Class Notes

Carbohydrate Digestion and Absorption

Dr. V. Ganapathy, Medical College of Georgia
Biochemistry, Lecture 9
September 16th, 2005

An average daily intake of 350-400g of carbohydrates is normal for adults.
Most (sixty percent of the total) dietary carbohydrate is a polysaccharide (a large number of sugar residues linked together in a chain) known as starch.
- Amylose, a straight-chain polymer of glucose, makes up twenty percent of starch.
- Amylopectin, a branched-chain polymer of glucose, makes up eighty percent of starch.
Sucrose, a disaccharide (two sugar molecules, glucose and fructose, attached together), makes up thirty percent of the total intake.
Lactose, or milk sugar, is a disaccharide of galactose and glucose, and makes up ten percent of the total.
Other sugars, such as fructose (a monosaccharide) enter into the diet in smaller amounts.

Glucose is an aldose, containing a terminal aldehyde group.
Under normal conditions, the aldehyde group will combine with the fifth carbon forming a cyclic structure called a lactone ring.
The anomeric carbon (carbon 1) can exist in the ring with its hydroxyl group below the plane (α) or above the plane (β).
Amylose is built by α (alpha)-1,4 glycosidic linkages, meaning that glucose is present in the α (alpha) form, with a glycosidic bond forming between carbon 1 (the anomeric carbon) of one monomer and carbon 4 of the next.
Amylopectin possesses branch points via α (alpha)-1,6 linkages, with the anomeric carbon of the monomer beginning the new chain attached to the sixth carbon (the carbon not included in the ring) of a glucose residue present in the straight chain, via a glycosidic bond.

Sucrose is a dimer of fructose and glucose (a disaccharide).
β (beta)-fructose and α (alpha)-glucose are the anomers present in sucrose.
Fructose has the same empirical formula, but is an isomer of it. The fructose ring is five-membered (pentagonal) rather than six-membered (hexagonal), since fructose is a ketose (containing a ketone group at carbon 2 rather than an aldehyde group at carbon 1).
α (alpha)-fructose bears the largest group of its anomeric carbon (carbon 2) below the plane, while β (beta)-fructose bears it above the plane of the ring.
Sucrose is formed by a glycosidic linkage between the anomeric carbons of the two monomers.

Lactose is a dimer of galactose (another isomer of glucose) and glucose.
β (beta)-galactose and α (alpha)-glucose attach via a β (beta)-1,4 glycosidic linkage.

Glycogen is a more highly-branced glucose polymer than amylopectin, and does not exist in a straight-chain form.
Glycogen is used for energy storage in animals, and enters the diet by meat and liver.

Cellulose is a linear glucose polymer containing glucose residues connected with β (beta)-1,4 linkages. Since humans do not have an enzyme which hydrolyzes such bonds, cellulose is an indigestible carbohydrate.
Dietary fiber (ingested cellulose) has beneficial effects in the colon. Intestinal flora can digest cellulose to glucose. Glucose produced in the colon is of no use to us, since the colon does not have any glucose transport system. However, "feeding" the bacteria with cellulose produces other beneficial effects, since glucose fermentation products — the short-chain fatty acids acetate (CH₃COOH), propionate (CH₃CH₂COOH), and butyrate (CH₃(CH₂)₂COOH) — are the preferred energy source for colonocytes. Thus, the connection between fiber intake and colonic health.

Luminal digestion occurs in the lumen of the small intestine, while membrane digestion occurs in contact with the membranes of cells lining the lumen of the intestine.

Luminal digestion of starch and glycogen is primarily mediated by salivary and pancreatic amylase (from the duodenal pancreatic duct of the exocrine pancreas), since it hydrolyzes both α (alpha)-1,4.
Salivary amylase acts mainly in the mouth and esophagus, since it performs maximally at pH 7. Pancreatic amylase is able to perform well at the lower pH of the small intestine.
Amylase is an endoglycosidase, meaning that it cannot hydrolyze terminal glycosidic linkages.
The two limitations of amylase result in the digestion of starch to maltose (glucose α-1,4 disaccharide), maltotriose (glucose α-1,4 trisaccharide), and short-branched oligosaccharides, α-limit dextrins (around the branch points of amylopectin and glycogen).

Small sugars (maltose, maltotriose, alpha-limit dextrin, sucrose, and lactose) require further hydrolysis before use.
Enterocytes (microvilli-bearing cells lining the small intestine) have two major membrane regions: the brush-border membrane, which increases the absorptive surface area of the cell in contact with the lumen, and the basolateral membrane, which is made up of the basal and lateral portions of the membrane, and is in contact with the blood supply and with neighbouring cells.
Membrane digestions takes place on the brush-border membrane of enterocytes, mediated by lactase (hydrolyzes lactose to galactose and glucose), sucrase-isomaltase (hydrolyzes sucrose to glucose and fructose, maltose to glucose, and α-limit dextrin to maltose), and glucoamylase (hydrolyzes maltose and maltotriose to glucose).
Glucose, galactose, and fructose produces by membrane digestion remain in the lumen until translocated into the cytosol by transporters.

Transporters are integral membrane proteins.
SGLT1 (Sodium/Glucose Costransporter 1) is brings two sodium ions into the cell for every glucose or galactose translocated. SGLT1 is electrogenic, producing membrane depolarization. (SGLT1 is a secondary active transporter, utilizing the electrochemical Na⁺ gradient to provide energy to move glucose against its concentration gradient.
The Na/K pump on the basal membrane of the cell hydrolyzes ATP to export three sodium ions and bring two potassium ions in at the same time, supporting repolarization of the cell (since the cytosol contains one fewer positive charges per cycle of the pump).
Fructose transport is mediated by GLUT5 (glucose transporter 5, similar structurally to many glucose transporters), a facilitative transporter.
Glucose, galactose, and fructose are exported to the bloodstream via GLUT2 (a facilitative transporter) in the basal membrane.

Mutations in SGLT1 result in an inability to utilize dietary starch, glycogen, lactose, and sucrose, since all three contain glucose. Dietary glucose sources cause complications (such as osmotic diarrhoea; and intestinal bloating, flatus, and hydrogen gas on the breath due to bacterial fermentation of glucose and galactose) due to high glucose levels in the colon. Fructose is the only carbohydrate tolerated by patients with this disorder. However, between the ages of five and ten years, for unknown reasons, glucose tolerance (and possibly utilization) develops.

Dairy products are the most prevalent source of lactose, and as long as patients avoid such foods, complications are minimal or absent. Infant lactose malabsorption is usually congenital. Later-developing lactose intolerance is usually also genetic in nature, but results due to a different mechanism.