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Transcript
Questions on Digestion and Absorption
1.
2.
3.
4.
5.
6.
Digestion of carbohydrates in diet.
(3/4)
Describe digestion of starch to glucose.
(3/4)
Describe with the help of a diagram how glucose is absorbed in the intestine. (3)
Describe the absorption of glucose
(3)
Glucose absorption
(3/4)
Explain the mechanism involved in the absorption of glucose. Describe the causes and
features of lactose intolerance.
(3/4)
7. Explain how fructose, glucose and ribose are absorbed from the G.I tract.
(3)
8. Lactose intolerance
(3/4)
9. Write in brief about the digestion and absorption of proteins
(3/4)
10. Describe the process of digestion and absorption of dietary proteins.
(5)
11. Role of hydrochloric acid in protein digestion.
(3)
12. Write in detail about the digestion and absorption of lipids. Write about causes of fatty
stools.
(5)
13. Give an account of the digestion of a triacylglycerol.
(3/4)
14. Write a brief account on absorption of fat from gastrointestinal tract
(3)
15. Functions of bile salts.
(3)
16. Formation and disposal of chylomicrons.
(3/4)
17. What is steatorrhoea? Mention two causes for steatorrhoea.
(3)
18. Explain the biochemical basis: a) Oral insulin is not effective in treating diabetes mellitus.
b) Steatorrhea is observed in chronic pancreatitis.
(3)
19. Explain the biochemical basis: a) Denatured proteins are more easily digested.
b) Steatorrhea in biliary obstruction
(3)
Digestion and Absorption of Food
HPKedilaya,GaneshPrasad
2014……………………………………………………………………………...
Note: Superscript number denotes ‘Reference for further details’ given in a box usually at the
bottom of the page or end of the topic. This is less important for examinations.
Contents:
 Biological Importance
 Medical Importance
 Digestion and Absorption – General Aspects
 Digestion and Absorption of Carbohydrates
 Digestion and Absorption of Proteins
 Digestion and Absorption of Fat
Biological Importance
Digestion is a chemical process wherein large molecules in the food are broken down to smaller
molecules so that they can be absorbed.
Food consists of large molecules which cannot be absorbed by the body as such and hence need
to be digested. Food also consists of small molecules such as vitamins, minerals,
monosaccharides and free amino acids which do not need digestion and can be absorbed as such.
Absorption is transport of molecules, either digested products or other small molecules which
do not require digestion, from the intestinal lumen into blood across the intestinal mucosal
cells.
1
Medical Importance
Lactose intolerance is a condition where intake of milk causes diarrhea and is due to deficiency
of lactase, the enzyme required for digestion of lactose of milk.
Hartnup’s disease is due to a genetic defect in the absorption of neutral amino acids, especially
tryptophan.
Steatorrhea is a condition where excess fat is excreted in feces and is seen in diseases of
pancreas, biliary obstruction, etc.
Chronic diarrhea can cause malabsorption as seen in celiac disease, Sprue, Crohn’s disease,
etc.
Digestion and Absorption – General Aspects
Digestion



The major foodstuffs that require digestion are carbohydrates, proteins and fat
(triacylglycerol).
During the process of digestion macromolecules are broken down to smaller
molecules – polysaccharides to monosaccharides, proteins to amino acids and
triacylglycerols (fats and oils) to glycerol and fatty acids.
Digestion takes place in the aqueous medium of various digestive juices –
Site of Digestion






Digestive Juices
Mouth
Saliva
Stomach
Gastric juice
Small intestinal lumen
Pancreatic juice, Bile and Intestinal juice
Digestion involves action of enzymes that are present in different digestive
juices.
All digestive enzymes are hydrolases that hydrolyze the anhydride linkages –
glycosidic, peptide and ester linkages of carbohydrates, proteins and fats,
respectively.
Bile, synthesized in liver and entering into duodenum, neutralizes acidic stomach
contents when it enters the duodenum providing optimum pH for enzymes in
small intestinal lumen and helps in fat digestion (Bile salts, a constituent of bile,
help in both digestion and absorption of fat.)
During cooking, hydration of polysaccharides and denaturation of proteins take
place. This helps digestion of these molecules.
Mastication helps in breaking down of food particles and thus increases solubility
and surface area for enzyme action.
Peristalsis is also important in breaking down of food particles and mixing them
with enzymes.
Absorption


