Carbohydrates Metabolism

Carbohydrates are the major source of energy Major pathways for the living cells. As such, carbohydrates are the first cellular constituents, synthesized by green plants during photosynthesis from carbon dioxide and water, on absorption of light. Thus, light is the ultimate source of energy for all biological processes. 

The monosaccharide glucose is the central molecule in carbohydrate metabolism since all the major pathways of carbohydrate metabolism are connected with it. Glucose is utilized as a source of energy, it is synthesized from non-carbohydrate precursors and stored as glycogen to release glucose as and when the need arises. The other monosaccharides important in carbohydrate metabolism are fructose, galactose and mannose. 

The fasting blood glucose level in normal individuals is 70-100 mg/dl (4.5-5.5 mmol/l) and it is very efficiently maintained at this level. Liver plays a key role in monitoring and stabilizing blood glucose levels. Thus liver may be appropriately considered as glucostat monitor. 

Major pathways for carbohydrates metabolism

The important pathways of carbohydrate metabolism are listed-

1. Glycolysis (Embden-Meyerhof pathway) : The oxidation of glucose to pyruvate and lactate. 

2. Citric acid cycle (Krebs cycle or tricarboxylic acid cycle) : The oxidation of acetyl CoA to CO2. Krebs cycle is the final common oxidative pathway for carbohydrates, fats or amino acids, through acetyl CoA. 

3. Gluconeogenesis : The synthesis of glucose from non-carbohydrate precursors (e.g. amino acids, glycerol etc.). 

4. Glycogenesis : The formation of glycogen from glucose. 

5. Glycogenolysis : The breakdown of glycogen to glucose. 

6. Hexose monophosphate shunt (pentose phosphate pathway or direct oxidative pathway) : This pathway is an alternative to glycolysis and TCA cycle for the oxidation of glucose (directly to carbon dioxide and water). 

7. Uronic acid pathway : Glucose is converted to glucuronic acid, pentoses and, in some animals, to ascorbic acid (not in man). This pathway is also an alternative oxidative pathway for glucose. 

8. Galactose metabolism : The pathways concerned with the conversion of galactose to glucose and the synthesis of lactose. 

9. Fructose metabolism : The oxidation of fructose to pyruvate and the relation between fructose and glucose metabolism. 

10. Amino sugar and mucopolysaccharide metabolism : The synthesis of amino sugars and other sugars for the formation of mucopoly- saccharides and glycoproteins. 

Entry of glucose into cells 

Glucose concentration is very low in the cells compared to plasma (for humans < 100 mg/dl). However, glucose does not enter the cells by simple diffusion. Two specific transport systems are recognized for the entry of glucose into the cells 

1. Insulin-independent transport system of glucose : This is a carrier mediated uptake of glucose which is not dependent on the hormone insulin. This is operative in hepatocytes, erythro- cytes and brain. 

2. Insulin-dependent transport system : This occurs in muscle and adipose tissue. 

Glucose transporters : In recent years, at least six glucose transporters (GLUT-1 to GLUT-5 and GLUT-7) in the cell membranes have been identified. They exhibit tissue specificity. For instance, GLUT-1 is abundant in erythrocytes whereas GLUT-4 is abundant in skeletal muscle and adipose tissue. 

Insulin increases the number and promotes the activity of GLUT-4 in skeletal muscle and adipose tissue. In type 2 diabetes mellitus, insulin resistance is observed in these tissues. This is due to the reduction in the quantity of GLUT-4 in insulin deficiency. 

GLYCOLYSIS 

Glycolysis is derived from the Greek words (glycose—sweet or sugar; lysis—dissolution). It is a universal pathway in the living cells. The complete pathway of glycolysis was elucidated in 1940. This pathway is often referred to as Embden-Meyerhof pathway (E.M. pathway) in honour of the two biochemists who made a major contribution to the knowledge of glycolysis. 

Glycolysis is defined as the sequence of reactions converting glucose (or glycogen) to pyruvate or lactate, with the production of ATP. 

Salient features of Glycolysis

1. Glycolysis takes place in all cells of the body. The enzymes of this pathway are present in the cytosomal fraction of the cell. 

2. Glycolysis occurs in the absence of oxygen (anaerobic) or in the presence of oxygen (aerobic). Lactate is the end product under anaerobic condition. In the aerobic condition, pyruvate is formed, which is then oxidized to CO2 and H2O. 

3. Glycolysis is a major pathway for ATP synthesis in tissues lacking mitochondria, e.g. erythrocytes, cornea, lens etc. 

4. Glycolysis is very essential for brain which is dependent on glucose for energy. The glucose in brain has to undergo glycolysis before it is oxidized to CO2 and H2O. 

5. Glycolysis (anaerobic) may be summarized by the net reaction 

Glucose + 2ADP + 2Pi 2Lactate + 2ATP 

6. Glycolysis is a central metabolic pathway with many of its intermediates providing branch point to other pathways. Thus, the intermediates of glycolysis are useful for the synthesis of amino acids and fat. 

7. Reversal of glycolysis along with the alternate arrangements at the irreversible steps, will result in the synthesis of glucose (gluconeogenesis).