Flashcards in sakai-Digestion and absorption Deck (40)
A child suffering from protein malnutrition can show a plump belly. Why?
The plump belly is due to lack of the protein albumin. Albumin is used in the blood as transport protein but it is also needed and essential for osmolality.
Albumin synthesis needs amino acids, and the edema seen in this patient is the result of a diet deficient in proteins.
Should an individual suffering from gout eat a diet low in purine bases or a diet low in pyrimidine bases? Why?
Individuals suffering from gout show high uric acid levels in the blood, and crystals can form that trigger a gout attack.
They should eat a diet low in purine bases, as the dietary purine bases are degraded to uric acid in intestinal mucosal cells before reaching the blood. This can increase the uric acid concentration in blood even more in addition to the formed uric acid in the liver.
Pyrimidine bases are degraded or taken up into the liver and are harmless for individuals suffering from gout.
How do dietary essential fatty acids and fat-soluble vitamins reach the liver? How do medium-chain fatty acids reach the liver? Which nutrient is rich in medium-chain fatty acids?
Dietary essential fatty acids and fat-soluble vitamins reach the liver via chylomicron remnants.
The dietary essential fatty acids fall into the group of long chain fatty acids (16-20 carbons) , and they are found esterified in TAGs or cholesteryl esters (CEs) inside the chylomicrons. They can also be esterified in phospholipids of the phospholipids monolayer of lipoproteins.
Medium-chain fatty acids are released from intestinal mucosal cells directly as
free fatty acids into the portal vein and reach the liver.
Medium-chain fatty acids are found in TAGs of milk and this food source allows
the rapid uptake into the liver for energy metabolism.
Also, TAGs with medium-chain fatty acids can be degraded by lingual and gastric
lipase which do not need bile salts for activity.
Why would the deficiency of conjugated bile salts lead to gallstones and also to less digestion of lipids?
A deficiency of conjugated bile salts can lead to gallstones, which are commonly composed of cholesterol.
Cholesterol is released from the liver into bile, and bile contains bile salts and phosphatidylcholine to keep the free cholesterol in solution.
Another important function of conjugated bile salts is emulsification of dietary lipids. Bile salts are needed for lipid digestion for the action of pancreatic lipase and of pancreatic phospholipase A2.
Last but not least, bile salts are also needed for the uptake of the digested lipids into intestinal mucosal cells.
Describe the action of gastrin! In which cell types is gastrin formed? From which cell type is gastric acid (HCL) released?
Gastrin is a hormone that leads to release of gastric acid (HCl) from parietal cells into the lumen of the stomach.
Gastrin is formed by G cells at the bottom of the gastric gland.
What is the action of salivary -amylase in the mouth and what happens in the stomach?
Salivary amylase cleaves -(1-4) sugar bonds. This enzyme is active in the mouth, but it is inactivated in the stomach by high proton concentration. The high proton concentration in the stomach lumen also denatures dietary proteins and nucleic acids and can destroy bacteria.
Are lingual lipase and gastric lipase active at low pH? Which lipids are preferably cleaved by these enzymes?
Lingual lipase (swallowed with the food) and gastric lipase are active a low pH.
[Not many enzymes are active at low pH, the other enzyme that is active in the stomach is pepsin for protein degradation.]
Lingual lipase and gastric lipase act mainly on TAGs with medium-chain fatty acids, as found in milk.
Describe the activation of pepsinogen to pepsin! Which cells release pepsinogen?
Pepsinogen is activated to pepsin by acid catalyzed cleavage at high proton concentration, as found in the lumen of the stomach.
In addition, pepsin can cleave pepsinogen, and as a result all pepsinogen is
rapidly activated once it is in contact with the normal stomach acid.
Pepsinogen is released by chief cells, these cells also release gastric lipase.
Does pepsin act mainly as an exopeptidase or an endopeptidase?
Pepsin acts mainly as endopeptidase, which means that it cleaves proteins from the inside and leads to smaller proteins and peptides.
What happens when too much antacid drugs are taken? What results from reduced acid production in some patients or the elderly?
