Carbohydrate digestion is the process by which, in the gastrointestinal tract, polysaccharides, essentially starch, oligosaccharides, and disaccharides, the latter consisting mainly of sucrose and lactose, are hydrolysed into their constituent monosaccharides, glucose, fructose and galactose, which are subsequently absorbed.[1]
Carbohydrate digestion begins in the oral cavity and continues in the subsequent parts of the digestive tract, particularly in the small intestine, through reactions catalysed by glycosidases, hydrolytic enzymes produced by the salivary glands, the exocrine pancreas, and enterocytes.[2]
The absence or deficiency of one or more of these enzymes can lead to malabsorption, osmotic-fermentative diarrhoea, and other intestinal symptoms.[3]
Summary: Key Points
- Definition: a hydrolytic process by which polysaccharides, oligosaccharides, and disaccharides are cleaved into their constituent monosaccharides (glucose, fructose, and galactose) for intestinal absorption.
- Starch digestion: begins in the oral cavity (salivary α-amylase) and continues in the small intestine (pancreatic α-amylase), hydrolyzing internal α-(1→4) glycosidic bonds to yield maltose, maltotriose, and α-limit dextrins.
- Brush border enzymes: specific α-glucosidases (sucrase-isomaltase, maltase-glucoamylase, and trehalase) localized on enterocytes that finalize the digestive process.
- Lactase exception: lactase is the only β-glycosidase encoded by mammals, specifically responsible for hydrolyzing the β-(1→4) glycosidic bond of lactose.
- Clinical and physiological significance: enzyme deficiencies or genetic defects (such as primary hypolactasia or congenital sucrase-isomaltase deficiency) allow undigested carbohydrates to reach the colon, where they are fermented into gas and short-chain fatty acids, potentially leading to osmotic-fermentative diarrhea.
Contents
Carbohydrate digestion: starch
Starch, a polysaccharide consisting mainly of amylose and amylopectin, is the most abundant and widespread form of carbohydrate and energy storage.[4]
Its digestion occurs via reactions catalysed by α-amylase (EC 3.2.1.1). The enzyme is secreted both by the parotid glands (and to a lesser extent by the submandibular glands), where it is known as salivary α-amylase or ptyalin, and by the exocrine pancreas, where it is known as pancreatic α-amylase.[2]
α-Amylases are endoglycosidases that randomly hydrolyse the internal α-(1→4) glycosidic bonds within the chains of both amylose and amylopectin. The products of the hydrolysis reactions are:
- maltose, from amylose and amylopectin;
- maltotriose, a trisaccharide consisting of three glucose units, from amylose and amylopectin;
- α-limit dextrins, or α-dextrins, which derive almost exclusively from amylopectin;
- small amounts of glucose, from amylopectin.[5][6]
α-Limit dextrins are branched oligosaccharides formed from several glucose molecules linked by α-(1→4) glycosidic bonds and at least one α-(1→6) bond. Those composed of 5–6 glucose units constitute about one third of the final product.[1]
Mouth and stomach
The digestion of starch begins in the mouth thanks to salivary α-amylase. It follows that chewing and the time food spends in the mouth, however relatively brief, are the primary factors influencing the interaction between the enzyme and the starch, and which can improve digestion.[2]
The action of salivary α-amylase is also responsible for the sweet taste experienced when chewing carbohydrate-rich foods for a long time, thus allowing the enzyme time to act.[7]
Once in the stomach, which essentially acts as a reservoir, gastric acidity inactivates salivary α-amylase, whose optimal pH is around 7. The presence of starch can partially protect the enzyme from gastric degradation, allowing it to pass into the duodenum, where it works alongside pancreatic α-amylase.[8]
Whilst the intestinal action of salivary α-amylase is of minimal importance in adults, it can be of some benefit in newborns, and particularly in preterm infants. In fact, during the first few months of life in preterm infants, the production of pancreatic α-amylase is reduced. However, given the low concentration of salivary α-amylase in the intestinal lumen, it is recommended to avoid starch in the diet until the infant is at least six months old.[9]
Small intestine
