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Metabolism of carbohydrates

The digestion of carbohydrates involves hydrolysis to liberate oligosaccharides, disaccharides and finally monosaccharides.

Digestion of carbohydrates

Amylases Catalyze the Hydrolysis of Starch

The hydrolysis of starch is catalyzed by salivary and pancreatic amylases, which catalyze random hydrolysis of α (1-›4) glycoside bonds, yielding dextrins, then a mixture of glucose, maltose, and isomaltose (from the branch points in amylopectin).

The process of digestion starts in mouth by salivary alpha amylase, however due to shorter duration of stay of food in mouth, the digestion is left incomplete.

Gastric HCl causes hydrolysis of sucrose, while there is no hydrolytic enzyme present  in gastric juice for the digestion of carbohydrates.

Pancreatic amylase, an isoenzyme of salivary amylase, differs only in the optimum pH of action. Both the enzymes require Chloride ions for their action (Ion activated enzymes).(Figure-1)

Disaccharidases Are Brush Border Enzymes

The disaccharidases, maltase, sucrase-isomaltase (a bifunctional enzyme catalyzing hydrolysis of sucrose and isomaltose), lactase, and trehalase are located on the brush border of the intestinal mucosal cell where the resultant monosaccharides and others arising from the diet are absorbed. In most people, apart from those of northern European origin, lactase is gradually lost through adolescence, leading to lactose intolerance. Lactose remains in the intestinal lumen, where it is a substrate for bacterial fermentation to lactate, resulting in discomfort and diarrhea.

 Figure- 1-  Digestion of carbohydrates proceeds through action of   amylases, dextrinases and disaccharidases. Monosaccharides , the products of digestion  are eventually absorbed in the intestinal mucosal cells.

Absorption of monosaccharides

Only monosaccharides are absorbed  in the intestinal mucosal cells. Minute quantities of disaccharides  absorbed are rapidly eliminated through kidneys.  

The processes involved are-

1) Active transport (Sodium dependent co transport)

2) Facilitated diffusion (Carrier mediated)

3) Passive diffusion 

1) Active transport- Glucose and galactose are absorbed by a sodium-dependent process. They are carried by the same transport protein (SGLT 1), and compete with each other for intestinal absorption. The carrier protein carries sodium along with Glucose. The flow of sodium is down the concentration gradient, while glucose is transported against the concentration gradient. The downward gradient of sodium transport drives the flow of glucose molecules. Sodium is later expelled out by the sodium pump, with utilization of energy.

This type of co transport is also utilized to reabsorb glucose from kidney tubules, involving SGLT2 Transporter. Deficiency of SGLT2 causes Renal Glycosuria  due to failure to reabsorb glucose from tubular filtrate. (Figure-2)

 Figure-2-  The co transport of Glucose is mediated by SGLT-1/2. SGLT-1 are  present on the intestinal cells while SGLT-2 are  present on the surface of proximal tubular cells.

2) Facilitated diffusion- Other monosaccharides are absorbed by carrier-mediated diffusion (Facilitated diffusion). Because they are not actively transported, fructose and sugar alcohols are only absorbed down their concentration gradient, and after a moderately high intake, some may remain in the intestinal lumen, acting as a substrate for bacterial fermentation.

3) Passive diffusion is a very slow process and is of less importance. It is down the concentration gradient, does not involve the transporter or energy expenditure.

The absorbed glucose is transported to portal blood  from intestinal cell by specific GLUT-2 transporters (Facilitated diffusion). (Figure-3)

Figure-3- Showing the absorption of monosaccharides

Disorders of digestion and absorption
1) Lactose intolerance

Answer- Lactose intolerance is caused by a deficiency of lactase enzyme, which is produced by the cells lining the small intestine. Disaccharides cannot be absorbed through the wall of the small intestine into the bloodstream, so in the absence of lactase, lactose present in ingested dairy products remains uncleaved and passes intact into the colon. The operons of enteric bacteria quickly switch over to lactose metabolism, and the resulting in-vivo fermentation produces copious amounts of gas (a mixture of hydrogen, carbon dioxide, and methane). This, in turn, may cause a range of abdominal symptoms, including abdominal cramps, bloating, and flatulence. In addition, as with other unabsorbed sugars (such as Sorbitol, Mannitol, and xylitol), the presence of lactose and its fermentation products raises the osmotic pressure of the colon contents.

The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached. Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit, which increases the degree of maldigestion. The combined increase in fecal water, intestinal transit, and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms.

Classification of Lactose Intolerance

There are three major types of lactose intolerance:

1) Primary lactose intolerance

Primary lactase deficiency develops over time and begins after about age 2 when the body begins to produce less lactase. Most children who have lactase deficiency do not experience symptoms of lactose intolerance until late adolescence or adulthood.

2) Secondary lactose intolerance

Secondary, or acquired, lactase deficiency may develop in a person with a healthy small intestine during episodes of acute illness. This occurs because of mucosal damage or from medications resulting from certain gastrointestinal diseases, including exposure to intestinal parasites such as Giardia lamblia. In such cases the production of lactase may be permanently disrupted. A very common cause of temporary lactose intolerance is gastroenteritis, particularly when the gastroenteritis is caused by rotavirus. Another form of temporary lactose intolerance is lactose overload in infants. Secondary lactase deficiency also results from injury to the small intestine that occurs with celiac disease, Crohn’s disease, or chemotherapy. This type of lactase deficiency can occur at any age but is more common in infancy.

3) Congenital lactase deficiency

It is a genetic disorder which prevents enzymatic production of lactase.  It is present at birth, and is diagnosed in early infancy.


