Phase II reaction

Conjugation reactions usually involve metabolite activation by some high-energy intermediate and have been classified into two general types type I, in which an activated conjugating agent combines with the substrate to yield the conjugated product, and type II, in which the substrate is activated and then combines with an amino acid 

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The predicted metabolites are also the starting point for the phase II metabolic prediction, to find where glucuronidation could occur. All the probable metabolites obtained from CYP metabolism reactions are submitted to a possible phase II reaction catalyzed by UGTs, using the UGT structure(s) as a template. The accessibility component is computed in the UGTcavity to prioritize glucuronic acid transfer. The final metabolite structures are then reported in graphical output or saved to a file. 

In addition to the common pathways, glycolysis and the TCA cycle, the liver is involved with the pentose phosphate pathway regulation of blood glucose concentration via glycogen turnover and gluconeogenesis interconversion of monosaccharides lipid syntheses lipoprotein formation ketogenesis bile acid and bile salt formation phase I and phase II reactions for detoxification of waste compounds haem synthesis and degradation synthesis of non-essential amino acids and urea synthesis. 

Urea ((NH2)2CO), a small and highly water soluble molecule, is an end product of amine and ammonia nitrogen metabolism and as such represents an example of biodetoxification (Section 6.4). The process is discussed in this section because it illustrates a genuine de novo biosynthetic pathway rather than detoxification involving chemical modification, via phase I and phase II reactions, of a pre-existing molecule as is the case for haem or steroid hormones. 

The existence of various isoforms of many of the enzymes involved with phase I and phase II reactions has been noted above. Key enzymes are also subject to variation by genetic polymorphisms so there may be considerable difference in the metabolic efficiency between individuals and between different ethnic groups. Such genetic differences account for most the variability we see between individuals capacity to metabolise certain drugs. For example, refer to Section 6.4.3. 

Examples of phase I and phase II reactions for the metabolism of exogenous and endogenous compounds... 

Two examples will be used to illustrate phase I and phase II reactions paracetamol and the catabolism of haem groups. 

Because of its very low water solubility, bilirubin formed outside the liver must be transported through the circulation bound to albumin. This is called unconjugated bilirubin, indicating that it has not yet passed through the phase II reactions in the liver. 

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