Catechol biotransformation reactions

In the liver two phases of biotransformation reactions can take place phase I transformations that introduce polar groups (hydroxyls) in the molecule, and phase II reactions which include conjugations with glucuronic acid, sulphate, or glycine to yield water-soluble metabolites which are excreted in urine. 0-Methylations, to inactivate catechol moieties in these molecules, are also phase II reactions. Phase I reactions are not important in natural phenolic metabolites since they generally contain several polar hydroxyl groups). Phase II reactions increase the molecular weight of the phenolics and promote their secretion into bile. 

In some cases enzymes can increase the rate of reaction by up to lO times. Carnell and Roberts (1997) have briefly discussed the scope of biotransformations that are used to make pharmaceuticals like penicillins, cephalosporines, erythromycin, lovastatin, cyclosporin, etc., and for food additives like citric acid, L-glutamate, and L-lysine. A very successful transformation by Zeneca has been that of benzene reduction, with Pseudomonase Putida, to dihydrocatechol and catechol the dihydro derivative is used to produce (+/-) pinitol. Fluorobenzene has been converted to fluorodihydrocatechol, an intermediate for pharmaceuticals. The highly stereo selective Bayer-Villeger reaction has been carried out with genetically engineered S-cerevisvae. Hydrolases have allowed enantioselective, and in some cases regioselective, hydrolysis of racemic esters. 

The methyl transferases (MTs) catalyze the methyl conjugation of a number of small molecules, such as drugs, hormones, and neurotransmitters, but they are also responsible for the methylation of such macromolecules as proteins, RNA, and DNA. A representative reaction of this type is shown in Figure 4.1. Most of the MTs use S-adenosyl-L-methionine (SAM) as the methyl donor, and this compound is now being used as a dietary supplement for the treatment of various conditions. Methylations typically occur at oxygen, nitrogen, or sulfur atoms on a molecule. For example, catechol-O-methyltransferase (COMT) is responsible for the biotransformation of catecholamine neurotransmitters such as dopamine and norepinephrine. A-methylation is a well established pathway for the metabolism of neurotransmitters, such as conversion of norepinephrine to epinephrine and methylation of nicotinamide and histamine. Possibly the most clinically relevant example of MT activity involves 5-methylation by the enzyme thiopurine me thy Itransf erase (TPMT). Patients who are low or lacking in TPMT (i.e., are polymorphic) are at... 

Further details of the pathways for the degradation of PAFIs are described in Chapter 6, Section 6.2.1 and in a review (Neilson and Allard 1998). It seems that most of the degradative enzymes are inducible, and this is consistent with the fact that most strains have been isolated after specific enrichment with the xenobiotic. The case of the partially constitutive synthesis of catechol 1,2-dioxygenase in the yeast Trichosporon cutaneum (Shoda and Udaka 1980) has been noted (Section 4.5.2). In the case of biotransformation, however, there are sporadic examples of the constitutive synthesis of enzymes. For example, the system carrying out the O-methylation of halogenated phenolic compounds was apparently constitutive (Neilson et al. 1988) this observation is consistent with the isolation of the strains by enrichment with Q compounds structurally unrelated to the halogenated substrates. The O-methylation reaction may function primarily as a detoxification system, so that in this case constitutive synthesis of the enzyme would clearly be advantageous to the survival of the cells. 

It is now well-established that some enzyme families, including various peroxidases and laccases, catalyze the polymerization of vinyl monomers and other redox active species such as phenol-type structures. Vinyl polymerization by these redox catalysts has recently been reviewed 93). These catalysts have been used to prepare polyanilines 94) and polyphenols 95,96). A few examples of related research are included in this book. For example. Smith et al (57) described a novel reaction catalyzed by horseradish peroxidase (HRP). In the presence of HRP and oxygen, D-glucuronic acid was polymerized to a high molecular weight (60,000) polyether. However, the authors have not yet illucidated the polyether structure. Two other oxidative biotransformations were discussed above i) the sono-enzymatic polymerization of catechol via laccase 31), and ii) the oxidation of aryl silanes via aromatic dioxygenases 30). 

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