Non-microsomal Enzymes

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Chapter: Essential pharmacology : Pharmacokinetics; Metabolism Excretion Of Drugs, Kinetics Of Elimination

These are present in the cytoplasm and mitochondria of hepatic cells as well as in other tissues including plasma. The flavoprotein oxidases, esterases, amidases and conjugases are nonmicrosomal. Reactions catalysed are:


NON-MICROSOMAL ENZYMES

 

These are present in the cytoplasm and mitochondria of hepatic cells as well as in other tissues including plasma. The flavoprotein oxidases, esterases, amidases and conjugases are nonmicrosomal. Reactions catalysed are:

 

Some oxidations and reductions, many hydrolytic reactions and all conjugations except glucuronidation.

 

The nonmicrosomal enzymes are not inducible but many show genetic polymorphism (acetyl transferase, pseudocholinesterase).

 

Both microsomal and nonmicrosomal enzymes are deficient in the newborn, especially premature, making them more susceptible to many drugs, e.g. chloramphenicol, opioids. This deficit is made up in first few months, more quickly in case of oxidation and other phase I reactions than in case of glucuronide and other conjugations taking 3 or more months.

 

The amount and kind of drug metabolizing enzymes is controlled genetically and is also altered by environmental factors. Thus, marked interspecies and interindividual differences are seen, e.g. cats are deficient in glucuronyl transferase while dogs are deficient in acetyl transferase. Upto 6fold difference in the rate of metabolism of a drug among normal human adults may be observed. This is one of the major causes of individual variation in drug response.

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