Antacid drugs increase the pH in the stomach juice, and this can lead to less activation of pepsinogen to pepsin and in addition to lower activity of the present
pepsin which has a pH 2 optimum.
Reduced acid production also leads to an increase in pH and reduced digestion
of proteins. This is common in the elderly.
What activates the release of secretin and cholecystokinin? Which cells form these hormones?
The high proton concentration of chyme which is released into the duodenum activates the release of secretin from endocrine cells of the duodenum.
Cholecystokinin (CCK) is released from intestinal endocrine cells as response to peptides and amino acids formed by pepsin and also as response to fatty acids formed by lingual and gastric lipases in the stomach.
What are the main actions of secretin?
Secretin leads to the release of bicarbonate and water from the pancreas.
It also inhibits to a certain degree the release of chyme from the stomach which
allows time for neutralization of the present chyme so that the food can be further
digested by pancreatic enzymes which need a more neutral pH.
What are the main actions of cholecystokinin (CCK)?
Cholecystokinin got its name from the fact that it leads to release of bile from the gallbladder via contractions.
CCK inhibits gastric motility and production of gastric acid.
CCK also leads to the release of pancreatic enzymes and activation of
enteropeptidase which can activate released trypsinogen, but only in the lumen of
the duodenum. Water is also released by the pancreas.
[Pancreatitis leads to the specific injury markers of pancreatic -amylase and
pancreatic lipase in the blood. Often this is due to ethanol abuse, gallstones or very
high levels of VLDL in the blood (hypertriacylglyerolemia). It is also found in
patients with cystic fibrosis]
Describe pancreatic -amylase! Discuss the name and the bonds that are cleaved by this enzyme. Can humans digest cellulose? Explain.
Pancreatic -amylase cleaves dietary polysaccharides to disaccharides. The enzyme is named after its place of synthesis in the pancreas and it finds its substrate in the duodenum.
Pancreatic -amylase cleaves like salivary amylase (1-4) linkages of sugars in starch and glycogen and forms maltose and isomaltose.
Cellulose has (1-4) bonds which cannot be cleaved by human enzymes (naming: -amylase cleaves -bonds). It is part of fiber that is excreted in feces.
Describe and discuss the pH in the lumen of the stomach, of the small intestine and the pH of the bicarbonate rich pancreatic juice!
The pH in the lumen of the stomach is about pH 2, the pH in the small intestine is neutralized to a higher pH in the range of pH 6-8 by the bicarbonate rich
pancreatic juice which has a pH 8.
How does cystic fibrosis (CF) lead to impaired digestion? What is a clinical sign of patients with CF?
Cystic fibrosis got its name from the cystic fibrosis of the pancreas.
The pancreatic juice lacks water due to the defective release of chloride ions via the specific chloride ion channel CFTR in epithelial cells.
[Note, CFTR does not pump chloride ions, it allows the movement with the concentration gradient once the ABC-transporter forms an open channel.
The chloride ions and water are released from epithelial cells into the pancreatic duct, that means they are not in the ECF but now outside of the body.]
The pancreatic enzymes lead to a protein clot due to the highly viscous mucus. Mostly the digestion of dietary proteins and dietary lipids is diminished.
CFTR in the small intestine is also defective and the feces does not contain enough water for its normal consistency.
CF patients show signs of malnutrition in addition to recurrent lung infections. Both are caused by a deficient release of chloride ions from the epithelium via CFTR and the resulting dried mucus.
[A salty skin of the forehead is the result of a defective re-uptake of chloride ions via CFTR in the sweat gland and is used for diagnosis of CF but is itself not life-threatening. The severe problems result from CFTR in the lung and pancreas and small intestine]
How would you treat patients with cystic fibrosis related to their diet?
Patients with cystic fibrosis suffer from malnourishment due to the lack of pancreatic enzymes and bicarbonate and water. Patients should eat frequently a
The diet could include carbohydrates as even only 10% of the normal amount of pancreatic -amylase is able to digest carbohydrates.
