Glucuronidation reactions processes

Biotransformation reactions can be classified as phase 1 and phase 11. In phase 1 reactions, dmgs are converted to product by processes of functionalization, including oxidation, reduction, dealkylation, and hydrolysis. Phase 11 or synthetic reactions involve coupling the dmg or its polar metaboHte to endogenous substrates and include methylation, acetylation, and glucuronidation (Table 1). 

N- Glucuronides have been isolated as urinary or biliary metabolites of many aromatic and aliphatic amines, the reaction being of minor quantitative importance in comparison to N- acetylation and other C- or A/-oxidative processes (see (B-80MI10909)). The only reported example of glucuronidation at a tertiary alicyclic nitrogen appears to be in... 

Certain jS-glucuronides are electrophilic in nature and may also function in toxication processes. Covalent binding of the aglycone portions of several carboxylic acid (ester) glucuronides is known to occur to nucleophilic sites on serum albumin via transacylation reactions, for example. 

The liver is the principal organ responsible for xenobiotic metabolism. One of its major roles is to convert lipophilic nonpolar molecules to more polar water-soluble forms. The drug molecule (a xenobiotic) can be modified by phase I reactions, which alter chemical structure by oxidation, reduction, or hydrolysis or by phase II reactions, which conjugate the drug (glucuronidation or sulfation) to create more water-soluble forms. Typically, both phase I and phase II reactions occur. Most drug metaboHsm takes place in the microsomal fraction of the hepatocytes, where many environmental chemicals and endogenous biochemicals (xeno-biotics) are also processed by the same mechanisms. 

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