The small intestine is the main absorptive organ. About 90% of the ingested foodstuffs
are absorbed in the course of passage through the small intestine and water is absorbed at
the same time.
Considerably more water is absorbed after the foodstuff residues pass into the large
intestine, so that the contents, which were fluid in the small intestine, gradually become
more solid in the colon.
2
 Absorption of substances into mucosal cells involves the passage across the plasma
membrane either by – simple diffusion or carrier-mediated transports.
– Simple diffusion is passive (no energy expenditure) and does not require carrier
protein.
– Carrier mediated transports may be facilitated transport (passive) or active
transport (requiring energy expenditure)
 There are two pathways for the transport of materials absorbed by the intestine –
1) The hepatic portal system, which takes absorbed water-soluble nutrients directly
to the liver
2) The lymphatic vessels, which takes absorbed lipid-soluble nutrients in the form
of chylomicrons to the blood stream by way of thoracic duct
Digestion and Absorption of Carbohydrates
Contents:





Introduction
Digestion of Starch (and glycogen)
Digestion of Disaccharides
Absorption of Carbohydrates
Clinical Significance
Introduction
The major carbohydrates in the diet are:

Monosaccharides – mainly fructose (present in fruits)

Disaccharides – sucrose, lactose and small amounts of maltose (present in malt, beer)

Polysaccharides – starch and dietary fibers
Starch forms more than 50% of carbohydrates in human food.
(Dietary fibers – cellulose, hemicellulose, pectin, lignins, etc. are indigestible. For ‘Dietary
fibers’, see Chapters – ‘Chemistry of Carbohydrates’ and ‘Nutrition’)
Human food also contains small amounts of pentoses, glucose, trehalose (disaccharide present in
mushroom), and glycogen (present in liver in animal foods).
All enzymes of carbohydrate digestion cleave glycosidic bonds by hydrolysis.
Disaccharides and polysaccharides are digested to their respective constituent monosaccharides
units and absorbed in the small intestines along with free monosaccharides present in the food.
The absorbed monosaccharides enter the hepatic portal circulation and then to liver cells. Part of
the absorbed monosaccharides that is not taken up by hepatic cells enters the systemic
circulation.
DIGESTION
ABSORPTION (in the Small
Intestine)
Fructose
Fructose
Sucrose
FOOD
Starch
Glucose
3
Lactose
Galactose
Digestion of Starch
1, 2
 Starch on complete digestion yields glucose.
 Digestion of starch takes place in mouth, small intestinal lumen and the small
intestinal brush border (luminal surface of intestinal mucosal cells).
 Enzymes required for complete digestion of starch are – amylase (salivary and
pancreatic amylase), maltase and isomaltase.
 Amylase and maltase cleave -1,4 glycosidic linkages and isomaltase cleaves -1,6
glycosidic linkages of starch. (Amylase hydrolyzes internal -1,4 glycosidic linkages.)
 Starch is mainly digested by pancreatic amylase. Contribution by salivary amylase is very little
since the food remains in the mouth for a very short period of time and the enzyme is inactivated
by gastric HCl as it enters stomach.
 Maltase and isomaltase are present on the luminal surface of small intestinal epithelial cells (brush
border cells).
Starch (amylose and amylopectin)
Salivary amylase (in mouth)3
Or
Pancreatic amylase (in small intestinal lumen)
Limit dextrins4
Small unbranched oligosaccharides (e.g., Maltose, Maltotriose, etc)
Isomaltase
Maltase
Maltase (brush border cells)
Glucose
Isomaltose
Isomaltase (brush border cells)
Reference
1. The enzymes and the steps of digestion of glycogen are same as those of amylopectin
component of starch as both have similar structure.
2. Cooking hydrates the starch granules making it more susceptible to digestion.
3. Salivary amylase (ptyalin) is present in saliva. Cl- is an activator of this enzyme.
4. Limit dextrins are derived from amylopectin component by the action of amylase and
contain eight glucosyl units with one or two branches with α-1,6-glycosidic bonds.
4
Digestion of Disaccharides
–
–
–
Major disaccharides present in the human diet are – sucrose and lactose.
Small amounts of free maltose (present in malt, beer) and trehalose (disaccharide
present in mushroom) may also be present.
However, quantitatively maltose is the major disaccharide digested in the gut. Most
of the maltose in the gut is derived from digestion of starch. Isomaltose is another
disaccharide derived from starch and is digested by isomaltase. (See ‘Digestion of
Starch’).
Site of digestion of disaccharides is the small intestinal brush border.
Maltose, sucrose, lactose and trehalose are digested (hydrolyzed) by
disaccharidases – maltase, sucrase (also called invertase), lactase and trehalase
respectively.
Disaccharidases are attached to the surface of the small intestinal brush border cells.
(For ‘digestion of maltose’, see ‘Digestion of Starch’.)
–
–
–
–
Sucrase
Sucrose
glucose + fructose
Lactase
Lactose
glucose + galactose
Trehalase
Trehalose
2 glucose
Maltase
Maltose
2 glucose
Isomaltase
Isomaltose
2 glucose
Absorption of Monosaccharides




