Glucose → glucose-6-phosphate.

Insulin induces the synthesis of glucokinase and thus accelerates the phosphorylation of glucose.

Fructose-2,6-bisphosphate allosterically activates phosphofructokinase (glycolysis is increased) and inhibits the phosphatase fructose-1,6-bisphosphatase (gluconeogenesis is slowed down).

Fructose-2,6-bisphosphate is formed by phosphorylation of fructose-6-phosphate with the participation of the bifunctional enzyme. It has two domains with different enzymatic activity.

When it is in dephosphorylated form, it has kinase activity which is characteristic of the absorptive period (insulin-glucagon index is high). Glycolysis is increased.

In phosphorylated form it has phosphatase activity (prolonged starvation, insulin / glucagon index is low). The amount of fructose-2,6-bisphosphate is reduced, glycolysis is slowed down and switched on gluconeogenesis.

During digestion insulin activates protein phosphatase, which dephosphorylates pyruvate kinase, and converts it into active state. The conversion of phosphoenolpyruvate to pyruvate (glycolytic reaction) is accelerated during digestion and slowed down into postabsorbtiv period.

The reactions of gluconeogenesis:

Pyruvate → oxaloacetate → phosphoenolpyruvate

can occur at any state of the organism.

During the digestion because of the acceleration of the initial stages of glycolysis the content of fructose-1,6-bisphosphate is increased, leading to activation of pyruvate kinase (glycolysis is increased).

After a meal rich in carbohydrates, insulin-glucagon index is increased, amount of glucokinase phosphofructokinase, pyruvate kinase (glycolytic enzymes) is increased. It stimulates the glycolytic pathway.

Glucose in liver cells is also used to energy supply of hepatocytes. The main consumers of ATP in the hepatocytes are the transmembrane transport of metabolites, synthesis of proteins, glycogen, fat, and gluconeogenesis.

ATP and AMP are allosteric effectors of some glycolytic enzymes: AMP activates phosphofructokinase and inhibits fructose-1,6-bisphosphatase, ATP inhibits pyruvate kinase. Thus, with the expenditure of ATP concentration of AMP is increased, glycolysis and ATP synthesis are activated, and gluconeogenesis is slowed down.

7.11. Violations of carbohydrate metabolism

Violation of hydrolysis and absorption of carbohydrates

Absorption of carbohydrates is violated at failure of amylolytic enzymes of the gastrointestinal tract (pancreatic juice amylase, etc.). In this situation carbohydrates that come from food are not broken down to monosaccharides and are not absorbed. Carbohydrate starvation is developed. Absorption of carbohydrates is violated in inflammation of the intestinal wall, resulting in impaired glucose phosphorylation. This happens in cases of poisoning of toxins that block the enzyme hexokinase.

Glycogenosis

Glycogenosis is a group of inherited diseases caused by deficiency of enzymes involved in synthesis or breakdown of glycogen.

Glycogenosis of 0 type occurs under glycogen synthase deficiency. It is characterized by a sharp decrease of glycogen in the liver, there is a condition until the development of coma (hypoglycemic syndrome). Patients with glycogen synthase deficiency die at an early age.

Lack of enzymes involved in the breakdown of glycogenleads to its accumulation in organs and tissues (Table 1).

Table 1. The diseases associated with metabolic disorders of glycogen.

Name of disease	Causes	Symptoms
Gierke's disease, glycogen storage disease type I	Hereditary defects of synthesis of glucose-6-phosphatase in liver and kidney	Enlargement of liver (hepatomegaly), kidney, increase in the concentration of pyruvate and lactate in blood, acidosis, hypoglycemia, convulsions, growth retardation
Pompe disease, glycogen storage disease type II	Lack of enzyme -1,4-glucosidase	Abnormal accumulation of glycogene in the cells. Muscle weakness. Enlargement of heart, liver, kidney, spleen
Corey's disease, glycogenosis type III	Decreased activity of amilo-(1-6)-glycosidase and (or) glycogen branching enzyme	Residual time-branching dextrin is accumulated. Growth retardation, liver enlargement, muscular weakness, as a result of the accumulation of residual dextrin in muscles
Andersen's disease, glycogenosis type IV	Violation of glycogen branching enzyme activity, resulting in storage of abnormal glycogen	Enlarged liver, jaundice, cirrhosis, hypoglycemia
McArdle's disease, glycogenosis type V	Lack of muscle phosphorylase	Skeletal muscles are increased in volume and become very dense. Muscle weakness, muscle cramps, tachycardia at doing exercises
Hers' disease, glycogenosis type VI	Lack of hepatic enzyme phosphorylase	Enlargement of the liver, growth retardation, hyperlipemia, hyperglycemia