Digestion

Digestion is the chemical breakdown of the ingested food into absorbable molecules. Absorption refers to the movement of nutrients, water, and electrolytes from the lumen of the small intestine into the cell, and then into the blood. In this article, we will look at the digestion and absorption of carbohydrates, protein, and lipids.

Carbohydrates Digestion

There are three carbohydrate products which are absorbed by the small intestine; glucose, galactose, and fructose.

Digestion of starch is initiated in the mouth, facilitated by salivary amylase. The majority of carbohydrate digestion occurs in the stomach and duodenum. The main enzyme is pancreatic amylase, which yields disaccharides from starch by digesting the alpha 1-4 glycosidic bonds. The diasaccharides produced (alpha-dextrinase, maltase, and sucrase) are all converted to glucose by brush border enzymes.

Disaccharides occurring naturally in food do not require amylase to break them down. Brush border enzymes (lactase, sucrase, trehalase) hydrolyse these compounds into molecules of glucose, galactose, and fructose.

Absorption

Glucose and galactose are absorbed across the apical membrane by secondary active transport (along with Na+) through the Sodium-Glucose cotransporter (SGLT1). Both glucose and galactose exit the cell via GLUT2 receptors across the basolateral membrane into the blood. Fructose enters the cell by facilitated diffusion via GLUT5 and is transported into the blood via GLUT2 receptors.

Protein Digestion

Protein digestion begins in the stomach with the action of pepsin, which breaks protein into amino acids and oligopeptides. The process of digestion is completed in the small intestine with brush border and pancreatic enzymes. They split the oligopeptides into amino acids, dipeptides and tripeptides.

Absorption

Amino acids are absorbed via a Sodium cotransporter, in a similar mechanism to the monosaccharides. They are then transported across the basolateral membrane via facilitated diffusion. Di and tripeptides are absorbed via separate H+ dependent cotransporters and once inside the cell are hydrolysed to amino acids.

Lipids Digestion

Lipids are hydrophobic and thus are poorly soluble in the aqueous environment of the digestive tract. Their digestion is started by lingual and gastric lipases, but this only digests 10% of ingested lipids.

The remainder of the lipids are digested in the small intestine. Here, bile aids digestion by emulsifying the fat goblets into smaller chunks, called micelles, which have a much larger surface area.

Pancreatic lipase, phospholipase A2, and cholesterol ester hydrolase (3 major enzymes involved in lipid digestion) hydrolyse the micelles, breaking them down into fatty acids, monoglycerides, cholesterol, and lysolecithin.

Absorption

The products from digestion are released at the apical membrane and diffuse into the enterocyte. Inside the cell, the products are re-esterified to form the original lipids, triglycerides, cholesterol, and phospholipids. The lipids are then packaged inside apoproteins to form a chylomicron. The chylomicrons are too large to enter circulation, so they enter the lymphatic system via lacteals.

Digestion

The goal of carbohydrate digestion is to break down all disaccharides and complex carbohydrates into monosaccharides for absorption, although not all are completely absorbed in the small intestine (e.g., fiber). Digestion begins in the mouth with salivary amylase released during the process of chewing. There is a positive feedback loop resulting in increased oral amylase secretion in people consuming diets high in carbohydrates. The amylase is synthesized in the serous cells of the salivary glands. Amylase breaks starches into maltose and polysaccharides. Amylase is sensitive to pH and thus is inhibited in the acidic environment of the stomach. Only 5% of starch is broken down by salivary amylase due to limited exposure. Salivary amylase has increased importance in two groups; infants with decreased pancreatic amylase production in the first 9 months and children with pancreatic insufficiency from cystic fibrosis or other etiologies.

Minimal carbohydrate digestion occurs in the stomach due to the inactivation of amylase in the acidic environment. Pancreatic amylase is released from acinar cells into the small intestine in concert with other enzymes under the stimulus of secretin and CCK and continues the process of carbohydrate digestion. Amylase targets the α-1,4 bonds of complex carbohydrates and is unable to break terminal bonds or α-1,6 bonds. Starch is digested in the small intestine to simple components derived from branched amylopectin (maltose, maltotriose, and α-limitdextrins). Oligosaccharides and disaccharides are digested by specific enzymes in the microvillus membrane (brush border).

Brush border enzymes are synthesized in the endoplasmic reticulum and glycosylated in the Golgi apparatus of the enterocyte. They are then trafficked to the apical membrane where they are anchored at the surface by a transmembrane segment. The anchored enzymes are active following cleavage of a small residue at the extracellular N-terminal end. Disaccharidases are protected from proteolysis by glycosylation and are found in higher concentration in villus enterocytes of the proximal small bowel. These enzymes include maltase (digests maltose to glucose and glucose), sucrase (digests sucrose to fructose and glucose), trehalase (digests trehalose to glucose and glucose), lactase (digests lactose to galactose and glucose) and isomaltase (de-branching enzyme digests α1,6 bonds of limit dextrin to produceglucose). Glucose does not require any additional digestion. The rate-limiting step for absorption differs among the carbohydrates. Sucrose uptake is regulated after hydrolysis by the apical membrane uptake rate of fructose and glucose, whereas lactose absorption is limited by the rate of hydrolysis.(See Figure 2)

Humans born full-term have a full complement of disaccharidases at delivery. However, disaccharidase levels vary during gestation: sucrase appears early (by about 20 weeks), while lactase does not achieve “normal” levels until the 3rd trimester. In most humans, lactase decreases with age starting at about 3-5 years or earlier depending on the population. This pattern has been termed lactase non-persistence. However, in people of Northern European ancestry and other population groups in small areas elsewhere in the world, lactase activity remains at the infantile level. This is termed lactase persistence. Lactase non-persistence is found in the United States mainly in African-Americans, Asians, and Native Americans, although people of Southern European ancestry can also exhibit lactase non-persistence. Lactase activity is “hard-wired” genetically; lactase is not inducible, and lactose restriction does not lower lactase levels. Carbohydrates not digested in the small intestine pass into the large intestine where they are digested by colonic bacteria. This results in the release of short chain fatty acids (SCFA) (propionate, butyrate and acetate) along with methane. The SCFA provide vital nutrition to colonocytes, but excess volumes induce diarrhea and abdominal cramping.

Clinical correlation – Disaccharide deficiency results in symptoms due to an increased osmotic load in the small intestine and frequently elevated short-chain fatty acid (SCFA) production in the colon. The presence of SCFA and their contribution to colonocyte health must also be remembered in children with diversion colitis, which is due to an absence of SCFA.

Absorption

Once carbohydrates are digested, the products must be absorbed and transported to the portal circulation. Digestion and absorption are typically coupled, with the enzymes closely located to the appropriate transporters. Glucose absorption occurs in the small intestine via the SGLT-1 transporter (sodium-glucose co-transporter). Fructose absorption is completed via the GLUT5 transporter by facilitated diffusion.

Glucose and galactose are actively transported from the small intestine lumen by the sodium-glucose transporter (SGLT-1) located in the brush border of the small intestine. The transporter is more prevalent in the duodenum and jejunum. Glucose transport is driven by a sodium gradient across the apical cell membrane generated by the Na+,K+-ATPase pump located in the basolateral membrane of the enterocyte.