Some science behind the scenes

Purine synthesis inhibitors

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.  Purine synthesis inhibitors are antimetabolites that inhibit the proliferation of cells, especially leukocytes. They are thus a class of immunosuppressants.  These inhibitors are used in organ transplantation but they are also used for so called 'autoimmune diseases' such as rheumatoid arthritis or inflammatory bowel disease such as Crohn's disease and ulcerative colitis.

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism.   Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid. Main representatives of these drugs are:

  • purine analogues  - purine synthesis inhibitors that inhibit the synthesis of purine
  • pyrimidine analogues  - pyramidine synthesis inhibitors that inhibit the synthesis of pyramidine
  • antifolates 

Anti-metabolites thus masquerade as a purine (azathioprine, mercaptopurine) or a pyrimidine, or folic acid chemicals that become the building-blocks of DNA. They prevent these substances becoming incorporated in to DNA during the S phase (of the cell cycle), stopping normal development and division. 

As you can see, the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are sometimes used as chemotherapy for cancer.

So how, you might ask, can this class of drugs help in suppressing the immune system.  Well many of those cells are used in the immune system response – they are leukocytes for example and T cells.  Thus these drugs inhibit the production of our immune system cells – there are not as many attacking cells produced, which is why they are believed to help in combatting the autoimmune diseases because they reduce the number of cells doing the attacking.  But then of course this depends on whether you believe that autimmune diseases actually exist.  Purine synthesis inhibitors for example, inhibit the proliferation of cells, but especially leukocytes. 


For iPad/iPhone users: tap letter twice to get list of items.