The major monosaccharides resulting from carbohydrate digestion are D-glucose, Dgalactose and D-fructose.
Absorption is carrier mediated.
Pentoses are absorbed by simple diffusion.
Monosaccharides are first transported from the lumen to the small intestinal epithelial
cells and then into capillaries of portal venous system.
Absorption of Glucose
Glucose is absorbed from the small intestinal lumen into the intestinal epithelial cells by carrier
mediated mechanism involving transporter proteins situated on the luminal surface of the
intestinal epithelial cells.
Glucose is absorbed mainly by 1) Na+-dependent transporter by secondary active transport
and to a less extent by 2) Na+-independent transporter by passive transport.
1) Na+-dependent transporter (SGLT)
5
This carrier protein carries glucose or galactose along with sodium ion from the lumen. The
driving force for the Na+-dependent transport is derived from the maintenance of low
intracellular levels of Na+ by the action of the Na+-K+ATPase (secondary active transport).
2) Na+-independent transporter
Small amounts of glucose, is transported by facilitated transport utilizing glucose transporter-5
(GLUT-5).
Transport of glucose from cells to portal venous capillaries:
Glucose is transported from the intestinal epithelial cells into portal venous capillaries by
glucose transporter-2 (GLUT-2).
It is a uniport facilitated transport system, which is sodium independent.
Intestinal Lumen
Glucose
Intestinal
Epithelial Cell
Na
Na+-dependent transporter (SGLT)
GLUT-5
Glucose
+
Na+
K+
ATP
ADP + Pi
Na+
K+
Na+–K+ ATPase
Glucose
GLUT-2
Portal Capillary Blood
Figure: Absorption of Glucose
Absorption of Other Monosaccharides
Fructose is absorbed from small intestinal lumen into mucosal cells by facilitated transporter
GLUT-5, sharing with glucose.
Galactose is absorbed by Na+-dependant trasporter (SGLT) sharing with glucose.
Both fructose and galactose are transported from the intestinal epithelial cells into portal venous
capillaries by glucose transporter-2 (GLUT-2), sharing with glucose.
Any pentose present in food is absorbed by simple diffusion.
Clinical Significance
Lactose Intolerance
6
This is a common condition with gastrointestinal symptoms like diarrhea, abdominal cramps and
flatulence after ingestion of milk or milk-based foods.
Cause is due to deficiency of lactase5.
Deficiency may be due to genetic (primary/inherited) or acquired (secondary to other causes).
The reason for acquired lactose intolerance may be the damage to intestinal epithelial cells due
to colitis, gastroenteritis, alcohol consumption or sudden change into a milk-based diet.
Biochemical basis of clinical manifestation:
Lactase deficiency

Accumulation of lactose, organic acids and gases (CO2 and H2)
(Produced by action of bacteria on lactose in the gut)

