Transferases conjugation

The reactions are catalyzed by acyl-CoA amino acid A-acyltransferase, of which two distinct A-acyltransferases exist in mammalian mitochondria. The predominant transferase conjugates medium-chained fatty acyl CoA and substituted benzoic acid derivatives with glycine and is termed an aralkyl-CoA glycine A-acyltransferase, while the other enzyme conjugates arylacetic acid derivatives with glycine, glutamine, or arginine and is an arylacetyl-CoA amino acid A-transferase. 

Fujioka, K., Casida, J.E. (2007). Glutathione S-transferase conjugation of organophosphorus pesticides yelds S-phospho-, S-aryl-, and S-alkylglutathione derivatives. Chem. Res. Toxicol. 20 1211-17. 

MotoyamaN, Dauterman WC. 1978. Multiple forms of rat liver glutathione S-transferases Specificity for conjugation of 0-alkyl and 0-aryl groups of organophosphorus insecticides. J Agr Food Chem 26 1296-1301. 

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). 

Soffers AEMF, Ploeman JHTM, Moonen MJH, Wobbes T, van Ommen B, Vervoort J, et al. Regioselectivity and quantitative structure-activity relationships for the conjugation of a series of fluoronitrobenzenes by purified glutathione S -transferase enzymes from rat and man. Chem Res Toxicol 1996 9 638-46. 

Oakley AJ, Lo Bello M, Mazzetti AP, Federici G, Parker MW. The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase Pl-1 in two different modes. FEES Lett 1997 419 32-6. 

Once bilirubin enters the hepatocytes, it can bind to certain cytosolic proteins, which help to keep it solubilized prior to conjugation. Ligandin (a family of glutathione S-transferases) and protein Y are the involved proteins. They may also help to prevent efflux of bilirubin back into the blood stream. 

Figure 32-14. Conjugation of bilirubin with glucuronic acid. The glucuronate donor, UDP-glucuronic acid, is formed from UDP-glucose as depicted. The UDP-glucuronosyl-transferase is also called bilirubin-UGT.

Figure 32-15. Diagrammatic representation of the three major processes (uptake, conjugation, and secretion) involved in the transfer of bilirubin from blood to bile. Certain proteins of hepatocytes, such as ligandin (a family of glutathione S-transferase) and Y protein, bind intracellular bilirubin and may prevent its efflux into the blood stream. The process affected in a number of conditions causing jaundice is also shown.

Dekant W, Martens G, Vamvakas S, et al. 1987. Bioactivation of tetrachloroethylene. Role of glutathione S-transferase-catalyzed conjugation versus cytochrome P-450-dependent phospholipid alkylation. Drug Metab Dispos Biol Fate Chem 15 702-709. 

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. 

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