The role of the liver in the metabolism of carbohydrates

From the total amount of glucose entering from the intestine the liver extracts its most part and uses: 10-15% of that quantity for the synthesis of glycogen, 60% for the oxidative breakdown, and 30% for the synthesis of fatty acids.

The liver maintains blood glucose concentrations at a level that ensures the continuous supply of glucose to all tissues. This is achieved by regulation of the relationship between synthesis and breakdown of glycogen, deposited by the liver. At the average human liver contains up to 100 grams of glycogen. In the absorption of glucose from the intestine contents of a portal vein blood may rise to 18-20 mmol / l, in the peripheral blood in half. Glucose is converted in the liver to glycogen and is deposited, and is used for energy supply. If, after these transformations, there is still excess glucose, it is converted into fat. The liver during starvation maintains constant blood sugar levels, especially by the splitting of glycogen, and if it is not enough – by gluconeogenesis. Insulin, passing through the liver, also has an effect on blood sugar level and the formation and breakdown of glycogen in the liver.

Glucose-6-phosphate plays a central role in the conversion of carbohydrates and self-regulation of carbohydrate metabolism. In the liver glucose-6-phosphate significantly slows phosphorolytic breakdown of glycogen, it activates an enzymatic transport of glucose from uridinediphosphate glucose to the molecule of being built glycogen; it is a substrate for oxidative conversion of the pentose phosphate pathway. During the oxidation of glucose-6-phosphate reduced form of NADP is formed. It is necessary coenzyme for reductive synthesis of fatty acids and cholesterol, and conversion of the glucose-6-phosphate into pentose phosphates - essential components of nucleotides and nucleic acids. In addition, glucose-6-phosphate is a substrate for further glycolytic conversions, leading to the formation of pyruvic and lactic acids. This process provides the body with compounds necessary for the biosynthesis and plays an important role in the energy metabolism. Finally, the splitting of glucose 6-phosphate provides entry of free glucose into the blood delivered by the bloodstream to all organs and tissues.

Gluconeogenesis actively takes place in the liver. Precursors of glucose in gluconeogenesis are pyruvate, alanine (coming from the muscles), glycerol (from adipose tissue) and a number of glycogenic amino acids (coming from food).

High concentrations of ATP and citrate inhibit glycolysis through allosteric regulation of the enzyme phosphofructokinase. ATP inhibits pyruvate kinase. Inhibitor of pyruvate kinase is acetyl-CoA. All these metabolites are formed during the decay of glucose (feedback inhibition). AMP activates the breakdown of glycogen and inhibits gluconeogenesis.

Fructose-2,6-bisphosphate plays an important role in the liver metabolism. It is produced in very small amounts from fructose-6-phosphate and serves a regulatory function: it stimulates glycolysis by activating phosphofructokinase and inhibits gluconeogenesis by inhibition of fructose-1,6-biphosphatase.

In many pathological conditions, including diabetes, there is a change in the operation and regulation of fructose-2,6-bisphosphate. In experimental diabetes in rats the content of fructose-2,6-diphosphate in hepatocytes is reduced. Consequently, the rate of glycolysis is decreased and the rate of gluconeogenesis is increased. Increasing of glucagon concentration and reducing of insulin content are responsible for an increased concentration of cAMP in liver tissue and increased cAMP-dependent phosphorylation of the bifunctional enzyme, which leads to the decrease of its kinase activity and increase of its biphosphatase activity.