METABOLISM OF GLUCOSE
Abbate Spallanzani (1768) showed that living tissues take up oxygen and give off carbon dioxide. In 1860, Louis Pasteur demonstrated the fermentation process of glucose to alcohol by yeast. Fick (1882) indicated that chemical energy in muscle is converted to contraction of the muscle. Gad (1893) found out that lactic acid is formed during muscle contraction. In 1902, Sir Walter Fletcher established that this lactic acid is derived from glycogen. In 1914, Gustav George Embden (1874-1933) studied the lactic acid formation from pyruvate. In 1919, Otto Fritz Meyerhof (1884-1951) enunciated most of the steps of the glycolytic pathway (Nobel prize, 1922). Hexokinase enzyme was first identified by von Euler Chelpin in 1915 (Nobel prize, 1922). Other enzymes in the glycolytic pathway were then identified rapidly; pyruvate decarboxylase by Neuberg in 1911, phospho fructo kinase by sir Arthur Harden in 1920 (Nobel prize, 1929); phospho hexose isomerase by Lohmann in 1933; pyruvate kinase by Parnas in 1934; enolase by Meyerhof in 1935; phospho gluco mutase by Leloir in 1938 (Nobel prize, 1970); glyceraldehyde phosphate dehydrogenase by Warburg in 1939; phosphoglyceromutase by Sutherland in 1942 (Nobel prize, 1971). Between 1935 and 1943, all enzymes of the glycolytic pathway were crystallized and characterized by Warburg. He was awarded the Nobel prize in 1931 for his earlier work on cellular respiration. He was awarded the Nobel prize for the second time in 1944 for his contributions in glycolysis, but Hitler did not permit him to receive it!
Clinical Importance of Glucose
1. Glucose is the preferred source of energy for most body tissues. Brain cells derive energy mainly from glucose.
2. When glucose metabolism is deranged, life-threatening conditions may occur. A minimum amount of glucose is always required for normal functioning.
3. Normal fasting plasma glucose level is 70 to 110 mg/dl. After a heavy carbohydrate meal, it rises; but in a normal person, this level is below 150 mg/dl
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 that is not dependent on the hormone insulin. This is operative in hepatocytes, erythrocytes, 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
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