Osmotic movement of water from the intestines to the lumen

Flatulence and abdominal cramps
Diarrhea
Treatment involves avoiding milk. Curd is an effective treatment, because the lactobacilli
present in curd contains the enzyme lactase.
Reference
5. If the lactase enzyme is defective at birth then this constitutes early onset lactose
intolerance (inherited lactase deficiency).
A significant number of adults exhibit late onset lactase deficiency (primary low
lactase activity) especially Asian-, Native- and African-Americans.
Digestion and Absorption of Proteins
Contents:




Digestion of protein – general aspects
Reactions of protein digestion
Absorption of amino acids
Clinical significance
Digestion of Proteins – General Aspects
Contents:
–
–
–
–
–
–
Introduction
Sites of protein digestion, GIT juices and proteases
Endopeptidases and exopeptidases
Specificity of proteases
Proteases -zymogen form and activation
Role of HCl in protein digestion
Introduction
7
Digestion of dietary proteins involves hydrolysis of peptide bonds catalyzed by a group of
enzymes called proteases or peptidases in the gastrointestinal tract
Complete digestion of proteins yields amino acids.
Dietary proteins are denatured on cooking and therefore, cooked proteins are more easily
digested1.
Sites of Protein Digestion, GIT Juices and Proteases
 Protein digestion takes place in stomach and intestinal lumen.
 Enzymes of protein digestion are secreted in gastric juice, pancreatic juice and
intestinal juice.
GIT Juices
Proteases Present
Gastric juice
Pepsin (chief cells of stomach), Rennin2
Pancreatic Juice
Trypsin, Chymotrypsin, Elastase. Carboxypeptidases
Intestinal Juice
Aminopeptidases, Dipeptidases
Endopeptidases and Exopeptidases
- Carboxypeptidases and aminopeptidases are exopeptidases – hydrolyze terminal bond
releasing one amino acid at a time. Carboxypeptidases act at the carboxy terminal and
aminopeptidases at the amino terminal of the protein chain.
- Pepsin, trypsin, chymotrypsin, etc are endopeptidases – hydrolyze peptide bonds in the
interior of the protein chain to cleave the protein molecule into more than one smaller
polypeptides and peptides.
Specificity of Proteases
Endopeptidases hydrolyze specific peptide bonds in protein molecules. Specificity differs from
one protease to another3.
Proteases – Zymogen Form and Its Activation
Proteolytic enzymes are secreted as inactive zymogens/proenzymes, which are converted to
their active form in the intestinal lumen4.
Reference
1. During the process of denaturation unfolding of protein molecule takes place and thus peptide
bonds become more accessible for the enzyme action.
2. Rennin, a protease, is active in infants and is involved in curdling of milk. Rennin
denatures casein of milk to paracasein irreversibly, which then is acted upon by pepsin.
Rennin is reported to be absent in the stomach of adults.
3.
Enzyme
Hydrolysis of petide bonds formed by carboxyl groups of
Pepsin
Trypsin
Chymotrypsin
Phe, Tyr, Trp, Met
Arg, Lys (basic amino acids)
Phe, Tyr, Trp, Val, Leu (Aromatic, uncharged amino
8
Acids)
Ala, Gly, Ser (small amino acid residues)
Elastase
4. Activation of enzymes involves the cleavage of small peptides so that the active sites are
exposed. This would prevent auto-digestion of the secretory acini.
Active Enzyme
-
Inactive Zymogen
Pepsin
Pepsinogen
Trypsin
Chymotrypsin
Trypsinogen
Chymotrypsinogen
Elastase
Proelastase
Carboxypeptidase
Procarboxypeptidase
Pepsinogen is activated to pepsin in the stomach first by HCl, secreted by parietal cells
of stomach and then by pepsin itself (autoactivation).
HCl
Pepsinogen
Pepsin
Autoactivation
-
Trypsinogen is activated to trypsin in the small intestine first by enterokinase (a
protease present on the intestinal mucosal membranes) and then by trypsin itself
(autoactivation).
Enterokinase
Trypsinogen
-
Trypsin
Trypsin also catalyses the activation of chymotrypsinogen, proelastase and
procarboxypeptidases to chymotrypsin, elastase and carboxypeptidases, respectively.
