic Acid ◽  
Acidic Form ◽  
Hydrolysis Of

The four major isoelectric forms of human liver neuraminidase (with pI values between 3.4 and 4.8) have been isolated by preparative isoelectric focusing and characterized with regard to their substrate specificity using glycoprotein, glycopeptide, oligosaccharide and ganglioside natural substrates. All forms exhibited a rather broad linkage specificity and were capable of hydrolyzing sialic acid glycosidically linked alpha 2-3, alpha 2-6 and alpha 2-8, although differential rates of hydrolysis of the substrates were found for each form. The most acidic form 1 (pI 3.4) was most active on sialyl-lactose, whereas form 2 (pI 3.9) and 3 (pI 4.4) were most active on the more hydrophobic ganglioside substrates. Form 4 (pI 4.8) was most active on the low-Mr hydrophilic substrates (fetuin glycopeptide, sialyl-lactose). Each form was less active on the glycoprotein fetuin than on a glycopeptide derived from fetuin. Organelle-enriched fractions were prepared from fresh human liver tissue and neuraminidase activity on 2′-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid was recovered in plasma membrane, microsomal, lysosomal and cytosolic preparations. Isoelectric focusing of the neuraminidase activity recovered in each of these preparations resulted in significantly different isoelectric profiles (number, relative amounts and pI values of forms) for each preparation. The differential substrate specificity of the isoelectric forms and the different isoelectric focusing profiles of neuraminidase activity recovered in subcellular-enriched fractions suggest that specific isoelectric forms with broad but defined substrate specificity are enriched at separate sites within the cell.

scholarly journals Development and Characterization of Novel and Selective Inhibitors of Cytochrome P450 CYP26A1, the Human Liver Retinoic Acid Hydroxylase

2016 ◽  
Vol 59 (6) ◽  
pp. 2579-2595 ◽  
Author(s):  
Philippe Diaz ◽  
Weize Huang ◽  
Charles M. Keyari ◽  
Brian Buttrick ◽  
Lauren Price ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Human Liver ◽  
Selective Inhibitors

scholarly journals Identification of human cytochromes P-450 analogous to forms induced by phenobarbital and 3-methylcholanthrene in the rat

1985 ◽  
Vol 232 (3) ◽  
pp. 869-876 ◽  
Author(s):  
D J Adams ◽  
S Seilman ◽  
Z Amelizad ◽  
F Oesch ◽  
C R Wolf
Keyword(s):  
Substrate Specificity ◽  
Rat Liver ◽  
Human Liver ◽  
Western Blots ◽  
Human Samples ◽  
Human Proteins ◽  
Related Proteins ◽  
Cytochrome P 450 ◽  
Antibody Inhibition

Antibodies to four rat liver forms of cytochrome P-450, two phenobarbital-inducible (PB1 and PB2) and two 3-methylcholanthrene-inducible (MC1 and MC2) proteins, have been used to make a structural and functional comparison of rat and human cytochromes P-450. Proteins from both species were identified on Western blots by their reaction with these antibodies. In the human liver preparations, structurally related proteins to PB1 and to PB2 were identified in all the samples tested with apparent Mr values of 51 800 and 54 800 for PB1 and 53 600 and 57 200 for PB2. Considerable variation in the content of the lower-Mr proteins was measured between samples and, as with the rat enzymes, samples which reacted well with anti-PB1 also reacted with anti-PB2, indicating that these proteins are regulated at least to some degree, co-ordinately. The apparent Mr values of the major human proteins identified with anti-MC1 and anti-MC2 were 54 400 and 57 000 respectively. Only six (of 31) human samples contained significant amounts of these proteins. The same six samples which reacted with anti-MC1 also reacted with anti-MC2, again indicating co-ordinate regulation of these two proteins. Antibody inhibition of microsomal 7-ethoxycoumarin and 7-ethoxyresorufin metabolism demonstrated a degree of conservation of substrate specificity related to specific P-450 isoenzymes between the species. However, the contributions of the different P-450 isoenzymes to the human microsomal activity were not always related to the rat enzyme with the highest activity towards these substrates.

scholarly journals Substrate specificity of a thymidine phosphorylase in human liver tumor.

