This presentation demonstrates the digestion of dietary carbohydrates, lipids , and proteins in the human body

2. Professor Dr Ayman Barghash
Medical Biochemistry (MD)
Faculty of Medicine
Alexandria University

3. Digestion and
Absorption of Food

4. Lecture Instructions
Please:
1. Attend lecture at the exact time.
2. Never talk during the lecture.
3. Turn off your phone.
4. Lecture recording and photography are forbidden.
5. Questions are only allowed after the lecture or at
my office.

5. Office Hours
Day Time
Wednesday 21/3/2018 10 - 11 AM
Thursday 22/3/2018 10 - 11 AM

6. Lecture 1

7. Definition of Digestion
Brakdown
Lumen
of GIT
Amino acids
Segment of gastrointestinal tract (GIT)
 Hydrolytic enzymes
 Mechanical agitation
of food by GIT motility
Smaller food molecules
Epithelial cell
of GIT
Epithelial cell
of GIT
Epithelial cell
of GIT
Epithelial cell
of GIT
Epithelial cell
of GIT
Lumen of GIT
How does digestion
occur?
Epithelial cell
of GIT
Large food particle
What is meant by digestion?

8. Digestion
of Carbohydrates

9. Sources of Dietary Carbohydrates
Major
sources
Minor
sources
1. Starch
2. Sucrose
3. Lactose
1. Glucose
2. Fructose
3. Glycogen
4. Cellulose

10. Starch
Definition
 It is a plant polysaccharide.
 It is a polymer of glucose.
Food (dietary) source
 Bread
 Rice
 Pasta
 Potatoes

11. Starch grain
Structure of Starch
Amylopectin
Amylose
(outer coat)
(Branched,
(Linear helix,
(inner core)
~200,000 glucose units)
~100 - 4000 glucose units)

12. Chemical Structure of Amylose
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
4 1 α
α-Glucose
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
4 1 α
α-Glucose
H
H
H
O
OH
OH
H
H
CH2OH
O
H
H
H
O
OH
OH
H
H
CH2OH
O
H
H
H
O
OH
OH
H
H
CH2OH
O
1 1 1
4 4 4
α α α
Amylose
Free anomeric carbon
(reducing carbon)
α
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
α-Glucose
4 1
5
6
3 2
α 1,4 glucosidic linkages
Anomeric carbons are not free
(non-reducing carbons)
(non-reducing)
It is composed of: α Glucose units linked together by
α 1→ 4 glucosidic linkages

13. Chemical Structure of Amylopectin
OH
H
H
H
O
OH
OH
H
H
CH2OH
O
H
H
H
O
OH
OH
H
H
CH2
O
H
H
H
O
OH
OH
H
H
CH2OH
O
1 1 1
4 4 4
α α α
6
Main chain of amylopectin (similar to amylose)
Start of branching
H
OH
H
H
O
OH
OH
H
H
CH2OH
OH
4 1 α
H
HO
H
H
O
OH
OH
H
H
CH2OH
O H
4 1 α
α-Glucose
α 1,6-branch point
H
HO
H
H
O
OH
OH
H
H
CH2OH
4 1 α
O
H
H
H
O
OH
OH
H
H
CH2OH
O
H
H
H
O
OH
OH
H
H
CH2
O
H
H
H
O
OH
OH
H
H
CH2OH
O
1 1 1
4 4 4
α α α
6
α 1,4 glucosidic
bond
H
OH
H
H
O
OH
OH
H
H
CH2OH
O
4 1 α
H
H
H
O
OH
OH
H
H
CH2OH
4 1 α
O
H
H
H
O
OH
OH
H
H
CH2OH
O
H
H
H
O
OH
OH
H
H
CH2
O
H
H
H
O
OH
OH
H
H
CH2OH
O
1 1 1
4 4 4
α α α
6

14. Reducing and Non-reducing Ends of Starch (and
Glycogen)
Reducing ends
Non-reducing
ends
Amylose of starch
(linear chain)
1
1
1
1
1
1
1 1
1
4
4
4
4
4 4
4 4
4
(formed by
free anomeric
carbons)
Amylopectin of
starch & glycogen
(branched chain)

15. Glycogen
Definition
 It is a animal polysaccharide.
 It is a polymer of glucose.
Food (dietary) source
 Liver
 Muscles

16. Amylopectin
Glycogen
 Highly branched
 Has high MW
 Composed of up to 1,000,000
glucose units
Structure of Glycogen
 Less branched than glycogen
 Has smaller MW than glycogen
 Composed of about 200.000
glucose units
The structure of glycogen is similar to that of amylo-
pectin of starch with some differences

17. Chemical Structure of Glycogen (cont.)
1
1
1
1
1 1
4
4 4
4
4
4
6
α (1→4) glucosidic linkages
α (1→6) branch point
Branch
Main chain

18. Digestion of Dietary Carbohydrates
I. Digestion in the mouth
 It is catalyzed by salivary α-amylase.
 The enzyme breaks down starch into dextrins.
Site of secretion of salivary amylase
Salivary glands.
Optimum pH of salivary amylase
6.8

19. Action of Salivary α-Amylase
.
α 1→ 4 glucosidic linkage
α 1→ 6 glucosidic linkage
D-glucose units
α-Dextrin
Glycogen or amylopectin of starch (glucose polymer)
Salivary α-amylase
It randomly hydrolyzes the α 1→4 glucosidic
linkages within the glucose polymer resulting in
dextrins.