The digestion of dietary lipids is reduced, but triacylglycerols with medium-chain fatty acids as found in milk are already cleaved in the stomach by lingual and gastric lipases. This is not reduced in patients with cystic fibrosis, and in addition,
another advantage is that the generated medium-chain fatty acids can reach directly the liver via the portal vein and can be used for energy metabolism.
Why are the pancreatic proteases synthesized and transported in their inactive zymogen form?
Pancreatic proteases need to be synthesized in the pancreas in their inactive form, otherwise they would cleave the proteins of the pancreas or the pancreatic duct.
[note: snake and bee venoms contain active proteases and phospholipase A which
destroy biological membranes]
What is the action of enteropeptidase? Where is this enzyme synthesized and how is it activated? Why is enteropeptidase not synthesized in the pancreas?
Enteropeptidase has a very specific cleavage site and it can only cleave trypsinogen to trypsin out of the group of zymogens coming from the pancreas.
Enteropeptidase is synthesized by cells of the duodenum, with the purpose that it is not in contact with zymogens of the pancreas until these zymogens reach the intestines.
Enteropeptidase (enterokinase) is bound to the cell membranes and released into the lumen of the duodenum after action of CCK. This ensures that trypsinogen is activated only in the duodenum by proteolysis by enteropeptidase.
[This activation is an irreversible activation by proteolytic cleavage.]
Name seven inactive pancreatic enzymes or proteins that are proteolytically activated by trypsin!
Trypsin activates the inactive proteases trypsinogen, chymotrypsinogen, proelastase, and two procarboxypeptidases. Trypsin cleaves also the protein
procolipase and activates prophospholipase A2.
Why is a trypsin inhibitor protein formed in the pancreas and travels together with trypsinogen to the duodenum? How is trypsin inhibited in the lumen of the intestine?
Trypsin has the capacity to activate pancreatic zymogens of proteases and of phospholipase A, which would lead to acute pancreatitis in the case that trypsin would be active already in the pancreas or pancreatic duct.
This is why an inhibitory protein for trypsin is released from the pancreas together with trypsinogen. In the case that trypsinogen is after all already abnormally activated to trypsin in the pancreas or pancreatic duct, then this inhibitory protein can inactivate trypsin.
Once the trypsinogen inhibitor protein reaches the duodenum, it will be degraded together with dietary proteins as it is not longer needed. In the duodenum, trysinogen is meant to be activated to trypsin and trypsin shall not be inactivated.
[note: this inhibitory protein for trypsin is NOT 1-antitrypsin, which is found in the blood and alveoli of the lung in order to inhibit neutrophil elastase. The naming is misleading as 1-antitrypsin will never be in contact with trypsin in the human body.]
The proteases will eventually degrade each other and also phospholipase A once the dietary protein is degraded. This is why in the lumen of the intestine, we do not need inhibitory proteins for these destructive enzymes. It is also an advantage to take up not only the amino acids from dietary proteins, but also the amino acids from these degraded enzymes, and also amino acids from the fast turnover of mucosal cells.
Name the specific protein cleavage sites of trypsin, chymotrypsin and elastase!
Trypsin cleaves very specifically at the carboxyl site of arginine or lysine
residues, it has a long narrow binding pocket where these long side chains fit in.
The positively charged lysine and arginine residues are held in place by an ionic
bond as the binding pocket of trypsin has a negative charge at the bottom.
Chymotrypsin cleaves after bulky or aromatic amino acid residues, it has a wide
large binding pocket.
Elastase has a small binding pocket and cleaves after amino acid residues with a
small side chain, like glycine, alanine or serine.
[glycine and alanine residues are found in large amounts in elastin]
What is formed by pancreatic phospholipase A2? Explain the name and discuss why this enzyme is soluble.
Pancreatic phospholipase has its name from the origin of its synthesis (it is synthesized in the pancreatic cells as the zymogen prophospholipase).
This phospholipase is of the type A2, which means that it cleaves glycerophospholipids and releases the fatty acyl group of position-2 of the glycerol backbone.
It forms a free fatty acid and a lyso-phospholipid, both molecules have detergent character and can now be used to emulsify dietary lipids.
