5 Digestion and Absorption of Carbohydrates

  • To understand the breakdown of complex carbohydrates by hydrolysis.
  • To appreciate the anatomical features of the intestine facilitating nutrient absorption.
  • To appreciate the critical roles of enzymes and transporters for nutrient absorption.
  • To understand the principles of enzymatic catalysis.
  • Hydrolysis of complex carbohydrates
  • Design of the intestinal epithelium
  • Nutrient absorption
  • Enzymatic catalysis

Before discussing the details of digestion and absorption of carbohydrates let us have an overview first (Fig. 1). After a meal and breakdown of complex carbohydrates into glucose and other types of sugars, the individual sugars are absorbed in the intestine and subsequently reach the liver through the portal vein. Here glucose is stored as glycogen and excess sugar converted to fat, which is than transported to adipose tissue. Most of the glucose passes through the liver and reaches other organs through blood circulation. Glucose is taken up by muscle tissue, where it is also stored as glycogen. Brain, heart and erythrocytes have a constant demand for glucose. In the pancreas, glucose triggers the release of insulin the major hormone that increases utilisation and storage of glucose after a meal. 

Fig. 1: Flow of glucose after a meal

Our main carbohydrate sources are starch, sucrose and lactose. Starch is found in all staple foods, such as potatoes, pasta, bread, rice. Sucrose is found in fruits and lactose in milk. Our digestive tract is designed to breakdown carbohydrates in several steps (Fig. 2).

Fig. 2: Step-wise digestion of carbohydrates in the digestive tract.

All complex carbohydrates are stable at room temperature (think caster sugar, potato starch) and their breakdown needs to be catalysed by enzymes (see Enzymes as catalysts below). These enzymes are made by the pancreas and released into the small intestine upon food intake. Amylase initiates the breakdown by hydrolysing alpha-1,4-bonds between glucose units (called glycosidic bonds), generating
alpha-dextrins, maltotriose, maltose and isomaltose (Fig. 3). These smaller saccharides can be hydrolyzed by maltase and isomaltase. The disaccharide sucrose is broken down by sucrase into fructose and glucose. The enzyme is located at the surface of intestinal epithelial cells. Similarly, lactose is hydrolysed by lactase at the surface of enterocytes.

Fig. 3 Enzymatic breakdown of starch occurs in several steps.

The enzymatic activity of saliva is very small, its purpose is to generate a taste sensation rather than being the first step in the digestive process. Digestion of starch and sugars is very fast. You can measure an increase of plasma glucose within 15 min after ingestion of carbohydrates. Watch the video below to appreciate the anatomy of the intestine, which facilitates the absorption of nutrients (Fig. 4).

The important role of digestive enzymes in the breakdown of carbohydrate is illustrated by lactose intolerance. Lactose intolerance is frequently found in countries that do not use a lot of milk products for adult nutrition. There is no mutation underlying the disorder, but rather expression of the enzyme ceases after milk-based infant food is replaced by normal adult nutrition. The symptoms are caused by the bacterial breakdown of lactose, which results in the production of large amounts of lactate in the large intestine, which in turn cause reverse osmosis and water loss. This results in bloating, diarrhoea, flatulence and pain. 

Fig. 4 Structure of the intestine. The surface of the intestinal canal is amplified by protrusions and folds, which have small finger-like processes called villi. Each villus is covered by a layer of epithelial cells, which absorb nutrients. In between goblet cells are found, which produce mucus. The absorbing epithelial cells are called enterocytes, which at the apical surface have smaller finger-like protrusions of the membrane called microvilli. Collectively, the microvilli are called the brush border. Each villus is furnished with blood vessels and vessels of the lymphatic system.

After the digestion process, the resulting sugars are absorbed by the epithelial cells of the intestine. As discussed in chapter 6, lipid membranes are impermeable to polar solutes, which includes sugars. Transporters are embedded in the apical and basolateral membrane to facilitate movement of sugars from the lumen of the intestine to the blood (Fig. 4 and 5). Glucose is transported together with a Na+ (more on transporters in chapter 6), allowing uphill movement of glucose, because the intracellular concentration of Na+ is maintained at about 1/10 of the extracellular concentration by the action of the Na+-K+-ATPase.  Thus, the downhill gradient of Na+ drives the uphill movement of glucose. Once accumulated inside the enterocyte, glucose is released through the basolateral membrane by a facilitated diffusion mechanism, which equilibrates intracellular and extracellular concentrations. Because glucose has been accumulated inside the cell it passively exits the cell because of a downhill gradient. At very high levels of carbohydrate ingestion, further transport capacity is brought into the apical membrane that also uses a facilitated diffusion mechanism. Fructose is entirely transported by facilitated diffusion, because its concentration in blood is low. Also depicted are the enzymes that breakdown disaccharides sucrose and lactose.