Three tests are commonly used –

1) Hydrogen Breath Test

The person drinks a lactose-loaded beverage and then the breath is analyzed at regular intervals to measure the amount of hydrogen. Normally, very little hydrogen is detectable in the breath, but undigested lactose produces high levels of hydrogen. The test takes about 2 to 3 hours

2) Stool Acidity Test

The stool acidity test is used for infants and young children to measure the amount of acid in the stool. Undigested lactose creates lactic acid and other short chain fatty acids that can be detected in a stool sample. Glucose may also be present in the stool as a result of undigested lactose.

3) Urine test– Besides these tests, urine shows- positive test  with Benedict’s test, since lactose is a reducing sugar and a small amount of lactose is absorbed in the intestinal cell by pinocytosis and is rapidly eliminated through kidneys in to urine.

4) Mucosal biopsy confirms the diagnosis.

Management of lactose intolerance

Although the body’s ability to produce lactase cannot be changed, the symptoms of lactose intolerance can be managed with dietary changes. Most people with lactose intolerance can tolerate some amount of lactose in their diet. Gradually introducing small amounts of milk or milk products may help some people adapt to them with fewer symptoms. Lactose-free, lactose-reduced milk, Soy milk and other products may be recommended. Lactase enzyme drops or tablets can also be consumed. Getting enough calcium is important for people with lactose intolerance when the intake of milk and milk products is limited. A balanced diet that provides an adequate amount of nutrients—including calcium and vitamin D—and minimizes discomfort is to be planned for the patients of lactose intolerance.

 2) Sucrase- isomaltase deficiency– Both enzyme deficiencies are seen together as they are present on the same polypeptide chain

Clinical manifestations are same as lactose intolerance. Mucosal biopsy can confirm the diagnosis.

3) Glucose galactose malabsorption-  Deficiency of SGLT-1,causes  glucose and galactose malabsorption. The sugars are lost in feces.

 Glucose uptake in peripheral tissues

Glucose transporters comprise a family of at least 14 members. The most well characterized members of the family are GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5.  These transporters mediate the thermodynamically downhill movement of glucose across the plasma membranes of animal cells. These are bidirectional; they can transport glucose both into and out of cells and are driven by the concentration gradient. However, export of glucose from tissues to the circulation is limited to organs that produce sugar (liver and kidney) or to organs that receive sugar from the outer milieu (the small intestine). 

The members of this family have distinctive roles:

 1. GLUT1 and GLUT3, present in nearly all mammalian cells, are responsible for basal glucose uptake. Their Km value for glucose is about 1 mM, significantly less than the normal serum-glucose level, which typically ranges from 4 mM to 8 mM. Hence, GLUT1 and GLUT3 continually transport glucose into cells at an essentially constant rate.

 2. GLUT2, present in liver and pancreatic beta cells, are distinctive in having a very high m value for glucose (15 20 mM). Hence, glucose enters these tissues at a biologically significant rate only when there is much glucose in the blood. The pancreas can thereby sense the glucose level and accordingly adjust the rate of insulin secretion. Insulin signals the need to remove glucose from the blood for storage as glycogen or conversion into fat. The high Km value of GLUT2 also ensures that glucose rapidly enters liver cells only in times of plenty.  They are also present on serosal surface of intestinal cells and are involved in transportation of glucose from intestinal cells to portal blood.

 3. GLUT4, which has a Km value of 5 mM, transports glucose into muscle and fat cells. The presence of insulin, which signals the fed state, leads to a rapid increase in the number of GLUT4 transporters in the plasma membrane (Figure-4). Hence, insulin promotes the uptake of glucose by muscle and fat. The number of these transporters present in muscle membranes increase in response to endurance exercise training.


Figure-4-Insulin regulates glucose uptake into these cells (They are present in skeletal, cardiac muscles and adipose tissue) by recruiting membrane vesicles containing the GLUT4 glucose transporters from the interior of cells to the cell surface, where it allows glucose to enter cells by facilitative diffusion.  Once in the cytoplasm, the glucose is phosphorylated and thereby trapped inside cells. The effect of insulin on GLUT4 distribution is reversible. Within an hour of insulin removal, GLUT4 is removed from the membrane and restored intracellular in vesicles ready to be re-recruited to the surface by insulin.  Thus, glucose uptake by muscle and fat cells is regulated by modulating the number of GLUT4 glucose transporters on the surface of cells. 

4. GLUT5, present in the small intestine, testes, seminal vesicles and kidney, function  primarily as  fructose transporters.

5. GLUT 6- is a product of pseudo gene.

6.GLUT-7 – are  present at the surface of endoplasmic reticulum and are  related with perhaps the export of glucose from endoplasmic reticulum to cytoplasm, after the action of glucose-6 phosphatase (Old concept- recently these transporters have been found in the small intestine also)

Clinical significance

There is increased expression of GLUT1 and GLUT3 transporters on the surface of cancer cells. Cancer cells grow more rapidly than the blood vessels to nourish them; thus, as solid tumors grow, they are unable to obtain oxygen efficiently. In other words, they begin to experience hypoxia. Under these conditions, glycolysis leading to lactic acid fermentation becomes the primary source of ATP. Glycolysis is made more efficient in hypoxic tumors by the action of a transcription factor, hypoxiainducible transcription factor (HIF-1). In the absence of oxygen, HIF-1 increases the expression of most glycolytic enzymes and the glucose transporters GLUT1 and GLUT3. In fact, glucose uptake correlates with tumor aggressiveness and a poor prognosis.


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