Blood glucose levels and the role of the liver

One of the main functions of the liver is to participate in the maintaining of blood glucose levels within well defined range (in the healthy state before meals 60-100 mg/dL or 3.33-5.56 mmol/L). To do it the liver releases glucose into the bloodstream in:

• fasting state;
• between meals;
• during physical activity.

Blood glucose levels and hepatic glucose 6-phosphatase

In the liver, glycogen is the storage form of glucose which is released from the molecule not as such, but in the phosphorylated form i.e. with charge, the glucose 1-phosphate (this process is called glycogenolysis). The phosphorylated molecule can’t freely diffuse from the cell, but in the liver it is present the enzyme glucose-6-phosphatase that hydrolyzes glucose 6-phosphate, produced from glucose 1-phosphate in the reaction catalyzed by phosphoglucomutase, to glucose (an irreversible dephosphorylation).

glycogen_{(n glucose residues)} + P_i → glucose 1-phosphate + glycogen_{(n-1 glucose residues)}

glucose 1-phosphate ↔ glucose 6-phosphate

glucose 6-phosphate + H₂O → glucose + P_i

Then, glucose can diffuse from the hepatocyte, via a transporter into the plasma membrane called GLUT2, into the bloodstream to be delivered to extra-hepatic cells, in primis neurons and red blood cells for which it is the main, and for red blood cells the only energy source (neurons, with the exception of those in some brain areas that can use only glucose as energy source, can derive energy from another source, the ketone bodies, which becomes predominant during periods of prolonged fasting).

Note: the liver obtains most of the energy required from the oxidation of fatty acids, a class of lipids, and not from glucose.
Glucose-6-phosphatase is present also in the kidney and gut but not in the muscle and brain; therefore in these tissues glucose-6-phosphate can’t be released from the cell.
Glucose 6-phosphatase plays an important role also in gluconeogenesis.

Glucose 6-phosphatase is present into the membrane of endoplasmic reticulum and the hydrolysis of glucose-6-phosphate occurs into its lumen (therefore this reaction is separated from the process of glycolysis). The presence of a specific transporter, the glucose 6-phosphate translocase, is required to transport the phosphorylated molecule from citosol into the lumen of endoplasmic reticulum. Although a glucose transporter is present into the membrane of endoplasmic reticulum, most of the released glucose is not transported back into the cytosol of the cell but is secreted into the bloodstream. Finally, an ion transporter transports back into the cytosol the inorganic phosphate released into the endoplasmic reticulum.

References

1. Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 6th Edition. W.H. Freeman and Company, 2012
2. Roach P.J., Depaoli-Roach A.A., Hurley T.D and Tagliabracci V.C. Glycogen and its metabolism: some new developments and old themes. Biochem J 2012;441:763-787. doi:10.1042/BJ20111416
3. Stipanuk M.H., Caudill M.A. Biochemical, physiological, and molecular aspects of human nutrition. 3rd Edition. Elsevier health sciences, 2012