Trypsin
Chymotrypsinogen
Chymotrypsin
Proelastase
Elastase
Procarboxypeptidase
Carboxypeptidase
Role of HCl in Protein Digestion
The role of HCl, secreted by gastric parietal cells, in protein digestion are - 1) activation of
pepsinogen 2) denatures the proteins and 3) providing optimum pH (pH 2 to 3) for the action of
pepsin.
(HCl also kills microorganisms present in food).
9
Reactions of Protein Digestion
(In Stomach and Small Intestinal Lumen)
Dietary Proteins
In Stomach
Pepsin, HCl
Gastric Juice
Proteoses + Peptones (polypeptides and smaller polypeptides)
Trypsin
In Small Intestinal Lumen Chymotrypsin Pancreatic Juice
Elastase
Small Polypeptides + Peptides
Carboxypeptidases
Pancreatic Juice
In Small Intestinal Lumen Aminopeptidases
Dipeptidases
Intestinal Juice
Amino acids
Absorption of Amino Acids
Amino acids, the end products of protein digestion, are rapidly absorbed from the
intestine into the portal blood.
Amino acids are transported by a number of carriers many by secondary active transport
–Na+-dependent carriers similar to glucose transporter system.
Different Na+ -dependent carriers are:
- Neutral amino acid carrier
- Phenylalanine and methionine carrier
- Carrier specific for imino acids (proline and hydroxy proline)
There are also Na+-independent carriers specializing in the transport of
- Neutral and lipophilic amino acids (e.g. Phe, Leu)
- Cationic amino acids (e.g. Lys)
Clinical Significance
- Allergy to certain food proteins (milk, fish) is believed to result from absorption of
partially digested proteins.
- Defect in non-tropical sprue is located within the mucosal cells of the intestine and
permits the polypeptides (resulting from the peptic and tryptic digestion of gluten, the
principal protein of wheat) to be absorbed into the circulation and thus elicit the
production of antibodies.
- Defect in the intestinal amino acid transport systems are seen in Hartnup’s disease,
[defect in intestinal neutral amino acid (Trp) carrier], Iminoglycinuria, cystinuria etc.
10
- Acute pancreatitis (acute inflammation of pancreas), a life threatening disorder, is caused by
autodigestion of pancreas by its proteolytic enzymes. Autodigestion is due to unusual
conversion of proenzymes into active enzymes by trypsin.
Digestion and Absorption of Lipids
Contents:
–
–
–
–
–
Introduction
Digestion of fat
Digestion of other lipids
Absorption of lipids
Clinical significance
Introduction
– More than 90% of the dietary lipids are fats and oil (triacylglycerols). The rest is mainly
made up of cholesterol and phospholipids.
– The main site of digestion and absorption of lipids is the small intestinal lumen.
– Bile salts help both in digestion of fat and absorption of digested products of lipids.
– Heat of the stomach is important in liquidizing the dietary lipids.
Digestion of Fat (Triacylglycerols)
– Small intestinal lumen is the main site of digestion of fat.
– Digestion of fat involves hydrolysis of ester bonds, produces fatty acids, glycerol and
monoacyl glycerols (MAGs) and is catalyzed by lipases.
– Pancreatic lipase, present in the pancreas is the main enzyme for digestion of most of
the fat.
– Colipase, a protein secreted by pancreas, acts as cofactor for pancreatic lipase.
– There are also other lipases – lingual lipase, gastric lipase and intestinal lipase – but
their contribution is negligible.
– Bile salts, present in bile, help fat digestion by emulsifying fat.
Role of Bile Salts in Fat Digestion
– The bile salts present in the bile lower the surface tension and emulsify fat in the
intestine.
– Intestinal peristalsis also helps in this.
– Emulsification increases the surface area of the fat droplets enabling more enzyme
(lipase) molecules to act and thus speeding up digestion.
11
Reactions of Digestion of Fat (Triacylglycerol)1
Triacylglycerol (Fat)
Lipase
Pancreatic Juice
Colipase
Fatty Acid
Diacylglycerol (DAG)
Lipase
Colipase
Fatty Acid
Monoacylglycerol (MAG)
Lipase
Colipase
Fatty Acid
Glycerol
