Carbohydrate metabolism


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The metabolism of the sugars found in our food is discussed in all textbooks and I will not take up all of the details here. The points I do wish to discuss are concerned with maintenance of blood sugar levels under differing physiological conditions. How do we start up storage of glucose after a meal? How do we preserve blood glucose levels between meals? What are the differences in metabolism of common sugars in various organs?

Transport of Glucose in and out of the Liver
The whole thing begins with transport of sugars over tissue membranes. These "small" sugars (glucose, fructose and galactose) are so large that they cannot cross cell membranes without "carriers". Sugar carriers are proteins embedded in the cell's outer membrane that provide transport systems for monosaccharides. The glucose transport protein family (called GLUT) is discussed elsewhere in MedBio. Click here for more information. The point to note now is that these carriers are bidirectional; they can transport glucose both into and out of cells. The direction of movement is determined by the concentrations of glucose in and outside of the liver cell. This is illustrated in the figure to the left.

Drawing "1" shows the situation when the portal blood and the liver cell have equal concentrations of glucose; sugar moves in both directions simultaneously. This may seem to be wasteful, but gears the system to react to small changes in glucose concentration.

The second drawing shows what happens when blood glucose tends to fall. Glucose production in the liver accelerates and the net flow of glucose is outward, stabilizing the blood sugar level. This is extremely important. The total amount of sugar present in the blood can support resting activity for about 40 minutes. Just walking increases glucose use to a point where the entire blood content is used up in about 15 minutes. Since mental activity is completely dependent upon stable blood glucose levels, there must be a way of evening out blood glucose levels. This is one of the major duties of the liver. On a short-term basis, this is the only organ capable of replacing blood sugar used by other organs. Click here for the details.

Following a meal, the portal blood sugar level increases. This is shown in the third drawing where we see that the liver rapidly takes up glucose from the blood. Once again, the liver stabilizes blood sugar. In principle, this two-way flow of glucose can forego in most tissues. However, only the liver and kidneys are sugar producers and export of glucose occurs only in these tissues. Most of our organs are sugar-burners, taking up glucose from the blood and using it for energy production.

What determines this limit on release of glucose from most of the body? Why cannot skeletal muscles release glucose from their large glycogen stores? The secret is that uptake of sugars to our organs involves immediate phosphorylation at either carbon 1 or 6. The phosphorylated sugar derivatives cannot "leak" out of the cell. There is no mechanism for their cross-membrane transport. Once sugars are phosphorylated they stay put!

What is the key to production of glucose in the liver and kidneys? These organs produce a specific enzyme, glucose-6-phosphatase, that cleaves the glucose-phosphate bond. Regulation of the balance between phosphorylating and dephosphorylating enzymes is crucial and determines the net direction of uptake and release of glucose in these organs.

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