Enzymes

• General principle is that they increase the rate of reactions by causing optimal conditions to occur (i.e. are catalysts; biological catalysts per se)
• Main features of enzymes are: catalysis, specificity (complex three-dimensional structure resulting in highly specific binding site), regulation (the rate of a biochemical pathway is often controlled by regulating the activity of enzymes along the path)

Le Chatelier’s principle

If a chemical equilibrium experiences a change in concentration or partial pressure, the equilibrium shifts to counteract this change and a new equilibrium is reached

• Types of Enzymes
  • Oxidoreductases, which catalyse oxidation and reduction (redox) reactions
  • Transferases, which transfer functional groups (e.g. a kinase transfers a phosphate group) from one molecule to another
  • Hydrolases, which catalyse hydrolysis reactions
  • Lyases, which cleave bonds by means other than hydrolysis and oxidation
  • Isomerases, which allow a molecule to interconvert between its isomers
  • Ligases, which use energy (derived from ATP hydrolysis) to join two molecules together with covalent bonds
• Cofactor: non-protein molecules that are required by enzymes (e.g. cytochrome P450 group of enzymes all contain $\mathrm{Fe}{}^{2+}$)
• Coenzyme: organic molecules required by enzymes (e.g. Coenzyme A is used by acetyl-CoA carboxylase to transfer acyl groups)

Clinical Relevance

• Cytochrome P450 metabolises most anaesthetic drugs (notable exceptions being atracurium and cistracurium, catecholamines, suxamethonium, mivacurium and remifentanyl)
• Monoamine oxidase metabolises monoamine catecholamines (e.g. adrenaline, dopamine, noradrenaline)
  • Indirect-acting sympathomimetics may precipitate a potentially fatal hypertensive crisis when patients are taking MAO inhibitors. Where necessary, direct acting sympathomimetics (e.g. isoprenaline) can be used at a reduced dose, as they are also metabolised by another enzyme, catechol-O-methyl transferase (COMT)
• Pseudocholinesterase (plasma cholinesterase or butyrylcholinesterase) metabolises suxamethonium and mivacurium
  • Patients who lack this enzyme can develop suxamethonium apnoea
• Acetylcholinesterases hydrolyse the neutotransmitted acetylcholine terminating neurotransmission
  • Neostigmine is a reversible AChE inhibitor which increases concentration of ACh in the synaptic cleft and competitively displaces non-depolarising muscle relaxants from their receptors
• Non specific tissue and plasma esterases rapidly hydrolyse ramifentanyl and esmolol (hence why esmolol is able to be used as an infusion)

Sources

• Chambers, D., Huang, C., Matthews, G., 2019. Basic Physiology for Anaesthetists, 2nd ed. Cambridge University Press. https://doi.org/10.1017/9781108565011