Pancreatic phospholipase is soluble for the digestive process and shall be only active in the lumen of the intestines. It will be eventually degraded by proteases.
[Most other phospholipases are intracellular enzymes, they are often bound in membranes and their activity is tightly regulated as they are surrounded by their substrates]
Describe pancreatic lipase and its need for colipase and bile salts!
Pancreatic lipase is meant to cleave the large amounts of dietary TAGs. TAGs are the majority of dietary lipids and form lipid droplets. Pancreatic lipase acts on a lipid-water phase.
In order to emulsify TAGs and make smaller droplets, conjugated bile salts are needed, which can interact with their hydrophobic side with the lipid droplet, and with their negatively charged hydrophilic side with the watery phase in the lumen of the intestines. Lyso-PC and free fatty acids and bowel movement improve this process of emusification
Colipase is a protein that allows pancreatic lipase to act on the TAGs of the lipid droplets, it pushes the conjugated bile salts to the side and anchors pancreatic lipase on the lipid-water phase.
Why is there no need to synthesize and transport pancreatic lipase in form of a zymogen?
Pancreatic lipase needs as substrate TAGs, which are not found in large quantity in the normal pancreas.
This enzyme also needs conjugated bile salts in order to emulsify TAGs and also
the protein colipase for anchoring at the lipid-water phase.
Bile salts are not available in the pancreas, they are released by the liver and
reach the duodenum via the bile.
Colipase is still in the state of procolipase, which needs cleavage by trypsin in the
duodenum in order to become colipase.
What is mainly formed by pancreatic lipase? Free glycerol or monoacylglycerol?
Pancreatic lipase has the purpose to form molecules from TAGs that can enter the intestinal mucosal cell. (It does not have the purpose to release all three fatty
When it cleaves TAGs to DAGs, most of the formed DAGs do not enter the intestinal mucosal cells but once pancreatic lipase cleaves the DAGs to MAGs, then this monoacylglycerol is able to enter the intestinal mucosal cell.
With that, there is no need to cleave the fatty acid that is still in 2-monoacylglycerol. It also seems that it is easier for the pancreatic lipase to cleave the fatty acids at the outside of the TAGs (in positions 1 and 3).
Inside the intestinal mucosal cells, TAGs are resynthesized in a specific pathway (MAG pathway) starting with monoacylglycerol. This is a very fast process and needs less enzymes than TAG synthesis performed in most other cells.
Which compound is used for primary bile acid synthesis, and where does this synthesis take place? What are secondary bile acids and how are they formed?
Cholesterol is used in the liver to synthesize primary bile acids, which are cholic acid and chenodeoxycholic acid. Chole is the greek word for bile. This synthesis takes place only in the liver!
Secondary bile acids are generated from primary bile acids later on in the intestine by modification by bacteria.(deoxycholic acid and lithocholic acid)
In which cells are bile acids conjugated and which compounds are used? What is the function of the gallbladder?
The conjugation of bile acids is performed only in the liver. Both primary or secondary bile acids are conjugated and only the “bile salts” are released by the liver into the bile.
Glycine or taurine (formed from cysteine in the liver) are conjugated with bile acids. Conjugated bile acids are often named bile salts, as they will be in the salt form at the pH of the duodenum.
The function of the gallbladder is to store and concentrate the watery bile. Bile contains for example, conjugated bile salts, phosphatidylcholine, free cholesterol and also conjugated bilirubin.
What is the advantage of conjugating bile acids regarding their charge at the pH in the small intestine?
The pKa of cholic acid is pK6, which means that at pH 6 half of the molecules are charged and half are uncharged.
Bile acids show one hydrophobic side and one hydrophilic side in their structure.
It is of advantage to have a charged group in order to improve the hydrophilic interaction with the water phase.
By conjugation with glycine or taurine in the liver, this can be achieved. As a result we find negatively charged molecules at the normal pH(6-7) in the intestinal lumen of the duodenum.
[the pK6 of the unconjugated cholic acid is changed to pK4 for glycocholic acid (cholic acid conjugated with glycine) and to pK2 for taurocholic acid (cholic acid conjugated with taurine), as examples]