Isoenzymes and Common

Cytochrome P-450 Isoenzymes and Common Drugs They Metabolize, Inhibit, and Induce0 

Inhibitors Inducers theophylline, propranolol Most fluoroquinolone antibiotics, fluvoxamine, cimetidine Tobacco smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole 

Substrates Inhibitors Inducers CYP2C9 Most NSAIDs (including COX-2), warfarin, phenytoin Fluconazole Barbiturates, rifampin 

Substrates CYP2C19 Diazepam, lansoprazole, omeprazole, phenytoin, 

Inhibitors Inducers pantoprazole Omeprazole, isoniazid, ketoconazole Barbiturates, rifampin 

Substrates CYP2D6 Most lockers, codeine, clomipramine, clozapine. 

Inhibitors Most fluoroquinolone antibiotics, fluvoxamine, cimetldlne 

Inducers Tobacco smoking, charcoal-broiled foods, cruciferous 

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Genetic polymorphisms in CYP450 isoenzymes are common. Among whites, 5-10% of the population carries a mutation of CYP450 2D6, causing them to be slow metabolizers of debriso-quine, mephenytoin, quinidine, metoprolol and dextromethorphan standard doses are more likely to be associated with adverse events as a consequence, especially when a second substrate drag is interacting. 

Antithyroid drags have several side effects. The most frequent side effects are maculopapular rashes, pruritus, urticaria, fever, arthralgia and swelling of the joints. They occur in 1-5% of patients [1, 2]. Loss of scalp hair, gastrointestinal problems, elevations of bone isoenzyme of alkaline phosphatase and abnormalities of taste and smell are less common. The incidence of all these untoward reactions is similar with MMI and PTU. Side effects of MMI are dose-related, whereas those of PTU are less clearly related to dose [1]. PTU may cause slight transient increases of serum aminotransferase and y-glutamyl transpeptidase concentrations but also severe hq atotoxicity whereas methimazole or carbimazole can be associated with cholestasis. The side... 

Another common liver disease, alcoholic liver damage produced by moderate to heavy alcoholic intake, is also reflected by an elevation of the serum GOT and GPT activities. The serim glutamyl transferase activity is reported to be a sensitive index of alcoholic intake and can serve to monitor persons on alcoholic withdrawal programs (60). The LD-5 isoenzyme arises mainly from liver tissue, but has a short half-life (61), which is about 1/5 and 1/2 of the half life of the transaminases, GPT and GOT respectively. Some authors consider that a normal LD-5 isoenzyme activity in a jaundiced patient is sufficient evidence to exclude primary liver disease and that obstruction is probably responsible for the jaundice (62). In hemolytic jaundice the LDH-1 and 2 isoenzymes are elevated. 

Alkaline phosphatases [AP, orthophosphoric-monoester phosphorylase (alkaline optimum) EC 3.1.3.1] represent a large family of almost ubiquitous isoenzymes found in organisms from bacteria to animals. In mammals, there are two forms of AP, one form present in a variety of tissues and another form found only in the intestines. They share common attributes in that the phosphatase activity is optimal at pH 8-10, is activated by the presence of divalent cations, and is inhibited by cysteine, cyanides, arsenate, various metal chelators, and phosphate ions. Most conjugates created with AP utilize the form isolated from calf intestine. 

Hydrogenase isoenzymes are also common among the metabolically more versatile bacteria (see Chapter 2). For instance, H2 metabolism and isoenzyme composition in enteric bacteria, including Escherichia coli and Salmonella typhimurium, appear to be differentially regulated under the two modes of anaerobic life, fermentation and anaerobic respiration (Table 3.1). Furthermore, biosynthesis of the individual isoenzymes appears to be controlled at a global level by the quality of the carbon source. 

Hamberger B, Hahlbrock K (2004) The 4-coumarate CoA ligase gene family in Arabidopsis thaliana comprises one rare, sinapate-activating and three commonly occurring isoenzymes. Proc Natl Acad Sci USA 101(7) 2209-2214... 

Sequence Identity (%) Among Isoenzymes Commonly Used as Template Structures for Homology Modeling and Major Human CYPs Calculated by Clustal W (43)... 

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