20. Action of Salivary and Pancreatic α-Amylases
(cont.)
α 1-6 branch point
(α 1-6 glucosidic linkage)
Terminal α 1-4
glucosidic linkage
Terminal α 1-4
glucosidic linkage
α 1-4 glucosidic linkage
next to branching point
 They randomly hydrolyze the α 1→4 glucosidic
linkages within the glucose polymer (starch or
glycogen).
 They do not hydrolyze:
Starch or glycogen

21. Digestion of Dietary Carbohydrates (cont.)
II. Digestion in the intestine
It is catalyzed by:
A. Pancreatic α-amylase
B. Intestinal oligo1→6 glucosidase (α-dextrinase =
isomaltase)
C. Intestinal disaccharidases

22. Digestion of Dietary Carbohydrates (cont.)
A. Pancreatic α-amylase
 Site of secretion
Exocrine pancreas
 Optimum pH
~ 8

23. Action of Pancreatic α-Amylase on Glucose
Polymers (starch, glycogen or dextrins)
α-Dextrin (glucose polymer)
D-glucose units
α 1- 4 glucosidic linkage
α 1- 6 glucosidic linkage
Pancreatic α-amylase
α-Limit dextrin
Maltotriose Maltose
 It randomly hydrolyzes the α 1→4 glucosidic
linkages within the glucose polymer (starch,
glycogen or dextrins).

24. Digestion of Dietary Carbohydrates (cont.)
B. Intestinal oligo1→6 glucosidase (α-dextrinase =
isomaltase)
 Location
At the brush border of the intestinal mucosal
cells.

25. Borders of Intestinal Mucosal Cell (Enterocyte)
.
Segment
of small
intestine
Brush
border
of
intestinal
mucosal
cell
Intestinal
mucosal
cell
Intestinal
oligo1→6
glucosidase
Lumen of small intestine
Contraluminal (basal)
side of enterocyte
Lateral side
of enterocyte
Luminal surface
of enterocyte
(brush border)

26. Action of Intestinal Oligo1→6-glucosidase
D-glucose units
α 1→ 4 glucosidic linkage
α 1→ 6 glucosidic linkage (branch point)
α-Limit dextrin (branched)
Glucose
Intestinal
oligo1→6 glucosidase
 It hydrolyzes the α 1→6 branch point of the α-limit
dextrin.
α-Limit dextrin (unbranched)

27. Dietary Disaccharides
 They include:
1. Sucrose
2. Maltose
3. Lactose

28. Sucrose
Definition
It is a disaccharide
Food (dietary) source
 Sugar cane
 Beet

29. Chemical Structure of Sucrose
α-Glucose
β-Fructose
α 1→2 or β 2→1
glycosidic linkage
β
1
2
1
α
OH
H H
H
O
OH
OH
H
H
CH2OH
OH
H
H
O
OH
HO
H
CH2OH
HOCH2
OH
H H
H
O
O
OH
OH
H
H
CH2OH
H
H
O
OH
HO
H
CH2OH
HOCH2
OH
β
1
2
1
α
Sucrose
Free anomeric
carbons
No free anomeric
carbons
(non-reducing)

30. Maltose
Definition
It is a disaccharide.
Food (dietary) source
 Malt.
 End product of digestion of starch and glycogen.

31. Chemical Structure of Maltose
4
α-Glucose
α-Glucose
α 1→4 glucosidic linkage
α 1
1 α
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
H H
H
O
OH
OH
OH
H
H
CH2OH
OH
Maltose
4
α 1
1 α
Free anomeric
carbon
(reduing sugar)
H
O
H H
H
O
OH
OH
OH
H
H
CH2OH
H
H
O
OH
OH
H
H
CH2OH
HO

32. Lactose
Definition
It is a disaccharide.
Food (dietary) source
 Milk.

33. Chemical Structure of Lactose
β
β-Galactose
H
H
O
OH
OH
H
H
CH2OH
HO
H
OH H
H
O
OH
OH
OH
H
H
CH2OH
H
OH
α
α-Glucose
1 1
β 1→4 glycosidic linkage
β α
1
1
Lactose
Free anomeric
carbon
(reduing sugar)
4
4
O
H
H
O
OH
OH
OH
H
H
CH2OH
H
H
O
OH
OH
H
H
CH2OH
HO
H
H

34. Digestion of Dietary Disaccharides by
Intestinal Disaccharidases
Sucrose
Glucose Galactose
Glucose
Fructose
Sucrase Maltase Lactase
Lactose
Maltose

35. Cellulose
Definition
It is a plant polysaccharide that makes up the cell
wall of plants.

36. Chemical Structure of Cellulose
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
H
HO
H
H
O
OH
OH
H
H
CH2OH
OH
β-Glucose β-Glucose β-Glucose
1 1
1 β
β β
Cellulose
β-1→4 glucosidic linkages between
β-glucose monomers
1 1
1 β
β β 4
4 4
H
H
H
O
OH
OH
H
H
CH2OH
H
H
H
O
OH
OH
H
H
CH2OH
H
H
H
O
OH
OH
H
H
CH2OH
O
O O

37. N.B.
 Cellulose is a part of the dietary fiber and is not
digested in the human body due to absence of
cellulase (β- glucosidase) which breaks down the
β 1→4 glucosidic linkages of cellulose, so it
passes unchanged through the intestine into the
feces. However it is a beneficial component of
human diet.

