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• Oxidative deamination of primary aliphatic amines

  1. Oxidation through the carbinolamine pathway by CYP

  2. Leads to formation of carbonyl metabolites and ammonia

  
• 1. oxidation of primary aliphatic amines

  1. Leads to formation of N-hydroxylamine metabolites

  2. Further oxidation yields N-oxygenated products like nitroso and nitro

  
• Oxidative N-dealkylation and N-oxide formation of tertiary aromatic amines and secondary aromatic amines

  1. Further oxidation of N-hydroxylamine leads to nitrone products

  2. Nitrone products may be hydrolyzed to primary hydroxylamines

  
• 1. oxidation of primary aromatic amines


  1. Generates the N-hydroxylamine metabolite

  2. Oxidation of hydroxylamine to nitroso derivative can occur

  
• Oxidative carbon-nitrogen bond cleavage (via α-carbon hydroxylation) and N-hydroxylation of amides


  1. Oxidative dealkylation proceeds via an initially formed carbinolamide

  2. Carbinolamide is unstable and fragments to form the N-dealkylated product

  
• Hydroxylation of alicyclic carbon to nitrogen atom in cyclic amides or lactams

  Leads to carbinolamides

  
• Oxidation of ethers


  1. Initial α-carbon hydroxylation to form hemiacetal or hemiketal

  2. Spontaneous carbon-oxygen bond cleavage yields dealkylated oxygen species and carbonyl moiety

  
• 1. dealkylation of drugs containing carbon-sulfur functional group

  Oxidative carbon-sulfur bond cleavage

  
• Desulfuration


  Oxidative conversion of carbon-sulfur double bonds (C=S) to carbon-oxygen double bond (C=O)

  
• 1. oxidation


  1. Yields corresponding sulfoxide derivatives

  2. Sulfoxide may further oxidise to sulfones
• Oxidation of alcohols and aldehydes

  1. Alcohol or carbinol metabolites generated as intermediates

  2. Unconjugated alcohols further oxidized to aldehydes or ketones

  3. Aldehyde metabolites often oxidized to carboxylic acids

  
• Alcohol dehydrogenases


  Catalyze bioconversion of alcohols to aldehydes and ketones

  
• Oxidation of secondary alcohols to ketones is not often important as it reduces back to secondary alcohol</b>

  
• Oxidative aromatization reactions


  Example: Progesterone derivative norgestrel

  
• Oxidative dehalogenation reactions


  Example: Volatile anesthetic agent halothane

  
• Reduction of aldehydes

  Reduced to primary alcohols

  
• Reduction of ketones


  1. Reduced to secondary alcohols

  2. Reactions mediated by aldo-keto reductase enzymes

  3. Can produce two stereoisomeric alcohols with potential stereo selectivity

  
• Reduction of aromatic nitro and azo compounds

  1. Initially reduced to nitroso and hydroxylamine intermediates

  2. Further reduced to primary amine metabolites

  3. Azo reduction proceeds via hydrazo intermediate that is cleaved reductively

  
• Hydrolysis of esters and amides

  1. Catalyzed by hydrolytic enzymes

  2. Produces polar metabolites like carboxylic acids, alcohols, phenols, and amines

  
• Esterases


  Enzymes carrying out ester hydrolysis, found in liver, kidney, intestine, and plasma
• Amidases, esterases, and deacylases

  Enzymes mediating amide hydrolysis, found in liver microsomes
• Esters are more easily hydrolyzed than amides
• Ester hydrolysis


  • Conversion of aspirin to salicylic acid
• Amide hydrolysis is relatively slow compared to ester hydrolysis

  
• Hydrolysis of recombinant human peptide drugs and hormones

  1. Carboxypeptidase and aminopeptidase cleave N- or C-terminal amino acids

  2. Examples: insulin, growth hormone, prolactin, parathyroid hormone
• Hydrolysis of other compounds

  Phosphate esters, sulfonylureas, cardiac glycosides, carbamate esters, organophosphates