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Glucose

Introduction

Carbohydrates are compounds consisting of carbon, oxygen and hydrogen, with a hydrogen to oxygen ratio identical to that found in water (H:O = 2:1). Carbohydrates are divided into simple sugars or monosaccharides (e.g., glucose, galactose, fructose) and complex sugars, i.e. oligosaccharides or polysaccharides (e.g., glycogen, starch). Carbohydrates are mostly of vegetable origin, and are the main source of energy for the human body. The body utilizes the energy derived from carbohydrates for cell growth, other metabolic processes, and biosynthesis of new substances.

The metabolism of carbohydrates
The metabolism of carbohydrates has several phases:
1) food intake,
2) food digestion,
3) food absorption,
4) intracellular metabolism, and
5) excretion of metabolic end products.

A man takes a certain amount of carbohydrates daily into the body. The breakdown of polysaccharides (starch, glycogen) begins in the oral cavity, where a-amylase from the salivary glands degrades starch to maltose. In the oral cavity, a small portion of starch is degraded, because the food is retained there only for a short period of time. Starch breakdown continues in the stomach until the food is so acidified by the gastric juice as to inhibit the α-amylase enzyme, thus preventing its further action on the starch. The starch breakdown continues in the duodenum and small intestine under the action of α-amylase from the pancreas, and disaccharide breakdown begins. Saccharose is degraded to glucose and fructose by the action of saccharase, whereas lactose is degraded to glucose and galactose by the action of lactase. Glucose and galactose are absorbed by active transport, and other monosaccharides by diffusion. Thus absorbed monosaccharides are transported by circulation to the liver, where they are included in further metabolic processes. Glucose is able to directly enter the cells of the liver, brain, kidneys and erythrocytes, whereas insulin serves as a mediator for the glucose to enter the muscular and fatty tissue cells. In the liver, galactose and fructose are included in the metabolic pathways of glucose breakdown. The fate of glucose in the body is variable:
1) glucose is in part deposited in the liver and muscle in the form of glycogen. This glycogen serves as the body's carbohydrate reserve;
2) a part of glucose serves for the synthesis of other substances (e.g., glucoproteins, glucolipids);
3) a part of glucose enters the cells, where it is degraded in the tricarbon acid cycle (Krebs cycle) to CO2 and water, whereby energy is released; and
4) the fourth part of glucose is transformed to fat and deposited in adipose tissue.

The concentration of glucose in the blood ranges from 3.8 to 6.1 mmol/L. When the blood concentration of glucose increases, excessive glucose enters the cells and is deposited in the form of glycogen. If the blood concentration of glucose decreases, e.g., due to starvation, the glycogen will be degraded and will reenter the blood in the form of glucose.
The cellular metabolism of glucose includes the following processes:
1) glycolysis
2) gluconeogenesis
3) glycogenolysis
4) glycogenesis
5) pentose-phosphate pathway
6) citric acid cycle

1) Glycolysis is a series of reactions in which the glucose in cellular cytosol is degraded to pyruvate with simultaneous ATP formation. Glucose is first phosphorylated with ATP molecule to form glucose-6-phosphate, a compound playing a central role in the metabolism of glucose. In anaerobic conditions, pyruvate is reduced to lactate by the action of lactate dehydrogenase (LDH) in the presence of NADH. The process takes place in the muscle on hard physical work.
2) In aerobic conditions, glycolysis precedes the citric acid cycle (Krebs cycle) and electron transport chain (respiratory chain), whereby most of the glucose energy is released with the formation of CO2 and water. The glycolysis and citric acid cycle are connected by oxidation decarboxylation of pyruvate, whereby acetyl-CoA is formed. This reaction and citric acid cycle reactions take place in the mitochondria
3) Gluconeogenesis is a process of glucose formation from non-carbohydrate sources such as lactate, amino acids and glycerol. The main initiating point of gluconeogenesis is pyruvate, and many reactions occurring from this point to glucose are identical to those seen in glycolysis. However, gluconeogenesis also requires four new reactions to bypass the irreversibility of the respective glycolysis reactions.
4) In the pentose-phosphate pathway, NADPH and ribose-5-phosphate are produced in cellular cytosol. NADPH is used in various biosyntheses, and ribose-5-phosphate in the synthesis of RNA, DNA and nucleotide coenzymes.
5) Glycogenesis is a series of reactions in which glycogen is being synthesized from glucose. Glycogen is stored in hepatocyte and muscle cell cytosol, where it serves as the body's glucose reserve.
6) Glycogenolysis is a process of glycogen degradation, which proceeds in a reverse sequence of glycogenesis reactions. The glucose-6-phosphate thus formed can be included in the process of glycolysis, whereas in hepatocytes and renal cells it is translated into free glucose that enters the blood.

Carbohydrate metabolism regulation
Various endocrine gland hormones, vitamins and nervous system are involved in the regulation of carbohydrate metabolism.
Insulin enables the entry of glucose into the cells, its storage in the liver in the form of glycogen, and its breakdown to CO2 and water. The action of glucagon, adrenaline, cortisol, growth hormone and thyroxin is reverse to that of insulin, as they tend to increase the blood concentration of glucose. Glycogenolysis is stimulated by glucagon and adrenaline, and gluconeogenesis by cortisol, whereas growth hormone shows an insulin antagonist action at many sites.

Hormones involved in blood glucose regulation.

HormoneBlood glucoseMechanism of action
Inhibition of gluconeogenesis (liver)Glucose entry stimulation (muscle)
InsulinStimulation of glycogenesis (liver, muscle) 
Adrenaline Stimulation of glycogenolysis (liver, muscle)
GlucagonStimulation of glycogenolysis (liver)Stimulation of gluconeogenesis (liver) 
Cortisol Stimulation of gluconeogenesis (liver)
Growth hormone Mobilization of triglycerides


Fasting glucose concentration in the blood of adults is maintained within the range from 3.8 to 6.6 mmol/L by the concert action of all regulatory mechanisms. After a carbohydrate rich meal, glucose concentration in the blood of healthy individuals increases to a maximum of 9 mmol/L. Excess glucose quickly enters the cells, where it is used for energy production or is stored in the form of glycogen or is transformed to fat. If the blood concentration of glucose decreases due to starvation, it will be readily normalized by intrahepatic glycogenolysis and gluconeogenesis.
Thus, the states of normoglycemia, hyperglycemia and hypoglycemia are differentiated according to blood glucose concentration.

1. Normoglycemia is a state in which fasting glucose concentration in the blood is between 3.3 and 6.1 mmol/L.
2. Hyperglycemia is a state in which the blood concentration of glucose exceeds 6.1 mmol/L. The state is characteristic of patients with diabetes mellitus, those taking high amounts of carbohydrates or receiving intravenous glucose, those with severe stress or following cerebrovascular injuries.
3. Hypoglycemia is a state in which the blood concentration of glucose falls below 2.2 mmol/L, and is caused by the administration of insulin or other antidiabetic agents, by starvation or an individual's reaction to certain substances (e.g., reactive hypoglycemia).