38. Health Effects of Dietary Fibers
Absorb large volumes of H2O
from the gut and become bulky
Reduction of
postprandial blood
glucose
3. An increase in the bulk
of intestinal contents
Stimulation of peristalsis
Shortening of the time
of intestinal evacuation
1. Sensation of fullness
2. Delay of gastric empting
Dietary fibers

39. 1. Reduction of water
absorption from large
intestine & softening
of stool
2. Decreased intestinal
absorption and increases fecal
loss of dietary fat & cholesterol
a. Constipation
b. Hemorrhoids
c. Diverticulosis
a. Decreased plasma total
cholesterol
b. Decreased plasma LDL-C
Decreased risk of CVD
3. Decreased time of gut exposure to carcinogens
Decreased risk of gut cancer
Shortening of the time of intestinal evacuation
Reduced

40. Lactose Intolerance
Definition
It means inability to digest lactose due to lactase
deficiency.
Causes of lactase deficiency
1. Genetic defect due to mutation in the gene coding
for lactase.
2. Acquired defect due to:
a. Injury of intestinal mucosa by disease or drugs.
b. Physiological decline in lactase activity with age.

41. Segment of
large
intestine
Lactase deficiency in small intestine
Osmotic diarrhea
Biochemical Basis of Lactose Intolerance
Passage of undigested lactose to large intestine
Undigested lactose
H2O
H2O
2 & 3 Carbon fragments
e.g. lactic acid & ethanol
(osmotically active)
Bacterial fermentation
H2O
H2O
Release of large
volumes of CO2 and H2
Flatulence
(abdominal distension)
& degradation into
Lumen of large intestine
Cell of
large
intestine
Cell of
large
intestine
Lumen of large intestine
H O
H O
Reinforces osmotic diarrhea
(osmotically active) & (composed of 12 Carbons)

42. Lactose intolerance (cont.)
Diagnosis
1. Lactose tolerance test
- A concentrated lactose solution is given orally.
- The blood glucose level is measured two hours
after the intake of lactose solution.
- Absence of a rise in the blood glucose level
indicates lactose intolerance.

43. Lactose intolerance (cont.)
Diagnosis
2. Hydrogen breath test
- A concentrated lactose solution is given orally.
- The amount of hydrogen in the expired air is
measured.
- A rise in the amount of hydrogen in the expired air
indicates lactose intolerance (normally very little
hydrogen is detectable in the exhaled air).

44. Lactose intolerance (cont.)
Treatment
1. Avoid or reduce the intake of milk and dairy
products.
2. Give lactose-free formula for infants and children.
3. Use lactase containing-pills before ingestion of
milk and dairy products.

45. Absorption of
Carbohydrates

46. Definition of Absorption
 Absorption means transport of the products of
food digestion from the lumen of gastrointestinal
(GIT) to the epithelial cells of the GIT and from
there to the blood stream.

47. Definition of Absorption
Amino acids
Portal blood
Absorption
Epithelial
cell of
intestine
Products of
digestion
Lumen of
intestine
Segment of small intestine

48. Absorption of Digested Carbohydrates
 The end products of carbohydrate digestion:
Monosaccharides e.g. glucose, galactose and
fructose.
 Main site of absorption
Duodenum and upper jejunum.
 Amount absorbed
One g glucose can be absorbed for each Kg of
body weight per hour.

49. Absorption of Digested Carbohydrates (cont.)
Maximal rate of glucose absorption
120 g/hour.
Glucose absorption is insulin-independent i.e.
insulin is not required for the uptake of glucose
by the intestinal cells.

50. Types of transport systems with regard to the
direction of movement and whether one or more
unique molecules are moved
Membrane
Lipid bilayer
Uniport antiport
Symport
Co-transport
Transport
protein
Transport
protein
Transport
protein

51. Absorption of Monosaccharides
Glucose
K+
Portal
Blood
ADP +Pi + E
Intestinal
lumen
Na+
Na+
SGLT1
Na+/K+
ATPase
pump
GLUT2
GLUT5
Fructose
Intestinal
mucosal cell
Brush
(lumenal)
border or
apical side
Basolateral
side
Galactose
Glucose
Galactose
Na+ K+
ATP
Na+
Secondary active co-
transport (symport)
Pentoses
Fructose
Pentoses
Facilitated diffusion
Liver