In the small intestine, bicarbonate ions, secreted by the pancreas in response to the hormone secretin, neutralise gastric acidity. The pH of the intestinal lumen reaches approximately 7, an optimal value for the action of the pancreatic enzymes involved in carbohydrate digestion, namely residual salivary α-amylase, pancreatic α-amylase and the enzymes of the brush border of the enterocytes.[2]
The digestion of starch continues largely through the hydrolytic action of pancreatic α-amylase. In response to meals, this enzyme is secreted in quantities far exceeding digestive requirements, at least 10 times the amount required for optimal digestion of the polysaccharide.[1]
Pancreatic α-amylase acts mainly in the polar phase of the intestinal contents, although some also binds to the intestinal mucosa at the brush border. According to some studies, this topographical arrangement may be advantageous as it would result in the release of starch breakdown products at the lumen-membrane interface of the enterocyte, where the final stage of digestion takes place via the enzymes of the brush border.[10]
The ileum, the terminal part of the small intestine, is capable of continuing carbohydrate digestion and absorbing their products, although to a lesser extent than the duodenum and the jejunum. In the event of disease affecting the jejunum or surgical removal of the upper part of the small intestine, the ileum adapts to the new condition and takes on an important role in both the digestion of carbohydrates and the absorption of monosaccharides.[2]
Final stage of carbohydrate digestion
The final stage of carbohydrate digestion takes place in the small intestine and is carried out by glycosidases produced by enterocytes and located on the surface of the cells’ brush border.[2]
The glycosidases present in the mammalian intestine are almost all specific for α-glycosidic bonds, and include sucrase-isomaltase (EC 3.2.1.48), maltase-glucoamylase (EC 3.2.1.20 for maltase activity and EC 3.2.1.3 for glucoamylase) and trehalase (EC 3.2.1.28). These hydrolases, all of which are glycoproteins, act on the products of α-amylase action and on other non-monosaccharide carbohydrates introduced through the diet, essentially the disaccharides lactose and sucrose, and more rarely trehalose.[6]
An exception is lactase (EC 3.2.1.108), the only mammalian hydrolase involved in carbohydrate digestion that is specific for the β-(1→4) glycosidic bond in lactose.[11]
The ability to synthesise these enzymes is acquired during foetal life, prior to birth, and newborns therefore possess them.[12]
The products of the catalytic activity of the aforementioned α-glycosidases and lactase, namely glucose, fructose and galactose, are absorbed and released into the bloodstream to be distributed to the liver and then to other tissues.[13]
Sucrase-isomaltase
Sucrase-isomaltase is a bifunctional enzyme with two active sites.[14]
One active site exhibits sucrase activity and is specific for the glycosidic bonds in sucrose, maltose and linear oligosaccharides comprising up to 6 glucose molecules.[15] With regard to maltose, sucrase accounts for 60–80% of intestinal maltase activity. The enzyme is therefore an efficient maltase, but owes its name to its ability, unique amongst intestinal enzymes, to hydrolyse the α,β-(1→2) glycosidic bond in sucrose.[16]
The other active site, isomaltase, is capable of hydrolysing the α-(1→6) glycosidic bond in α-limit dextrins; it is therefore an α-1,6-glycosidase, unique amongst the intestinal enzymes involved in the digestion of carbohydrates. Given its specificity for the α-(1→6) bond and the possible use of isomaltose as a substrate, the enzyme is called isomaltase; however, as isomaltose is not one of the products of the action of α-amylase on amylopectin, it is also known as α-dextrinase.[15][16]
As sucrase-isomaltase possesses the enzymatic activities of sucrase, maltase and isomaltase, the enzyme results in the release of glucose and fructose.[13]
Congenital sucrase-isomaltase deficiency is a rare genetic disorder resulting from more than twenty mutations that can affect both sucrase and isomaltase activity.[17]
Maltase-glucoamylase
