Uridine diphosphoglucuronic acid

Glucuronides were produced continuously in an enzyme membrane reactor from aglycones and /3-D-uridine diphosphoglucuronic acid (UDPGA) in the presence of a guinea-pig liver preparation of /3-glucuronidase for between 24 and 118 h (Pfaar, 1999). 

Bossuyt X, Blanckaert N. Carrier-mediated transport of uridine diphosphoglucuronic acid across the endoplasmic reticulum membrane is a prerequisite for UDP-glucuronosyltransferase activity in rat liver. Biochem. J. 1997 323 645-648. 

In vitro experiments can sometimes provide valuable insight into what is happening in vivo that is limiting oral bioavailability. The typical experiments, often employed in tandem, to understand bioavailablilty are determinations of compound solubility, membrane permeability, and stability in subcellular fractions. The membrane permeability assays that are most often employed are either a measurement of permeability through an artificial membrane (Parallel artificial membrane permeability assay, PAMPA, is the most common technique) or a cell monolayer (Caco-2, a human colon carcinoma-derived cell line, is the most common cell monolayer). The subcellular fractions most often employed are plasma (for ester-containing compounds) and liver microsomes with the addition of either reduced nicotinamide adenine dinucleotide phosphate (NADPH) or uridine diphosphoglucuronic acid (UDPGA) as cofactor. 

Hjelle, J. J., Hazelton, G. A., and Klaassen, C. D. (1985) Acetaminophen decreases adenosine 3 -phosphate 5 -phosphosulfate and uridine diphosphoglucuronic acid in rat liver. Drug Metab. Dispos. 13, 35 41. 

UDPGA, uridine diphosphoglucuronic acid PAPS, 3 -phospoadenosine-5 -phosphosulfate SAM, S-adenosylmethionine. 

UDPGA B uridine diphosphoglucuronic acid PAPS B 3-phosphoadenosine 5 phosphosulfate GSH > glutathione (g-glutamyl-cysteinyl-glycine)... 

Glucuronidation occurs at oxygen and nitrogen atoms and is one of the most common phase II reactions. It can occur with alcohols, phenols, hydro-xylamines, carboxylic acids, amines, sulfonamides, and thiols and utilizes the energy-rich co-factor uridine diphosphoglucuronic acid (UDPGA). 

MDR-ABC Transporters. Figure 3 Detoxification cellular mechanisms. X, toxic compound X-OH, oxidized toxic compound GS-X, conjugated toxic compound OATP, organic anion transporting proteins CYPs, cytochromes GSH, glutathion UDPGIcUA, Uridine 5-diphosphoglucuronic acid PAPs, 3-phosphoadenylylsulfate. 

Capiello, M., Guiliani, L., Pacifici, G. M., Distribution of UDP-glucuronosyl transferase and its endogenous substrate uridine 5-diphosphoglucuronic acid in human tissues, Pur. J. Clin. Pharmacol. 1991, 41, 345-350. 

Such a transition state might be significantly stabilized by the neighboring carbonyl function, and it would explain the requirement for an a-keto acid intermediate in the uridine diphosphoglucuronate decarboxylase reaction. 

Gygax D, Spies P, Winkler T, Pfaar U. Enzymic synthesis of p-D-glucuro-nides with in situ regeneration of uridine 5 -diphosphoglucuronic acid. Tetrahedron 1991 47 5119-5122. 

S-T etrahydro-5 -oxo-2-furancarboxy 1 Toluenesulphonyl chloride Uridine-5 -diphosphoglucuronic acid Ultraviolet... 

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