52. Fate of Monosaccharides in Liver
Liver
Glucose
Fructose Galactose
Galactose
Fructose
Glucose
Portal vein

53. Fate of Glucose in Liver
Liver
Acetyl
CoA
Systemic circulation
Lipids
To maintain the blood
glucose level during fasting
Glycogen
CO2 + H2O
+ Energy
Oxidative
decarboxylation
Glycogenesis
Pyruvate
Glucose

54. Digestion and Absorption
of Lipids

55. Sources of Dietary Lipids
 Oils.
 Butter.
 Liver.
 Brain.
 Egg yolk.

56. Types of Dietary Lipids
 Triacylglycerol (TAG).
 Phospholipids (PL).
 Cholesterol (C) & cholesterol ester (CE).
 Free fatty acids (FFAs).
 Fat-soluble vitamins (A,D,K,E).
10%
90%

57. Structure of Triacylglycerol (TAG)
CH2 OH
HO CH
CH2 OH
1
2
3
CH2 O
O CH
CH2 O
1
2
3
Glycerol backbone
C R
O
Acyl group
Acyl group
C R
O
R C
O
Acyl group
Ester bond
Ester bond
Ester bond
Triacylglycerol

58. Structure of Phospholipids
R-C -
Acyl group
O
- C-R
Acyl group
O
Nitrogenous
base
CH2-O
O-CH
CH2-O
1
3
2
- P- O -
Phosphate group
O
O-
(unsaturated)
Glycerol backbone
(Amphipathic)
Phosphoryl base
Hydrophilic (polar)
Diacylglycerol
Hydrophobic (non-polar)

59. Structure of Free Cholesterol
.
21 22
20
23
27
26
25
24
HO
3
Free Cholesterol is an amphipatic molecule
Hydrophobic (non-polar) hydrocarbon tail
Hydrophilic
(polar) head
Cholesterol
Steroid ring
is an alcohol

60. Structure of Cholesterol Ester
R - C -
O
Ester bond
21 22
20
23
27
26
25
24
O
3
Acyl group
of fatty acid
Cholesterol ester is a completely hydrophobic molecule
Hydrophobic
Hydrophobic
21 22
20
23
27
26
25
24
HO
3
Cholesterol (alcohol)
Cholesterol ester

61. I. Digestion of Triacylglycerols (TAG)
A. In the mouth
No digestion of fat occurs.
B. In the stomach
Gastric lipase
Site of secretion
Cells of the gastric mucosa.
Optimum pH
~ 5.

62. 1. Digestion of Triacylglycerols (TAG)
Action of gastric lipase
 It is specific for hydrolysis of ester bonds of TAG
containing short chain fatty acids such as TAG of
milk.
 This enzyme plays an important role in lipid
digestion in infants because:
1. TAGs of milk- which is the main food of infants-
are rich in short chain FAs.

63. I. Digestion of Triacylglycerols (TAG) (cont.)
2. pH in the stomach of infants is about 5 which is
optimum for the action of gastric lipase of
infants.
 In contrast, the action of gastric lipase is
insignificant in adults because the pH in their
stomach is around 2 which is unsuitable for the
action of the enzyme.

64. 1. Digestion of Triacylglycerols (TAG) (cont.)
C. In the small intestine
Pancreatic lipase
 It is the main enzyme of TAG digestion.
 Optimum pH
7.

65. I. Digestion of Triacylglycerols (TAG) (cont.)
 Requirements for the action of pancreatic lipase
 Prior emulsification of lipids which is carried out
by;
a. Bile salts.
b. Mechanical agitation due to peristalsis.
c. Phospholipids.
 Colipase.
 It is a protein needed as a cofactor for activity of
pancreatic lipase.

66. Gut Motility, Bile Salts, and Phospholipids are
Emulsifying Agents
Bile salts
Large lipid particle
(smaller surface area)
Smaller lipid particles
with larger surface
area, so more enzyme
molecules can get to
work
Emulsification
Phospholipids
Gut motility

67. Bile Salts, and Phospholipids are Emulsifying
Agents
Large lipid particle
(small surface area)
Emulsification
Small lipid particles (with larger surface
area) that cannot re-associate
Bile salts
Phospholipids

68. Action of Pancreatic Lipase
Intestinal lumen
Segment of small intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
(Aqueous environment)
Large
lipid particle
Surface of
lipid particle
facing the
aqueous
environment
Pancreatic lipase
(water soluble)
Pancreatic lipase
(water soluble)

69. Action of Pancreatic Lipase on
Triacylglycerols (TAG)
2 H2O 2RCOOH
Triacylglycerol
(Amphipathic)
CH2-OH
R2-C O-CH
CH2-OH
O
1(α)
2(β)
3(α)
CH2-O C-R1
R2-C O-CH
CH2-O C-R3
O
O
O
1(α)
2(β)
3(ὰ)
(Amphipathic)
Free Fatty acid
2(β)-Monoacylglycerol
(Hydrophobic)
Absorbed
as such
into
72%
Pancreatic lipase
pH 7
Absorbed
within
micelles into
Intestinal cell
Intestinal cell
Pancreatic
isomerase
28%
OH
H
OH
H
2RCOO
-