The enzyme, which exhibits high specificity for the α-(1→4) glycosidic bond, has two active sites. One active site is located in the N-terminal domain and is specific for maltose, whilst the other, situated in the C-terminal domain, has a broader substrate specificity and acts on oligosaccharides comprising between 4 and 9 glucose molecules.[18][19]
The activity of maltase-glucoamylase leads to the release of glucose molecules.[13]
Congenital maltase-glucoamylase deficiency is a relatively rare condition, of which only a few cases are known.[20]
Trehalase
The enzyme, which exists in humans in two isoforms, is specific for the α,α-(1→1) glycosidic bond in trehalose and leads to the release of the two glucose molecules that make up the disaccharide.[13]
Mutations in the genes encoding the two isoforms of trehalase result in the synthesis of enzymes with reduced or absent function.[21]
Lactase
Lactase is the only digestive β-glycosidase encoded in the mammalian genome capable of hydrolysing the β-(1→4) glycosidic bond in lactose to yield galactose and glucose.[11]
Like sucrase-isomaltase and maltase-glucoamylase, it has two active sites: one hydrolyses the β-(1→4) glycosidic bond, whilst the other hydrolyses phlorizin and glycosylceramides (glycolipids). The second active site therefore exhibits phlorizin hydrolase activity, which is why the enzyme is also known as lactase-phlorizin hydrolase.[13]
Lactase appears approximately 8 weeks after conception, being the last of the disaccharidases to develop. With the exception of congenital lactose intolerance, a rare autosomal recessive condition characterised by a complete absence of lactase activity from birth, lactase activity is high and abundant in the mid-jejunum, and remains so for the first four years of life.[22][23]
In adults, a genetically programmed decline in lactase activity, known as primary hypolactasia, is frequently observed; this condition affects around three-quarters of the world’s population.[24]
In cases of intestinal disease, lactase is generally the first of the brush border glycosidases to be lost, a condition that results in secondary hypolactasia. This is due to the fact that the enzyme is expressed at a late stage of enterocyte differentiation, when the cell is close to the tip of the villi; furthermore, it protrudes significantly into the intestinal lumen.[24]
| Stage and Localization | Enzyme | Linkage Specificity | Substrates | Products |
|---|---|---|---|---|
| Luminal Phase (Oral cavity and intestinal lumen) |
Salivary α-amylase | Endoglycosidase; specific for α-(1→4) glycosidic bonds. Inactivated by gastric acid pH. | Starch | Maltose, maltotriose, α-limit dextrins, and traces of glucose. |
| Pancreatic α-amylase | Endoglycosidase; specific for internal α-(1→4) glycosidic bonds. Active at neutral pH (~7) stimulated by bicarbonate. | Starch in the lumen of the duodenum and jejunum. | Maltose, maltotriose, α-limit dextrins, and traces of glucose. | |
| Membrane phase (Enterocyte brush border) |
Sucrase-isomaltase complex | Bifunctional enzyme: – sucrase site: hydrolyzes α-(1→4) and α-(1→2) linkages; – isomaltase site (α-dextrinase): hydrolyzes α-(1→6) linkages. |
Sucrose, maltose, linear oligosaccharides, and α-limit dextrins. | Glucose and fructose. |
| Maltase-glucoamylase | Bifunctional enzyme with high specificity for α-(1→4) glycosidic linkages: – N-terminal domain: specific for maltose; – C-terminal domain: acts on oligosaccharides. |
Maltose and oligosaccharides (4–9 units) derived from amylase activity. | Glucose molecules. | |
| Trehalase | Specific for the α,α-(1→1) glycosidic linkage. | Trehalose | Two glucose molecules. | |
| Lactase | The only mammalian β-glycosidase involved in carbohydrate digestion. Features two catalytic sites: – β-(1→4) glycosidic site; – phlorizin hydrolase site. |
Lactose, phlorizin, and glycosylceramides. | Galactose and glucose. |
Glycosidase deficiency and clinical outcomes
Medical conditions that cause a loss of glycosidases in the intestinal lumen, or mutations in the genes encoding these enzymes that result in the synthesis of enzymes with reduced or absent function, lead to undigested carbohydrates reaching the colon, where they are fermented by the gut microbiota. This leads to the production of gas and short-chain fatty acids, which can contribute to osmotic-fermentative diarrhoea and other abdominal symptoms.[3]