1984 ◽  
Vol 32 (5) ◽  
pp. 1919-1921 ◽  
Author(s):  
AKIRA KONO ◽  
YASUHIRO HARA ◽  
SETSURO SUGATA ◽  
YOSHIKAZU MATSUSHIMA ◽  
TOHRU UEDA
Keyword(s):  
Substrate Specificity ◽  
Liver Tumor ◽  
Human Liver ◽  
Thymidine Phosphorylase

Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver

Hepatology ◽  
1997 ◽  
Vol 26 (6) ◽  
pp. 1667-1677 ◽  
Author(s):  
P J Meier ◽  
U Eckhardt ◽  
A Schroeder ◽  
B Hagenbuch ◽  
B Stieger
Keyword(s):  
Bile Acid ◽  
Substrate Specificity ◽  
Human Liver ◽  
Organic Anion ◽  
Anion Uptake

scholarly journals Purification and characterization of a rat brain aldehyde dehydrogenase able to metabolize γ-aminobutyraldehyde to γ-aminobutyric acid

1990 ◽  
Vol 269 (1) ◽  
pp. 25-29 ◽  
Author(s):  
T Abe ◽  
K Takada ◽  
K Ohkawa ◽  
M Matsuda
Keyword(s):  
Substrate Specificity ◽  
Rat Brain ◽  
Aldehyde Dehydrogenase ◽  
Human Liver ◽  
Alternative Pathway ◽  
Deae Cellulose ◽  
Aminobutyric Acid ◽  
Mammalian Brain ◽  
Aldehyde Dehydrogenases ◽  
Brain Tissues

An enzyme which catalyses dehydrogenation of gamma-aminobutyraldehyde (ABAL) to gamma-aminobutyric acid (GABA) was purified to homogeneity from rat brain tissues by using DEAE-cellulose and affinity chromatography on 5′-AMP-Sepharose, phosphocellulose and Blue Agarose, followed by gel filtration. Such an enzyme was first purified from mammalian brain tissues, and was identified as an isoenzyme of aldehyde dehydrogenase. It has an Mr of 210,000 determined by polyacrylamide-gradient-gel electrophoresis, and appeared to be composed of subunits of Mr 50,000. The close similarity of substrate specificity toward acetaldehyde, propionaldehyde and glycolaldehyde between the enzyme and other aldehyde dehydrogenases previously reported was observed. But substrate specificity of the enzyme toward ABAL was higher than those of aldehyde dehydrogenases from human liver (E1 and E2), and was lower than those of ABAL dehydrogenases from human liver (E3), Escherichia coli and Pseudomonas species. The Mr and relative amino acid composition of the enzyme are also similar to those of E1 and E2. The existence of this enzyme in mammalian brain seems to be related to a glutamate decarboxylase-independent pathway (alternative pathway) for GABA synthesis from putrescine.

scholarly journals Haemoglobin-catalysed retinoic acid 5,6-epoxidation

1985 ◽  
Vol 232 (2) ◽  
pp. 459-466 ◽  
Author(s):  
H Iwahashi ◽  
A Ikeda ◽  
R Kido
Keyword(s):  
Retinoic Acid ◽  
Rat Liver ◽  
Human Blood ◽  
Blood Cells ◽  
Human Liver ◽  
Inhibitory Effect ◽  
Human Haemoglobin ◽  
Haemoglobin Solution ◽  
Liver Homogenates ◽  
Residual Blood

Examination of the subcellular distribution of retinoic acid 5,6-epoxidase activity in rat liver and human liver homogenates showed that there is a prominent peak of activity in a high-density fraction. A corresponding peak was also detected in rat blood and human blood. Retinoic acid 5,6-epoxidation was catalysed by human blood cells but not by human plasma, and purified human haemoglobin also catalysed the epoxidation of retinoic acid to 5,6-epoxyretinoic acid. These results suggest that retinoic acid 5,6-epoxidase activity in human liver and rat liver homogenates is partially due to the presence of residual blood cells, and particularly haemoglobin, in the homogenates. In the retinoic acid 5,6-epoxidation catalysed by human haemoglobin, molecular O2 was required and its reaction was stimulated by Triton X-100. Boiling of haemoglobin solution resulted in an 94% decrease in the activity. NADPH (1 mM) and NADH (1 mM) completely [2-mercaptoethanol (5 mM) almost completely] inhibited the 5,6-epoxidation catalysed by haemoglobin, but catalase, superoxide dismutase and mannitol showed no inhibitory effect. CN- ion (100 mM) inhibited the reaction, but N3- ion (100 mM) did not.

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