70. as
1- monoacylglycerol (28%)
CH2-O C-R1
HO-CH
CH2-OH
O
1
2
3
Passes to
Portal blood
Passes by
diffusion into
Intestinal cell
Intestinal cell
Absorbed
within
micelles into
Pancreatic lipase
(in intestinal lumen)
22% 6%
Absorbed as
such within
micelles into
Intestinal cell
Glycerol
Pancreatic isomerase
Passes to
Liver
H OH
FFA

71. End Products of Digestion of TAG
TAG
6%
2- monoacylglycerol
72%
1- monoacylglycerol
Glycerol
22%
(Major end product)
CH2-OH
R2-C O-CH
CH2-OH
O
1
2
3
CH2-O C-R1
HO-CH
CH2-OH
O
1
2
3
CH2-OH
HO-CH
CH2-OH
1
2
3
R-COOH
+ FFAs

72. II. Digestion of Phospholipids by
Phospholipases
CH2-O
O-CH
CH2-O
R-C -
Acyl group
O
- C-R
Acyl group
O
- P- O
Phosphate group
O
- Base
1
3
2
O-
Phospholipase A1
Phospholipase A2
Phospholipase D
Phospholipase C
(unsaturated)

73. N.B.
• Phospholipase A2 (PLA2) is of pancreatic origin,
while phospholipases A1, C, and D (PLA1, PLC,
PLD) are of intestinal origin.

74. II. Steps of Digestion of Phospholipids
H2O R-COOH
Phospholipid Lysophosphatide
Pancreatic
Phospholipase A2
1
2
3
CH2-O C-R1
R2-C O-CH
CH2-O P- O-Base
O
O
O
O
1
2
3
CH2-O C-R1
HO-CH
CH2-O P- O-Base
O
O
O
Free Fatty acid
(Amphipathic)
(Amphipathic)
(Amphipathic)
R-COOH
H2O
Phospholipase A1
(lysophospholipase)
Absorbed as such
within micelles
OH H
OH
H
Bile salts
+
Pancreatic pro-
phospholipase A2
Trypsin
+
R-COO
-
(Major fate)
Further
degradation

75. Digestion of Phospholipids (cont.)
.
O
CH2-OH
HO-CH
CH2 – O – P – O – Base
O
Excreted
as such in stool
undergoes
further
degradation
Glyceryl phosphoryl base

76. Degradation of Glyceryl Phosphoryl Base
.
Glycerol Glycerol Phosphate
Phospholipase C Phospholipase D
CH2-OH
HO-CH
CH2 – O – P – O – Base
O
O
Phosphoryl base base
Glyceryl phosphoryl base

77. Digestion of Cholesterol Ester
R - C
O
O
Cholesterol ester
Free cholesterol
H2O
Cholesterol ester hydrolase
(esterase)
(Hydrophobic)
(Amphipathic)
(Amphipathic)
Acyl group
of FA
R-C- OH
O
Free fatty acid
Ester bond
OH
H
HO
R-C- O
-
O

78. Summary of Digestion of Lipids
. Gut lumen
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Gut
Mucosal
Cell
Glycerol
Short & medium
chain FAs
Digestion
(stomach &
Intestine)
Gut
Mucosal
Cell
Segment
of GIT

79. Absorption of Lipids (cont.)
. Intestinal lumen
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Intestinal
Mucosal
Cell
Glycerol
Short & medium
chain FAs
Digestion
(stomach &
Intestine)
Intestinal
Mucosal
Cell
Diffusion
Glycerol
Short & medium
chain FAs
Portal
vein
Liver
(FFAs are
carried by
plasma
albumin)
Mixed
micelle
Bile
salts

80. End Products of Digestion of Fat
Intestinal lumen
Amino acids
Segment of small intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Epithelial cell
of Intestine
Intestinal lumen
Long chain FA
(Amphipathic)
Lysophosphatide
(amphipathic)
Fat-soluble vitamins
(hydrophobic)
2-monoacylglycerol
(Amphipathic)
Free cholesterol
(amphipathic)
2-monoacylglycerol
(Amphipathic)
Bile salts
(Amphipathic) Lysophosphatide
(amphipathic)
Long chain FFA
(Amphipathic)
Free cholesterol
(amphipathic)
Fat-soluble
vitamin
(Hydrophobic)
Bile Salts Form Mixed Micelles in Intestinal Lumen
Mixed Micelle

81. Absorption of Lipids (cont.)
. Intestinal lumen
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Intestinal
Mucosal
Cell
Glycerol
Short & medium
chain FAs
Digestion
(stomach &
Intestine)
Intestinal
Mucosal
Cell
Diffusion
Glycerol
Short & medium
chain FAs
Portal
vein
Liver
(FFAs are
carried by
plasma
albumin)
Mixed
micelle
Bile
salts
Mixed
micelle
Portal
vein
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Bile
salts
Resynthesis
 Triacylglycerol
 Cholesterol ester
 Phospholipids
 Free cholesterol
 Fat-soluble vitamins
Enterohepatic
circulation
of bile salts

