2.4.2 Cofactors

2.4.2 Cofactors

1. Some enzymes need help

   • Some enzymes (particularly the ones involved in catalysing oxidation-reduction reactions) only work if another small non-protein molecule is attached to them
     • These small molecules are cofactors. Cofactors are a substance that has to be present to ensure than an enzyme-catalysed reaction takes place at the appropriate rate

2. Prosthetic groups

   • A cofactor permanently bound to an enzyme molecule by covalent bonds are prosthetic groups, they are part of the enzyme structure
   • The enzyme carbonic anhydrase contains a zinc ion permanently bound, as a prosthetic group, to its active site
     • Carbonic anhydrase is found in erythrocytes and catalyses the conversion of CO2 and H2O to carbonic acid which then breaks down to protons and HCO3- ions
       • The reaction may proceed in either direction depending on the conc. of substrate or product molecules
       • This reaction is very important as it enables CO2 to be carried in the blood from respiring tissues to the lungs
     • Zinc is important for humans as well as being needed to make carbonic anhydrase. It is necessary for insulin to function correctly so people whose diets don't contain much meat may be zinc efficient. However, some genetically modified crops, like plantain, are nutritionally enhanced to contain more zinc. It is useful as meat is still too expensive for many people in Africa but plantain is their staple diet

3. Other cofactors

   • Some enzymes work better in the presence of ions that are NOT permanently bound to them, they are also cofactors
   • During an enzyme-catalysed reaction, the enzyme and substrate molecules temporarily bind together to form an enzyme-substrate complex
   • The presence of certain ions that can temporarily bind to either the substrate or enzyme may ease the formation of enzyme-substrate complexes and therefore increate the rate of reaction
   • Some cofactors act as co-substrates - they and the substrate form the correct shape to bind to the enzymes active site
   • Some cofactors change the charge distribution on the surface of the substrate or the enzymes active site and make temp bonds in the enzyme-substrate complex easier to form
   • The enzyme amylase digests starch to maltose and only functions if Cl- ions are present

4. Learning tip:

   • Coenzymes are a type of cofactor. They are organic but not made of protein. They bind temporarily to the enzymes active site
   • Metallic ions may also be cofactors of certain enzymes. Some stay bound to the enzyme permanently, forming prosthetic groups
   • Some metallic ions temp bind to the enzyme or substrate to aid the formation of the enzyme-substrate complex
   • Some non-metallic ions are cofactors

5. Coenzymes

   • Coenzymes are small organic non-protein molecules that temp bind to the enzymes active site before or at the same time the substrate binds
   • Coenzymes are chemically changed during the reaction and need to be recycled to their original state, often by another enzyme

6. Some vitamins are sources of coenzymes

   • Many coenzymes are derived from water-soluble vitamins, if the vitamins are deficient then certain diseases may result
     • Vitamin B12, derived from cobalamin coenzymes, leads to pernicious anaemia (progressive fatal anaemia)
     • Folic acid, derives from tetrahydrofolate, leads to megablastic anaemia (large, irregular shaped erythrocytes)
     • Vitamin B3 (nicotinamide), derives from NAD and NADP, leads to pellagra (diarrhoea, dementia and dermatitis)
       • NAD and NADP are hydrogen acceptors, both derivatives of nucleic acids
     • Vitamin B6 (Pantothenate), derives from coenzyme A, leads to elevated bold-plasma triglyceride levels
     • Vitamin B1 (Thiamine), derives from thiamine pyrophosphate, leads to beriberi (mental confusion, irregular heartbeat, muscle weakness, paralysis and heart failure)