digestion and absorption

Question 1

1. Describe the mechanisms and identify the sites of carbohydrate digestion as well as the proteins involved in carbohydrate absorption by enterocytes.

Answer 1

• Only monosaccharides (ex: fructose, glucose, galactose) can be absorbed by GI tract; therefore oligosaccharides and polysaccharides must first be broken down into monosaccharides before they can be absorbed. Fiber cannot be digested or absorbed by the human GI tract.
• Key sites of carbohydrate digestion & proteins involved:
  o Lumen of intestine: alpha-amylase (note: this enzyme is also produced in the saliva of the oral cavity but plays a much smaller role in carbohydrate digestion).
   Function: break polysaccharides into oligosaccharides.
  o Brush border (small intestine): lactase, maltase, and isomaltase.
   Function: break oligosaccharides into monosaccharides.
• Absorption by enterocytes:
  o SGLT1: moves glucose and galactose across luminal membrane. It is a cotransporter, so it also absorbs sodium from GI lumen.
  o Simple diffusion: fructose can diffuse through luminal membrane.
  o GLUT2: moves glucose, galactose, and fructose across basal membrane of enterocytes (maintains concentration gradient).

Question 2

2. Describe the mechanisms and identify the sites of protein digestion as well as the proteins involved in protein absorption by enterocytes.

Answer 2

• Oligopeptides AND amino acids can be absorbed by gut (unlike carbohydrates). Therefore, proteins do not need to be broken down all the way to amino acids in order to be absorbed.
• Key sites of protein digestion & proteins involved:
  o Lumen of stomach: pepsin.
   Function: breaks proteins into oligopeptides.
  o Lumen of duodenum: trypsin and brush border peptidases:
   Function: break oligopeptides into smaller oligopeptides/amino acids.
• Absorption:
  o PEPT1: peptide transporter I: cotransporter of small oligopeptides and H+ across luminal membrane of enterocytes.
  o Amino acid transporter B: cotransporter of peptides and Na+ across luminal membrane of enterocytes.
  o Note: amino acid transporter B and SGLT1 are referred to as “nutrient-coupled sodium transporters” (both are Na+/nutrient symporters).

Question 3

3. Describe the mechanisms and identify the sites of lipid digestion as well as the mechanism for absorption of lipids and fat soluble vitamin by enterocytes.

Answer 3

• Key sites of lipid digestion & proteins involved:
  o Lumen of stomach: lingual lipase, gastric lipase, emulsification:
   Function: break down lipids (triglycerides and cholesterol) into triglycerides, diglycerides, free fatty acids, and cholesterol.
   Note: primary function of stomach in terms of lipid digestion is mechanical, not chemical; simply breaks lipid droplets down into smaller lipid droplets.
  o Lumen of duodenum: pancreatic lipase, co-lipase, emulsification; along with bile:
   Function: primary site of lipid digestion, mediated by pancreatic lipase; converts larger lipid droplets  small lipid droplets  “micelles”, which are absorbable collection of bile salt, fatty acids, di- and tri-glycerides, etc.
   Note: co-lipase has no enzymatic activity of its own; it just activates lipase so it can bind and digest triglycerides into fatty acids and diglycerides.
• Absorption:
  o Micelle falls apart at surface of luminal epithelium due to changes in pH.
  o Component of micelle can then diffuse across luminal membrane or are taken up via facilitated uptake (via NPC1L1).
  o Inside enterocytes: everything is put back together to form chylomicrons.
  o Chylomicrons transported across basal membrane of enterocytes.

Question 4

4. Describe the mechanism and identify the sites of absorption for water soluble vitamins and minerals (folic acid, vitamin B12, calcium, and iron).

Answer 4

• Folic acid:
  o Site of absorption: duodenum.
  o Mechanism: exchange protein expressed on surface of enterocytes.
  o Note: folic acid is important for DNA synthesis and cell division; impaired folic acid uptake results in impairment of blood cell proliferation (anemia).
• Vitamin B12:
  o Site of absorption: ileum.
  o Mechanism: intrinsic factor secreted by parietal cells of stomach  IF and B12 form complex in duodenum  taken up by receptor-mediated process in ileum  vitamin B12 binds to carrier protein  complex is secreted into blood and taken up by liver for storage.
• Calcium:
  o Site of absorption: duodenum, absorptive enterocytes.
  o Mechanism: absorptive enterocytes express calcium channel for uptake of calcium.
  o Note: expression of calcium channel is regulated at level of gene transcription by vitamin D. No vitamin D  no calcium channel  hypocalcemia.
• Iron:
  o Site of absorption: small intestines.
  o Mechanism: iron is maintained in absorbable form by vitamin C  complexes with transferrin in intestine (secreted by intestinal cells)  receptor-mediated internalization of transferrin-Fe2+ complex (similar to uptake of vitamin B12). Can also be taken up by divalent cation transporter 1 (DCT1)  transferred into blood  complexes with plasma transferrin  carried to liver.

Question 5

5. Know and understand the following pathophysiological conditions and symptoms: lactose intolerance, celiac sprue, and pernicious anemia.

Answer 5

• Lactose intolerance:
  o What it is: inability to breakdown and absorb lactose.
  o Causes: normal physiological decline in lactase levels expressed on brush border cells (note: lactase breaks lactose down into glucose and galactose so they can be absorbed by SGLT1).
  o Disease process: lactose not taken up  fluid retention in intestines  diarrhea. Also, lactose broken up by intestinal bacteria  release of CO2 gas  bloating, cramping, etc.
• Celiac sprue, aka gluten-sensitive enteropathy:
  o What it is: loss of mature villous duodenal and jejunal epithelium following ingestion of gluten.
  o Causes: hyperactive immune response stimulated by gluten (gluten is seen as “foreign” by immune system, and is thus attacked causing damage to villi of small intestine).
  o Disease process: cell death of intestinal epithelial cells  shortening of villi  reduction in surface area of small intestines  decreased absorptive capacity of small intestine.
• Pernicious anemia:
  o What it is: vitamin B12 deficiency.
  o Causes: atrophy (usually associated with aging) of gastric mucosa and parietal cells  decreased/no intrinsic factor production  decreased vitamin B12 absorption  decreased # of blood cells but increase in size (without division)  megaloblastic anemia.
   Note: vitamin B12 and folic acid are both important for normal proliferation of blood cells.