82. Re-synthesis of TAG inside Intestinal Cells
Acyl
Acyl
Acyl OH
P
OH
1-Monoacylglycerol (6%)
2-Monoacylglycerol (72%)
Glycerol 3-phosphate
(Active glycerol)
Triacylglycerol
Monoacyl-
glycerol
pathway
Dihydroxy
acetone
phosphate
Glycolysis
Absorbed
micelles
Acyl CoA
OH
OH
OH
Glycerol
Intestinal
lipase
FFA
(22%)
Triacylglycerol
Acyl CoA
synthetase
CoSH
ATP + Mg2+
Glycerol
kinase
ATP +
Mg2+
2 CoASH
Acyl
OH
OH
1
2
3
Acyl
OH
OH
1
2
3
Phosphatidic acid
pathway
3 CoASH Pi
Intestinal cell
2 Acyl CoA
Glucose
DH
3 Acyl CoA

83. Re-synthesis of Phospholipids and Cholesterol
Ester Inside intestinal Cells
Free cholesterol
Phospholipid
Lysophosphatide
Cholesterol ester
Acyl CoA
Intestinal cell
CoASH

84. Absorption of Lipids (cont.)
. Intestinal lumen
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Intestinal
Mucosal
Cell
Short & medium
chain FAs
Glycerol
Digestion
(stomach &
Intestine)
Intestinal
Mucosal
Cell
Diffusion
Short & medium
chain FAs
Glycerol
Portal
vein
Liver
(FFAs are
carried by
plasma
albumin)
Mixed
micelle
Bile
salts
Mixed
micelle
Portal
vein
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Bile
salts
Resynthesis
 Triacylglycerol
 Cholesterol ester
 Phospholipids
 free cholesterol
 Fat-soluble vitamins
Enterohepatic
circulation
of bile salts
Nascent
Chylomicron
Form
Apo-A &apo-B48

85. Nascent Chylomicron
A
B-100
Spherical particle
Free cholesterol
(Amphipathic)
Phospholipids
(Amphipathic)
Phospholipids
Outer coat
Inner core
 Hydrophobic lipids
TAG & CE
 Apolipoproteins (apo)
e.g. Apo A and
apo B-48
 Amphipathic lipids
Free Cholesterol

86. Absorption of Lipids (cont.)
. Intestinal lumen
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Triacylglycerol
Free cholesterol
Cholesterol ester
Phospholipids
Fat-soluble vitamins
Intestinal
Mucosal
Cell
Short & medium
chain FAs
Glycerol
Digestion
(stomach &
Intestine)
Intestinal
Mucosal
Cell
Diffusion
Short & medium
chain FAs
Glycerol
Portal
vein
Liver
(FFAs are
carried by
plasma
albumin)
Mixed
micelle
Bile
salts
Mixed
micelle
Portal
vein
Long chain FAs
2-monoacylglycerol
Free cholesterol
Lysophosphatides
Fat-soluble vitamins
Bile
salts
Resynthesis
 Triacylglycerol
 Cholesterol ester
 Phospholipids
 free cholesterol
 Fat-soluble vitamins
Enterohepatic
circulation
of bile salts
Nascent
chylomicron
Form
Apo-A &apo-B48
Intestinal
lymphatics
Thoracic
duct
Systemic
circulation
Milky
appearance
of plasma
Release of
LPL
Exocytosis
Maturation

87. Maturation of Chylomicrons
BLOOD
Apo B-48 Apo CII
Apo E
TAG>PL, CE
C,
Mature
chylomicron
Apo A
HDL
Apo B-48
Apo
A
TAG>PL, CE
C,
Nascent
chylomicron
Small
Intestine
Apo B-48
Apo
A
TAG>PL, CE
C,
From HDL
Apo CII ApoE
+
Nascent
chylomicron
Maturation

88. 120
Milky Appearance of Plasma after a Fatty Meal
Transparent Cloudy (opaque, turbid)

89. Role of Lipoprotein Lipase (LPL) in the
Metabolism of Chylomicrons
Endothelial cells
LPL
Blood capillary of
extrahepatic tissues
Glycerol
Mature
Chylomicron
TAG
(90%)
CE
C, PL
Apo
CII
Apo
B 48
Apo
E
FFA
Capillary wall
+
LPL: Lipoprotein lipase

90. Catabolism of TAG of Chylomicrons by
Plasma LPL
3 H2O 3 R - COOH
Triacylglycerol
CH2-O C-R1
R2-C O-CH
CH2-O C-R3
O
O
O
1
2
3
CH2-OH
HO-CH
CH2-OH
1
2
3
Glycerol
Lipoprotein Lipase (LPL)
Free Fatty Acids
OH
H
OH
OH
H
H

91. N.B.
 LPL is called “plasma clearing factor” because it
clears the cloudiness (turbidity) of the plasma
caused by the entry of chylomicrons into the
blood stream following the ingestion of a fatty
meal. LPL hydrolyzes TAG of chylomicrons.
 Insulin induces (enhances the synthesis) of LPL
and heparin increases its activity.

