|
2. Glycan that controls digestion |
|
By having separate research objectives on two different kinds of enzymes, we accidentally found sugar bindings in them respectively which are different from activation of substrate bindings of original enzymes, and then we started our research with the unexpected fact that there are some common points in these sugar bindings. These results indicate that there are characters which recognize information of glycan latent in most of the natural protein molecules, and these characters have not been explained, that is many functions of glycan are still left unsettled. ● Pancreas α-amylase binds with glycoprotein N-binding glycan α-amylase is end typed starch breakdown enzyme that randomly cuts off glucose array ranged by α-1,4 binding and plays the leading role in the process where lots of living systems such as animals and plants and microbes are get energy. Activation of α-amylase in pancreatic juice is one of the enzymes whose interactions with inhibitor and anti-nutrient are well-examined also from the point of view of treatment for diabetes. On the other side, by looking at the function of plant lectin, we took interest in the report that lectin has been grasped as anti-nutrient, especially haricot lectin is classified as a biodefencse molecule because of having array homology with α-amylase, and it actually shows blocking effect on insect raising. Then we searched on interactions between α-amylase in pig pancreas and various plant lectin as well as glycoprotein other than lectin. As a result, we found out that PPA has glycan recognizing ability and bonds with glycoprotein having N-style glycan. In a test tube, enzymatic activation of PPA was not blocked but actually activated due to the interaction with lectin. For 170 years from its discovery in 1830, various extensive researches on PPA have been done, but it is surprising that there is still unknown aspect of PPA 1). 1) Matsushita H., et al. (2002) J. Biol. Chem. 277 , 4680-4686 ● Pancreas trypsin and β-glucuronidase also bind with glycoprotein glycan Glycobinding of α-amylase was limitedly originated in mammal pancreas, and sugar binding with enzymes originated in saliva, plants and microbes was not recognized 2). Then we searched whether there was sugar binding in other pancreatic enzymes and we found there was sugar binding very similar to trypsin, pancreatic protease. Trypsin of pig and cow bonds with N-style glycan of glycoprotein. Detailed sugar specificity has different points from α-amylase. Because trypsin is dried by the interaction with glycan, it activates other zymogen in intestinal duct. This glycan binding is thought to contribute to promote digestion by trypsin’s role as an initiator of digestive function. Recently we found lactose/lactosamineon binding in lysosome enzyme, β-glucuronidase 3). Now, along with these enzymes, we research on glycan bindings that various digestive enzymes have as well as their biological functions.
2)
Takekawa et al.,
J. Biol. Chem.,
281
(13):8528-38 (2006)
|
