L6- Digestion and Absorption of Carbohydrates

Question 1

LO1: Digestion/absorption of dietary carbs- define key reactions/phases

Answer 1

DIGESTION
oral cavity- oligosaccharide fragments generated
small intestine- pancreatic phase
mucosal brush border cells- disaccharide phase

ABSORPTION
Upper jejunum- lumen into intestinal mucosal cell, or intestinal cytosol into portal circulation

Question 2

LO1: Digestion/absorption of dietary carbs- define key enzymes and hormones

Salivary alpha-amylase
Secretin/CCK
Pancreatic alpha-amylase
Dextrinase
Maltase
Lactase
Isomaltase/sucrase

Answer 2

1. salivary alpha-amylase (endogluosidase): cleaves internal alpha (1-4) glucosidic bonds of glycogen, amylose and amylopectin
2. secretin/cholecystokinin (CCK): hormones that initiate pancreatic phase (secretin stimulates pancreatic juices which are high in bicarb; CCK stimulates pancreatic alpha-amylase and other digestive enzymes)
3. pancreatic alpha-amylase: cleaves alpha-(1,4) glucosidic bonds to generate maltose, glucose, and limit dextrins (alpha-1,6 bonds)
4. dextrinase: embedded in the glycocalyx; cleaves the alpha-(1,6) bonds of the limit dextrins
5. Maltase: alpha-glucosidase that hydrolyzes maltose to 2 molecules of glucose
6. lactase: beta-galactosidase that cleaves lactose to galactose and glucose
7. isomaltase/sucrase: double headed enzyme; one domain hydrolyzes sucrose to fructose and glucose while the other domain hydrolyzes isomaltose to 2 molecules of glucose

Question 3

LO1: Digestion/absorption of dietary carbs- define key proteins (membrane,glycoproteins, transport)

Answer 3

1. integral membrane proteins: disaccharidases located as these in mucosal brush border cells (active in disaccharide phase)
2. glycoproteins: make up extracellular layer called the glycocalyx, which is where the disaccharides are embedded to extend into the lumen
3. intestinal hexose transporters: SGLT1, GLUT5, GLUT2

Question 4

LO2: Lumen vs. brush border (phases of carbohydrate digestion in small intestine)

Answer 4

LUMEN
1. pancreatic phase: secretin/CCK release (to stimulate bicarb and neutralize acidic chyme/to stimulate pancreatic alpha-amylase to digest oligosaccharides)

BRUSH BORDER
1. disaccharide phrase: disaccharidases digested by disaccharidases which are embedded in the glycocalyx as integral membrane proteins (maltase, lactase, isomaltase/sucrase, dextrinase)

Question 5

LO3: Compare/contrast glucose transport mechanisms in brush border vs. basolateral membrane

Answer 5

BRUSH BORDER MEMBRANE (transport from lumen into intestinal cell)

• Sodium-dependent glucose transporter (SGLT1): high affinity for glucose, co-transports Na+ and D-glucose or D-galactose (energy provided by Na+ gradient)
• Fructose transporter (GLUT5): transports fructose

BASOLATERAL MEMBRANE (transport from intestinal cytosol to portal circulation)

-Sodium-independent glucose transporter (GLUT2): high capacity and low affinity for glucose; transports glucose, galactose, and fructose

Question 6

LO4: What tissues exhibit insulin-dependent uptake of glucose and why?

Answer 6

• Fat cells, skeletal muscle, and heart muscle
• GLUT4 transporters localized here; glucose transport by these transporters stimulated by insulin (insulin signals recruitment of GLUT4 transporters from ER and Golgi body into the plasma membrane
• insulin released in response to elevated blood glucose, so these transporters aid in uptake of glucose for purpose of storing and/or using excess glucose

Question 7

LO5: Explain structure/function relationship of GLUT transporters in liver, muscle, and brain

Answer 7

Liver glucose transporter: GLUT2

• low affinity and high capacity for glucose transport
• not stimulated by insulin
• not dependent on Na+ gradient
• allows “glucose sensing” f(x) as transport depends on gradient of free glucose inside vs. outside the cell

Muscle glucose transporter: GLUT4

• stimulated by insulin (released when glucose is in excess)
• allows glucose to rapidly enter tissues when it is in excess (transporters upregulated in plasma membrane when insulin is present)

Brain glucose transporters: GLUT1 in BBB’s endothelial cells, GLUT3 in neurons

• neither are stimulated by insulin
• GLUT1: high affinity and high capacity for glucose transport, saturated at physiological glucose concentrations which ensures constant supply of glucose
• GLUT3: highest affinity and capacity/rate of transport out of all the GLUT isozymes, so glucose supply to brain is high even when blood glucose is low

Question 8

LO6: How can hyperglycemia in diabetes lead to cataracts, nephropathy, and neuropathy?

Answer 8

1. When glucose is in excess, it is common for glucose to get converted to sorbitol by aldol reductase
2. Aldol reductase is expressed in retina, lens, kidney, and nerve cells
3. Aldol reductase has high Km for glucose, so sorbitol production significant when glucose is above normal physiological levels (as in diabetes)
4. Glucose transporters that aren’t dependent on insulin are present in retina, lens, and nerve cells, so cellular uptake is proportional to plasma glucose concentration (will take up more glucose when glucose levels are high, doesn’t matter if insulin is present or not)
5. Accumulation of sorbitol causes osmotic effects that contribute to tissue damage, presenting as cataracts, blidness, nephropathy, and neuropathy