Deficiencies resulting from intestinal infections gradually resolve once the condition returns to normal.[25]
| Enzyme | Deficiency type | Etiology and pathogenetic mechanism | Clinical manifestations |
|---|---|---|---|
| Lactase | Congenital deficiency | Rare autosomal recessive genetic disorder. | Severe watery diarrhea and dehydration from the first days of life following ingestion of breast milk or lactose-containing formula. |
| Primary hypolactasia | Genetically programmed reduction of enzyme expression, affecting approximately 75% of the global adult population. | Lactose maldigestion, abdominal bloating, cramps, flatulence, and osmotic-fermentative diarrhea. | |
| Secondary hypolactasia | Damage to the intestinal mucosa (e.g., celiac disease, infectious gastroenteritis). Lactase is expressed at late stage of enterocyte differentiation and is the first brush-border enzyme to be lost. | Transient lactose intolerance symptoms that resolve upon restoration of the intestinal mucosa. | |
| Sucrase-Isomaltase | Congenital deficiency | Rare autosomal recessive genetic disorder. | Severe sucrose and dextrin malabsorption after weaning, watery diarrhea, abdominal pain, vomiting, and failure to thrive in infants. |
| Maltase-Glucoamylase | Congenital deficiency | Extremely rare hereditary condition. | Reduced tolerance to starches and oligosaccharides, with diarrhea and abdominal distension following meals rich in complex carbohydrates. |
| Trehalase | Trehalase deficiency | Genetic mutations or individual variations leading to poor or absent enzyme activity. | Trehalose intolerance with abdominal symptoms (diarrhea, cramps, flatulence) typically triggered by the ingestion of edible mushrooms. |
References
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- ^ van der Maarel M.J., van der Veen B., Uitdehaag J.C., Leemhuis H., Dijkhuizen L. Properties and applications of starch-converting enzymes of the alpha-amylase family. J Biotechnol 2002;94(2):137-55. doi:10.1016/s0168-1656(01)00407-2
- ^ Lebenthal E. Role of salivary amylase in gastric and intestinal digestion of starch. Dig Dis Sci 1987;32(10):1155-7. doi:10.1007/BF01300204
- ^ Asanuma-Date K., Hirano Y., Le N., et al. Functional regulation of sugar assimilation by N-glycan-specific interaction of pancreatic α-amylase with glycoproteins of duodenal brush border membrane. J Biol Chem 2012;287(27):23104-18. doi:10.1074/jbc.m111.314658
- ^ a b Zecca L., Mesonero J.E., Stutz A., Poirée J.C., Giudicelli J., Cursio R., Gloor S.M., Semenza G. Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the role of the pancreas in pro-LPH maturation. FEBS Lett 1998;435(2-3):225-8. doi:10.1016/s0014-5793(98)01076-x
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- ^ Hunziker W., Spiess M., Semenza G., Lodish H.F. The sucrase-isomaltase complex: primary structure, membrane-orientation, and evolution of a stalked, intrinsic brush border protein. Cell 1986;46(2):227-34. doi:10.1016/0092-8674(86)90739-7
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Domande Frequenti
Where does carbohydrate digestion begin in humans?
It begins in the mouth via salivary α-amylase, which hydrolyses α-(1→4) glycosidic bonds in starch into maltose, maltotriose, and α-limit dextrins. Its catalytic action is inactivated by acidic gastric juice in the stomach before the chyme moves into the small intestine.
Which enzymes complete small intestinal digestion?
Pancreatic α-amylase and brush-border glycosidases: sucrase-isomaltase, maltase-glucoamylase, trehalase, and lactase. They break down remaining starch, oligosaccharides and disaccharides into absorbable monosaccharides (glucose, fructose, and galactose) for release into the bloodstream.
What makes intestinal lactase a unique glycosidase?
It is the sole mammalian β-glycosidase involved in carbohydrate digestion, specifically cleaving the β-(1→4) bond in lactose. Featuring dual catalytic sites (lactase and phlorizin hydrolase), it is also the first brush-border enzyme to be lost during intestinal mucosal injury.
What happens when brush-border glycosidase enzymes fail?
Undigested carbohydrates pass into the colon, where gut microbiota ferments them into gas and short-chain fatty acids. This pathogenetic mechanism draws water into the intestinal lumen, causing abdominal cramps, bloating, flatulence, and osmotic-fermentative diarrhoea.