A D-glucuronic acid in cyclic pyranose form.
ChEBI ID: 47952
There are 2 compounds belonging to this class, involving 3 studies.
| Member | Definition | Role |
|---|---|---|
| beta-D-glucuronic-acid | A D-glucopyranuronic acid in which the anomeric centre has beta-configuration. | metabolite |
| alpha-D-glucuronic-acid | A D-glucopyranuronic acid in which the anomeric centre has alpha-configuration. |
| Pre-1990 | 1990-2000 | 2001-2010 | 2011-2020 | Post-2020 |
|---|---|---|---|---|
| 1 | 1 | 1 | 0 | 0 |
| Article |
|---|
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.
A cDNA encoding a multispecific organic anion transporter 3 (hOAT3) was isolated from a human kidney cDNA library. The hOAT3 cDNA consisted of 2179 base pairs that encoded a 543-amino-acid residue protein with 12 putative transmembrane domains. The deduced amino acid sequence of hOAT3 showed 36 to 51% identity to those of other members of the OAT family. Northern blot analysis revealed that hOAT3 mRNA is expressed in the kidney, brain, and skeletal muscle. When expressed in Xenopus laevis oocytes, hOAT3 mediated the transport of estrone sulfate (K(m) = 3.1 microM), p-aminohippurate (K(m) = 87.2 microM), methotrexate (K(m) = 10.9 microM), and cimetidine (K(m) = 57.4 microM) in a sodium-independent manner. hOAT3 also mediated the transport of dehydroepiandrosterone sulfate, ochratoxin A, PGE(2), estradiol glucuronide, taurocholate, glutarate, cAMP and uric acid. Estrone sulfate did not show any trans-stimulatory effects on either influx or efflux of [(3)H]estrone sulfate via hOAT3. hOAT3 interacted with chemically heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, penicillin G, bile salts and tetraethyl ammonium bromide. The hOAT3 protein was shown to be localized in the basolateral membrane of renal proximal tubules and the hOAT3 gene was determined to be located on the human chromosome 11q12-q13.3 by fluorescent in situ hybridization analysis. These results suggest an important role of hOAT3 in the excretion/detoxification of endogenous and exogenous organic anions in the kidney. |
Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
The time course of the tissue accumulation of 16 neutral, cationic, and anionic drugs by resting and 2-Hz stimulated atria of the guinea pig was measured. The accumulation of the substances was quantified by means of their tissue to medium ratios (T/M). Auricles driven with 2 Hz accumulated the drugs faster and during a long period of time to a greater extent than resting atria. By extrapolation of the binding characteristics, the final equilibrium T/M values were estimated. The variance in these accumulation data at equilibrium (log T/M) Could be best described by a linear combination of log P (octanol/water) and the ability of the drugs to bind to atrial homogenate (log percent bound/percent free). A parameter calculated from protein binding appeared less significant. Comparable results were obtained for the accumulation data measured in resting and 2-Hz stimulated atrial muscles. It is suggested that the degree of accumulation of drugs into atrial tissue is determined by the facility of their penetration of the plasma membrane and the extent of their intracellular binding. |
Morphine 6-glucuronide and morphine 3-glucuronide as molecular chameleons with unexpected lipophilicity.
Morphine 6-glucuronide, but not morphine 3-glucuronide, is a highly potent opiate receptor agonist. In fact, there is converging evidence that much of the analgesic effect occurring after morphine treatment in humans is due to this metabolite rather than to the parent drug. Yet glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier and rapidly excreted by the urinary and/or biliary routes. Here, we report that morphine 6-glucuronide, and to a lesser extent morphine 3-glucuronide, are far more lipophilic than predicted, and in fact not much less lipophilic than morphine itself. Force-field and quantum mechanical calculations indicate that the two glucuronides can exist in conformational equilibrium between extended and folded forms. The extended conformers, because they efficiently expose their polar groups, must be highly hydrophilic forms predominating in polar media such as water; in contrast, the folded conformers mask part of their polar groups, thus being more lipophilic and likely to predominate in media of low polarity such as biological membranes. |