The major end products of the digestion of fat are –
– monoacylglycerols (MAGs),
– glycerol and
– fatty acids
Digestion of Other Lipids
– Pancreatic secretion also contains cholesterol esterase and phospholipase A2.
– Cholesterol esterase hydrolyzes cholesterol ester to cholesterol and fatty acid.
– Phospholipase A2 hydrolyzes phospholipids to form lysophospholipid and a fatty
acid.
Absorption of Digested Products of Lipids
– The water soluble products of lipid digestion – glycerol as well as small- and mediumchain fatty acids (chain length less than 12 carbons) are directly absorbed from the
intestinal lumen in to the portal vein and taken to the liver
Reference
12
1. Digestion of fat requires another enzyme also an isomerase, which isomerizes 2-MAG
into 1-MAG, as lipase cannot hydrolyze 2-MAG.
– The more water-insoluble products – monoacylglycerols, long-chain fatty acids,
cholesterol and lysophospholipids – are incorporated into bile salt micelles2 to form
mixed micelles.
– These mixed micelles fuse with the cell membrane of intestinal mucosal cells whereby
the products of lipid digestion are internalized into the mucosal cells3.
– Triacylglycerols are reconstituted in the intestinal mucosal cells and incorporated into
chylomicrons (a lipoprotein) along with apolipoproteins, cholesterol, phospholipids and
fat-soluble vitamins absorbed from the intestine.
– The chylomicrons are collected by the lymphatic vessels that lead to the blood stream by
the way of thoracic duct4.
– Normally Over 98% of the dietary lipid is absorbed.
.
Reference
2. – Bile salt and lecithin (a phospholipid) that are present in bile are amphipathic and hence
form micellar aggregation.
– The micelles are spherical particles with a hydrophilic exterior and hydrophobic interior
core.
3. – The bile salts are left behind which are mostly reabsorbed from the ileum and returned to
the liver to be excreted back to the bile (enterohepatic circulation).
4. – The chyle (milky fluid) from the intestinal mucosal cells loaded with chylomicron are
transported through the lymphatic lacteals into the thoracic duct and then emptied into
systemic circulation.
– The serum may appear milky after a high fat meal (post-prandial lipemia) due to the
presence of chylomicron in circulation. Normally the lipemia clears within a few hours
by the uptake of chylomicron by tissues.
13
Absorption of Digested Products of Lipids
Digested Products of Lipids
Water-insoluble
Monoacylglycerols
Long-chain fatty acids
Cholesterol
Water-soluble
Glycerol
Short- and Medium-chain fatty acids
Micelles
Fat-soluble vitamins
Mixed micelles
SMALL INTESTINAL LUMEN
Intestinal Epithelial Cell
Monoacylglycerols
Long-chain fatty acids
Cholesterol
Fat-soluble
vitamins
Triacylglycerol
Phospholipids
Apolipoproteins
Chylomicron
Chylomicron
LYMPHATIC VESSELS
Glycerol PORTAL BLOOD
Short- and Medium- chain fatty acids
Clinical Significance
Steatorrhea
- When daily excretion of fat in feces is more than 6g per day, the condition is called
steatorrhea.
- It may be due to defective digestion or defective absorption of fat.
- Defective digestion of fat may be due to absence of or deficiency of pancreatic lipase as in
chronic diseases of pancreas or surgical removal of pancreas.
- Defective absorption of fat occurs when bile salts do not enter the intestine as in biliary
obstruction (e.g. due to biliary stone)
- Defective absorption may also be due to malabsorptive diseases e.g. celiac disease, Sprue,
Chrohn’s disease, etc or surgical removal of large lengths of the intestine.
Chyluria and Chylothorax5
Reference
14
5. Chyluria is an abnormality in which patient excretes milky urine because of the presence of
an abnormal connection between the urinary tract and the lymphatic drainage system of the
intestine, a so-called chylous fistula. In a similar abnormality – chylothorax, there is an
abnormal connection between the pleural space and the lymphatic drainage of the small intestine
that results in the accumulation of milky pleural fluid.
15