Glucuronylation

Pargyline hydrochloride (Eutonyl, (V-methyl-n-propargylbenzylamine hydrochloride) [306-07-0] M 195.7, m 154-155 , 155 , pK 6.9. Recrystd from EtOH-Et20 and dried in vacuo. It is very soluble in H2O, in which it is unstable. The free base has b 101-103°/ 1mm. It is a glucuronyl transferase inducer and a monoamine oxidase inhibitor, [von Braun et al. Justus Liebigs Ann Chem 445 205 1928, Yeh and Mitchell Experientia 28 298 1972 Langslrom et al. Science 225 1480 1984.]... 

UDP-Glucuronyl Transferase Ultrarapid Metabolizer Unstable Angina Unwanted Effects UPR... 

VDP-Glucuronyl transferases (henceforward simply glucuronyl transferases) exist in a number of different forms with contrasting, yet overlapping, substrate... 

The microsomal fraction consists mainly of vesicles (microsomes) derived from the endoplasmic reticulum (smooth and rough). It contains cytochrome P450 and NADPH/cytochrome P450 reductase (collectively the microsomal monooxygenase system), carboxylesterases, A-esterases, epoxide hydrolases, glucuronyl transferases, and other enzymes that metabolize xenobiotics. The 105,000 g supernatant contains soluble enzymes such as glutathione-5-trans-ferases, sulfotransferases, and certain esterases. The 11,000 g supernatant contains all of the types of enzyme listed earlier. 

Apart from monooxygenases, other enzymes concerned wih xenobiotic metabolism may also be induced. Some examples are given in Table 2.5. Induction of glucuronyl transferases is a common response and is associated with phenobarbital-type induction of CYP family 2. Glutathione transferase induction is also associated with this. A variety of compounds, including epoxides such as stilbene oxide and... 

Emphasis is given to the critical role of metabolism, both detoxication and activation, in determining toxicity. The principal enzymes involved are described, including monooxygenases, esterases, epoxide hydrolases, glutathione-5 -transferases, and glucuronyl transferases. Attention is given to the influence of enzyme induction and enzyme inhibition on toxicity. 

The functional form of thyroxine (T3) is generated by the deiodination of T4, and PCBs can influence the tissue levels of this form by disturbing metabolism, as well as by reducing the binding of T4. PCBs have been shown to inhibit the sulfation of thyroid hormones and the deiodination of T4 to T3. They can also induce the glucuronyl transferase that conjugates T4 (Brouwer et al. 1998). 

Glucuronyl transferases A group of enzymes that catalyze the formation of conjugates between glucuronide and a xenobiotic (usually a phase I metabolite). 

Morcillo, Y., Janer, G., and O Hara, S.C.M. et al. (2004). Interaction of tributyl tin with cytochrome P450 and UDP glucuronyl transferase systems of fish in vitro smdies. Environmental Toxicology and Chemistry 23, 990-996. 

The glucuronidation of bifirubin is discussed in Chapter 32 the reactions whereby xenobiotics are glu-curonidated are essentially similar. UDP-glucuronic acid is the glucuronyl donor, and a variety of glu-curonosyltransferases, present in both the endoplasmic reticulum and cytosol, are the catalysts. Molecules such as 2-acetylaminofluorene (a carcinogen), aniline, benzoic acid, meprobamate (a tranquilizer), phenol, and... 

Sasaki, N. et al., Amaranthin in feather cockscombs is synthesized via glucuronylation at the cyc/o-DOPA glucoside step in the betacyanin biosynthetic pathway, J. Plant Res., 118, 439, 2005. 

The assessment of clearance is complicated by the numerous mechanisms by which compounds may be cleared from the body. These mechanisms include oxidative metabolism, most commonly by CYP enzymes, but also in some cases by other enzymes including but not limited to monoamine oxidases (MAO), flavin-containing monooxygenases (FMO), and aldehyde oxidase [45, 46], Non-oxidative metabolism such as conjugation or hydrolysis may be effected by enzymes such as glucuronyl transferases (UGT), glutathione transferases (GST), amidases, esterases, or ketone reductases, as well as other enzymes [47, 48], In addition to metabolic pathways, parent compound may be excreted directly via passive or active transport processes, most commonly into the urine or bile. 

Zidovudine (AZT, ZDV) Retrovi r 1 00-mg caps, 300-mg tabs, 1 0 mg/mF intravenous solution, 1 0 mg/mF oral solution 300 mg bid 1 00 mg tid in severe renal impairment or HD None Bone marrow suppression macrocytic anemia or neutropenia gastrointestinal intolerance, headache, insomnia, asthenia Glucuronyl transferase and renal... 

Stevenson, D.E. and Hubl, U. (1999) Optimization of /3-D-glucuronide synthesis using UDP-glucuronyl transferase Enzyme and Microbial Technology 24, 388-396. 

Easterbrook, J., Liu, C., Sakai, Y. and Li, A.P. (2001) Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metabolism and Disposition The Biological Fate of Chemicals, 29, 141-144. 

Primary Arylamines, and N-Methyl Arylamines. Putative ultimate carcinogenic metabolites are designated I-XIII. Ac, acetyl Gl, glucuronyl. 

The syndrome of IgMk paraproteinemia and sensory ataxia is usually encountered in elderly men. Nerve biopsy in these patients shows focal abnormalities in compaction of PNS myelin lamellae, and their IgM paraprotein recognizes epitopes of myelin-associated glycoprotein (MAG) and sulfate-3-glucuronyl paragloboside [24,42]. 

Scheme 7. General glucuronidation reaction catalyzed by UDP-glucuronyl transferases.

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