92. Fate of Glycerol
Tissues containing active glycerol kinase
Liver
Active glycerol
(glycerol 3- phosphate)
Converted to
TAG
Cardiac & skeletal
muscles
Active glycerol
Oxidized to yield energy
Passes to
Oxidized to yield
energy
Converted to
glucose
Mainly to Partly to

93. Fate of Free Fatty Acids
Adipose tissues & lactating
mammary gland
Stored as TAG.
Cardiac & skeletal
muscles
Oxidized to yield energy
Bind to plasma
albumin & pass to

94. Digestion and Absorption of
Dietary Proteins

95. Sources of Dietary Proteins
A. Animal source
1. Meat.
2. Poultry.
3. Fish.
4. Milk.
5. Egg.
B. Plant source
1. Cereals.
2. Beans.

96. N.B.
- As a rule, proteins are generally too large to be
absorbed by the intestine, so they must be
hydrolyzed to smaller di- and tripeptides as well as
free amino acids before absorption.
- An exception to this rule is that newborns can
absorb maternal antibodies (IgA) taken up with
breast milk without degradation to amino acids.

97. Digestion of Proteins
 Proteins are digested by proteolytic enzymes
which are also called peptidases or proteases.
 Proteolytic enzymes digest proteins by breaking
down their peptide bonds by a hydrolytic reaction.

98. Peptide Bond
Dipeptide
Amino acid
Amino acid
H2O
H2N CH C OH
R1
O
H N CH COOH
R2
H
Peptide bond
N CH COOH
R2
H2N CH C
R1
O
H
Amino group
Carboxyl group

99. +
Inhibitory
peptide
Catalytic site Catalytic site
(exposed)
Gastrointestinal Zymogens (Proenzymes)
GIT Zymogen
Active enzyme
Inhibitory or
blocking peptide
E E
Properly folded
enzyme
(inactive enzyme)
(masked)
Activation

100. Proteolytic Enzymes (peptidases, proteases)
A. Gastric proteolytic enzymes
1. Pepsin.
2. Parachymosin.
B. Pancreatic proteolytic enzymes
1. Trypsin.
2. Chymotrypsin.
3. Elastase.
4. Carboxypeptisaes A and B.

101. Proteolytic Enzymes = Peptidases (cont.)
C. Intestinal proteolytic enzymes
1. Aminopeptidases.
2. Tripeptidase.
3. Dipeptidase.
4. Enterokinase (enteropeptidase).

102. Endo- and Exopeptidases
Exopeptidase
Aminopeptidase Carboxypeptidase
Endopeptidase
O R H O R H O R
H2N-CH-C N-CH-C N-CH-C N-CH-C N-CH-C N-CH-COOH
R H O R H O R H
Carboxy(C)-terminal
peptide bond
Amino (N)-terminal
peptide bond
Polypeptide chain
Internal peptide
bonds
Peptide bonds
(CO-NH)

103. I. Digestion of proteins in the mouth
Proteins are not digested in the mouth due to
absence of proteolytic enzymes.
II. Digestion of proteins in the stomach
1. Gastric HCl
- It is released from the parietal cells of the gastric
mucosa.
- It is too dilute to hydrolyze proteins.
Steps of Digestion of Proteins

104. Layers of the Stomach
Parietal cell
(secretes HCl)
Neuroendocrine
cell (secretes
histamine,
gastrin)
Chief cell
(secretes
pepsin)

105. II. Digestion of Proteins in the Stomach (cont.)
Action of gastric HCl
1. It denatures proteins making them more
susceptible to subsequent digestion by
proteases.
2. It activates pepsinogen to pepsin.
3. It makes pH of the stomach suitable for the action
of pepsin (pH=2).
4. It helps digestion of sucrose.
5. It kills some of the bacteria in the stomach.

106. +
Inhibitory
peptide
Catalytic site
Gastric HCl
Catalytic site
(exposed)
II. Digestion of Proteins in the Stomach (cont.)
Pepsinogen Pepsin
(active)
Autocatalysis
+
Inhibitory peptide
(44 amino acids)
Properly folded
enzyme
(inactive)
Optimum pH = 2
2. Pepsin
(secreted by chief cells
of the gastric mucosa)
(masked)

107. Action of Pepsin
O R H O R H O R
H2N-CH-C N- CH-C N-CH-C N- CH-C N- CH-C N- CH- COOH
R H O R H O R H
Pepsin
Aromatic
amino acid
e.g. Phe, Tyr
Polypeptide
chain
Amino
terminal peptide
bond
Carboxy
terminal peptide
bond
Any
amino acid
Internal
Peptide bond
Proteoses and peptones

108. II. Digestion of Proteins in the stomach (cont.)
3. Parachymosin
 It is a milk clotting enzyme present in infants.
 It is similar to rennin of calves.
 Optimum pH:
6-7.

109. Action of Parachymosin
Caseinogen
(of milk)
Parachymosin
Soluble casein
Calcium
(of milk)
Ca caseinate
(milk clot or cheese)

110. N.B.
 Clotting of milk prevents its rapid passage from
the stomach allowing digestive enzymes to act on
its components.

