HP is caused by ìSuper-Trypsinî

Whitcomb et al, Nature Genetics 1996

Trypsin

Active trypsin in the pancreaswill cause the pancreas to digestitself.

Normally, the pancreas is protected because active trypsin will destroy itself by cutting at R117. This will split the trypsin and inactivate it.

In HP, R117 is mutated to H117. This creates a ìsuper-trypsinî that cannot be inactivated and leads to acute pancreatitis.

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The trypsin molecule is illustrated in yellow and blue and is shaped like a pac-man with the jaws opening to the left. If a protein chain with an arginine or lysine inters the jaw it is rapidly cut into two peices.

Tryspinogen is made by the pancreas in an inactive form. It is one of the most important enzymes because one it is activated to trypsin in the intestine, it is responsible for activating nearly all of the other digestive enzymes to their active form, in

If trypsinogen becomes active in the pancreas it could activate all of the other digestive enzymes and cause the pancreas to digest itself. Forturnately, the pancreas also makes a trypsin inhibitor (PSTI - in red) that plugs the active site and prevents

Solving the genetic code for hereditary pancreatits proved that the mutation was at R117 changing it to Histidine 117.