Alpha-Glucosidase Inhibitors

Alpha-Glucosidase Inhibitors work to control diabetes by inhibitign the enzymes that break down starches and carbohydrates in the body, lowering the necessity for insulin. This is accomplished through competitive, reversible inhibition of pancreatic alpha amylase and membrane bound intestinal alpha glucoside hydrolase enzymes. The drug is metabolized by the digestive enzymes in the intestine and also by the intestinal bacteria. The pancreatic alpha-amylase breaks down starches (the food storage units in plants) to smaller sugar units, oligosaccharides within the small intestine. The membrane bound intestinal alpha glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monomer sugars in the small intestine. The result of inhibiting these enzymes is delayed and lowered glucose absorption. The inhibitory activity also works against lactase, but has not been shown to induce lactose intolerance, the inability to break down the lactose molecule. The mechanism that is inhibited by this drug is shown below.
 
 

Medication 
Brand Name
Acarbose
Precose
Miglitol
Glyset

Acarbose

This is the strcuture of the alpha-glucosidase acarbose, brand name precose. This drug inhibits enzymes that break down food to produce the sugars that alter the blood sugar level. Images of these enzymes are shown below.

Migitol


This is the structure of Migitol, another inhibitor of the enzymes that break down complex sugar molecules.
 

complex of acarbose with glucoamylase

This is the structure of Glucoamylase, a hydrolase enzyme that breaks down more complex sugars to prodcue the simplier units that the body can use. It is the production of these smaller units that raises the blood sugar, and increases the need for insulin. By inhibiting this enzyme, less insulin is needed and the disorder diabetes does not have such a great effect.

Human Pancreatic -Amylase In Complex With The Carbohydrate Inhibitor Acarbose

This is the structure of the human pancreatic amylas and the inhibitor acarbose.

glycoside hydrolases mechanism

The enzyme gycoside hydrolase breaks down large sugar complexes into smaller units. This is acheived by two catalytic carboxylates in the catalytic domain of the enzyme and the water molecule used to cleave the sugars. The product is one sugar unit removed from the complex.








 Home