Reduction of Glucose
Glucose to SorbitolWe already seen that NADPH reduces a carbonyl group in the formation of a sugar by adding H- to the electrophilic carbonyl carbon.
The enzyme aldehyde reductase catalyzes a similar reaction between NADPH and glucose.
Aldehyde reductase is a barrel-shaped protein consisting of 315 amino acids linked together in a chain. In the center of the barrel is a binding site for NADPH and another for glucose. An acidic hydrogen from the side-chain of one of the tyrosine amino acids is positioned close to the aldehyde carbonyl oxygen.
During the reaction:
A catalyst, such as this enzyme, can only increase the rate of a reaction. It doesn't change the thermodynamics. The reaction between NADPH and glucose is thermodynamically favorable (G is a negative number) but very slow. What would be the rate expression for the uncatalyzed reaction?
The slow step of the reaction catalyzed by aldehyde reductase is the release of NADP+ from the enzyme binding pocket. What is the rate expression for the catalyzed reaction?
Role of Glucose Reduction in DiabetesThe enzyme catalyzed reduction of glucose by NADPH is a minor reaction in the human body when blood glucose levels are in the normal range. However, in uncontrolled diabetics, the blood glucose level is much higher.
The molecule insulin regulates the amount of glucose that enters most cells in the body with the exception of cells in the eye and nerve cells. For these cells, the amount of glucose in the cell depends only on the concentration in the blood.
Once in the cells, glucose can be metabolized in the normal way or it can be reduced as shown above. Diabetics with chronic high blood sugar can have up to 1/3 of their glucose reduced through the pathway involving the aldehyde reduction reaction. This uses up significant amounts of NADPH and leads to significant decreases in the synthesis of other important molecules in these cells. The result is damage to the cells.
Sorbitol, Xylitol and other Sugar AlcoholsThe aldehyde reduction product of glucose is the molecule sorbitol. The reduction of the five carbon sugar xylose produces another sugar alcohol, xylitol.
Sugar alcohols are not metabolized as efficiently as sugars. They have a sweet taste but a lower energy content than table sugar so they are used in some diet foods.
Because bacteria don't break them down readily, sugar alcohols don't cause tooth decay as sugars do. Because of this, they are used as sweeteners in chewing gum and toothpaste.