Fig. 5 Epithelial transport of sugars.

The importance of intestinal sugar transport is illustrated by the rare disease glucose-galactose malabsorption. It is caused by mutations in the apical glucose/galactose transporter SGLT1. The mutations render the transporter incapable of transporting glucose and galactose. As a result both sugars progress into the distal sections of the intestine. There they are metabolised by the intestinal microflora into lactate, butyrate, acetate generating a large osmotic load in the lumen of the intestine that is higher than the osmolarity of the blood plasma. Reverse osmosis occurs dragging water out of the body resulting in life threatening diarrhoea. Fructose absorption is unaffected, illustrating the existence of a separate transport pathway for this carbohydrate. 

Interestingly, glucose transport helps absorbing water. Glucose is an osmolyte which drags water along when it is absorbed. The glucose transporters itself also facilitates water transport.  During oral rehydration therapy, glucose is provided together with salt to help retain water. This is used when diarrhoea is caused by infection of the intestine with pathogenic bacteria or viruses, when infusion is not readily available. Oral rehydration therapy has saved countless lives from organ failure due to dehydration (Fig. 6).

Fig. 6 Oral rehydration therapy is used in many underdeveloped countries.

There are a number of carbohydrates we cannot digest, particularly cellulose, but also hemicelluloses and pectins. These types of carbohydrates are collectively called fiber. Fiber plays an important role in our nutrition. It supports the intestinal microflora, which metabolizes these carbohydrates into organic acids, such as acetate, propionate, butyrate and lactate. Acetate, propionate and butyrate are called short-chain fatty acids (SFCA). Short-chain fatty acids are an important nutrient for the cells of the colon, which receive very little other nutrients because they are absorbed in the small intestine (Fig. 7). Butyrate in particular is not only a nutrient, but also a differentiation factor that changes epigenetic signatures inside colonocytes and keeps these cells differentiated. Lack of fiber in the nutrition is thus associated with a higher likelihood of colon cancer. Colon cancer is an example of a cancer that is influenced by nutrition.

Probiotics are mixtures of bacteria and yeasts that can be taken as a supplement to improve the intestinal microbiome. Prebiotics are food components or supplements that we cannot digest but can serve as nutrients for the intestinal microflora in the colon.

Fig. 7 Fibre is an important part of our nutrition. It supports the bacterial microflora and indirectly feeds colonocytes.

Cats do not prefer sweet food over savoury or unflavoured food. It turns out that cats do not have a functional receptor for “sweet” taste. The receptor is still found at the surface of the tongue but is non-functional. Other mammalian species with similar mutations in the sweet taste receptor are the sea lion, fur seal, Pacific harbor seal, Asian otter, spotted hyena, fossa and banded lingsang. These species are exclusive meat eaters. In contrast, intact sweet receptor genes were found in the aardwolf, Canadian otter, spectacled bear, raccoon and red wolf. These species include both exclusive meat-eaters and those that also eat other foods in addition to meat. Thus loss of sweet taste receptors can happen in the absence of selective pressure to maintain the gene as it occurs in species that eat carbohydrates.  Proc Natl Acad Sci U S A. 2012; 109(13):4956-61: Major taste loss in carnivorous mammals.

Enzymes as catalysts

Through case studies we have seen how essential enzymes are to break down nutrient polymers. In the absence of enzymes, nutrients are not hydrolysed and are eventually broken down by bacteria. Thus we need to understand how enzymes can facilitate reactions.