111. Steps of Digestion of Proteins
III. In the small intestine
A. Pancreatic proteolytic enzymes
 They include the following enzymes;
1. Trypsin
2. Chymotrypsin
3. Elastase
4. Carboxypeptidases (A & B)

112. III. Digestion of Proteins in the Small Intestine
A. Pancreatic Proteolytic Enzymes
 They are released as inactive zymogens that are
activated in the lumen of intestine by trypsin.
 Optimum pH: 7- 8.
 Each enzyme cleaves a specific peptide bond.
 They hydrolyze large polypeptides (produced by
the action of pepsin in the stomach) into oligo-
peptides and free amino acids.

113. Digestion of Proteins in the Small Intestine
by Pancreatic Proteolytic Enzymes
H O H
H
H
H
H2N – C – C – N – C – C – N – C – C – N – C – C – N – C – C – N – C – C – N – C – C – N – C - COOH
H
R R R R
H
H
H
H H
O
O
O
O H
H
H
H O
O R
R R
R
Basic AA
Arg
Lys
Aromatic AA
Phe
Tyr
Trp
Carboxypeptidase
(contains Zinc)
Ala
Gly
Ser
Small non-polar AA
Procarboxypeptidase
Chymotrypsin
Trypsin
Trypsinogen Chymotrypsinogen
Elastase
Prolastase
Enterokinase
(Enteropeptidase)
Segment
of small
intestine
Polypeptide chain
 All are released as zymogens and become activated by trypsin.
 All are secreted from pancreas
 Optimum pH for all = 7-8
 All are endopeptidases except carboxypeptidase.
Autocatalysis
Amino acid

114. N.B.
 Enterokinase is an example of enzyme that
activates other enzyme.

115. +
Active site
(blocked)
Blocking hexapeptide
(6 amino acids)
Active site
(exposed)
Activation of Trypsinogen to Trypsin by
Enteropeptidase and by Trypsin
Trypsinogen
(inactive)
Trypsin
(active)
Blocking
hexapeptide
(6 amino acids)
Enteropeptidase
(Enterokinase)
Autocatalysis
+
E E
Activation

116. N.B.
Enzymes that contain zinc include:
1. Alkaline phosphatase.
2. Carbonic anhydrase.
3. Lactate dehydrogenase (LDH).
4. Carboxypeptidase.

117. Aminopeptidase
 It is located on the brush border of intestinal
epithelial cells.
 Its optimum pH is 7-8.
 It is an exopeptidase.
 It hydrolyzes the amino-terminal peptide bond
releasing free amino acids.

118. Action of Aminopeptidase
COOH
H2N
Polypeptide chain
Amino
terminal peptide
bond
Carboxy
terminal peptide
bond
Aminopeptidase
COOH
H2N
Polypeptide chain
(shorter by one amino acid)
Free
amino acid

119. Net Result of Protein Digestion
40%
Amino acids
60%
Di- and tripeptides

120. N.B.
Proteins are large molecules and are antigenic i.e.
able to stimulate the immune system if they
reaches the blood (e.g. If taken intravenously).
Digestion of proteins to amino acids removes their
antigenicity.

121. N.B.
 If a protein is not digested completely and is
absorbed as a polypeptide immunologic
allergy in the form of urticaria,
bronchial asthma, and hay fever (allergic rhinitis).
response
+

122. Abnormalities in Protein Digestion
Pancreatitis and surgical removal of pancreas
(pancreatectomy)
 They result in a deficiency of pancreatic secretion
including pancreatic lipolytic and proteolytic
enzymes incomplete digestion and
absorption of dietary lipids and proteins
abnormal appearance of lipids in feces (called
steatorrhea) as well as appearance of undigested
proteins in feces.

123. Absorption of Proteins
Digestion
Intestinal
cell
Intestinal
lumen
Amino acids
1111
Segment of small intestine Portal Blood
Amino acids
Absorption of Amino Acids
Na +- linked
Secondary active transport
Protein
Lumen

124. Absorption of Peptides and Amino Acids
Intestinal cell
Portal blood
Segment of small intestine
Dipeptidase
Na
+
-linked
amino
acid
&
peptide
secondary
active
transport
Tripeptide
Amino
acid
Dipeptide
Intestinal
lumen
Na+- K+
ATPase
3Na+
2K+
ATP ADP + Pi + E
Intestinal cell
Intestinal cell
Lumen

125. N.B.
 Triprptidase is located in the cytoplasm of the
intestinal epithelial cells.
 Diprptidase is located in the cytoplasm and on
the brush border of the intestinal epithelial cells.

126. Hartnup's disease
 It is a genetic disease characterized by inability of
the renal tubular cells to reabsorb and inability of
intestinal mucosal cells to absorb neutral amino
acids (including tryptophan which is an essential
amino acid).
 Manifestation
1. Amino aciduria.
2. Pellagra-like manifestations due to deficiency of
tryptophan.

127. ‫السالم‬
‫عليكم‬
‫و‬
‫هللا‬ ‫رحمة‬
‫و‬
‫بركاته‬