A useful analogy to the enzymatic hydrolysis of a disaccharide, is the breaking of a metal stick (Fig. 8). To make the analogy a bit more realistic the metal stick is rather fragile. In order to break the stick, we have to bend it, which requires energy (activation energy) (A). If enough energy is available, the stick breaks. Let us assume a protein, which binds the straight stick very tightly with small magnets (blue) (B). In this case nothing will happen because the ground state of the substrate will be preserved. The substrate has fallen into an energy trap (yellow line in the reaction coordinate, this is not a useful enzyme. Now we assume a protein that binds the bent stick very well (C). The magnets attract the stick, but in the process it gets bent. This is called the transition state, a conformation in which the substrate has the best fit for the active site and is in transit to be converted into the product. Now a small vibration is enough and the stick breaks. The interaction between enzyme and substrate has reduced the activation energy, by forcing the substrate into the transition state. The reaction coordinate shows that the products have a lower energy than the substrate (as is the case for 2 glucose molecules vs 1 molecule of maltose). As a result, the overall reaction is favourable. However, the stick is stable without the presence of an enzyme, due to the activation energy (blue line in the reaction coordinate). This concept is called metastability i.e. the molecule is stable in the absence of a catalyst, but its decomposition is energetically favourable. Please note that the blue line in the reaction coordinate depicts the mean energy of all molecules. In reality each particle has a slightly different energy (see the striped range of energies at the beginning of the reaction coordinate in C). There are always some particles with enough energy to break in the presence of an enzyme, but not in the absence.

Fig. 8: An analogy to explain enzyme catalysis

How does an enzyme look like at the molecular level? In Figure 9 the active site of human Maltase-Glucoamylase (PDB 2QLY) is shown with a substrate analogue. The substrate lies close to the surface; the right end of the substrate disappears in a small cavity. The main tools to break the glycosidic bond are two aspartate residues located on either side of the molecule (in blue).

Fig. 9: Human Maltase with a non-hydrolysable substrate analogue (golden) in the active site. The key catalytic residues are shown next to the substrate.

In Figure 10 the mechanism is shown. One aspartate residue is deprotonated (anionic, base), the other is protonated (acid). The deprotonated aspartate has a free electron pair that attacks the glycosidic bond and forms a covalent intermediate (1). The release of the second glucose unit is facilitated by the donation of a proton from the second aspartate residue (2), which is in the protonated state (neutral, acid). In the final step of catalysis a water molecule comes in (3), hydrolyses the covalent intermediate and restores the protonated state of the aspartate residue. Like any good catalyst, the enzyme is restored after the reaction and can undergo a new cycle (4).

Fig. 10 Enzymatic hydrolysis of disaccharides.

In this enzyme we have already encountered several principles of enzyme catalysis that are listed in Table 1.   We will come across other examples in other chapters. 

Type of catalysis Chemical action
General base
Free electron pair acts as a nucleophile
General acid
Donation of a proton
Covalent intermediate
Substrate forms a covalent intermediate with enzyme, typically after a nucleophilic attack.
Metal ion
Metal ion participates in the reaction. It can act as an acid and attract electrons.
Orientation, proximity
Precision binding of substrate to allow close contact with critical residues and to favour the transition state.
  • Starch, lactose and sucrose are the main types of nutritional carbohydrates. These are hydrolysed by enzymatic processes resulting in glucose, fructose and galactose.
  • The enzymes to break down carbohydrates are secreted by the pancreas into the small intestine or are embedded in the brush border of intestinal enterocytes.
  • Glucose, fructose and galactose are absorbed by enterocytes using specific transport processes in the apical and basolateral membranes.
  • Lack of enzymes to break down lactose (lactose intolerance) or of transporters to absorb glucose and galactose (glucose-galactose malabsorption) illustrate the importance of these proteins in the digestion and absorption process. The transport of glucose together with sodium ions helps with the absorption of water by the intestine and is used in oral rehydration therapy.
  • Enzymes facilitate chemical reactions at body temperature and thus allow the breakdown of otherwise stable molecules. They reduce the activation energy of a reaction by a number of key principles involving  general base, general acid, covalent intermediates and metal ions to facilitate the reaction. The orientation and proximity of the substrate with respect to active site residues is essential for efficient catalysis. 
  1. Fig. 1 By the author
  2. Fig. 2 By the author
  3. Fig. 3 By the author using ChemDraw
  4. Fig. 4 By Openstax  via Creative Commons Attribution 4.0 License. 
  5. Fig. 5 By the author using ChemDraw
  6. Fig. 6 By Olle Gustavsson [CC BY-SA 4.0  (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons
  7. Fig. 7 By the author using Powerpoint
  8. Fig. 8 By the author, inspired by Nelson and Cox Principles of Biochemistry
  9. Fig. 9 By the author using PyMol
  10. Fig. 10 By the author using ChemDraw