Download 09Metabolism of dietary lipid

Lipid Metabolism
• Metabolism of dietary lipids.
• -Oxidation of fatty acids.
• Ketone bodies.
• Biosynthesis of fatty acids.
• Biosynthesis of triacylglycerols.
• Biosynthesis of cholesterol, steroids.
• Plasma lipoproteins.
Biochemistry of Lipids
• Classification.
1- Storage lipids.
2- Structural lipids in membranes.
3- Lipids as signals, cofactors and pigments.
Storage lipids
• Fatty acids are hydrocarbon derivatives.
- C4 to C36.
- Saturation.
- Nomenclature.
- Physical properties.
• Triacylglycerols.
- Simple vs. complex triglycerides.
- Function: provide stored energy and insulation.
• Waxes.
- Functions: serve as energy stores and water repellents.
Structural lipids in membranes
Types of membrane lipids:
1- Glycerophospholipids:
- Phosphatidic acid.
2- Sphingolipids:
- Sphingosine.
- Biological recognition.
- Degradation.
3- Sterols:
- Steroid nucleus.
- Functions.
Lipids as signals, cofactors and pigments
Phosphatidylinositols act as intracellular signals.
Eicosanoids carry messages to nearby cells.
- Prostaglandins.
- Thromboxanes.
- Leukotrienes.
Triacylglycerols
• Steroid hormones carry messages between tissues.
• Vitamins A and D are hormone precursors.
• Vitamins E and K are oxidation-reduction cofactors.
Lipid Classes
Glycerophospholipids
“Phospholipids”
SphingoLipids
Metabolism of dietary lipids and -oxidation of fatty
acids
Advantages of using fats as storage form of energy
- The
carbon atoms are more reduced than those of sugars 
oxidation of fats yields more energy.
-They are hydrophobic, unhydrated, no extra weight of hydration.
-They don’t increase osmolarity inside cells because they are not soluble.
Digestion, mobilization and transport of fats
cells can obtain fatty acid fuels from three sources:
1- fats consumed in the diet (60-150 gm/day , TG 90% , cholesterol)
2- fats stored in cells as lipid droplets (adipocytes)
3- fats synthesized in one organ to be exported to another. (excess
CHO is converted to fats in the liver to be exported to other cells)
* dietary fats are absorbed in the small
intestine
- dietary lipids are not digested to any extent in
the mouth or stomach in adults.
The rate of action of acid-stable lipase is very
slow in adults, because it is active only at neutral
pH.
In infants this enzyme may have a role.
In the duodenum : emulsification of the dietary
lipids occurs.
* Lipids are insoluble  hydrolysis occurs only at
the interfaces  emulsification increase surface
area of lipid droplets .
- this occurs by:
1- bile salts act as detergents.
bile salt = bile acid (steroid nucleus) + glycin or
taurine.
2- mechanical mixing due to peristalsis  Forming
of micelles
Hydrolysis of Choesteryl ester
Cholesteryl
esterase
Hydrolysis of Triglycerides
* Colipase enzyme secreted
by the pancreas to anchor
and stabilize the lipase at
the lipid- aqueous interface.
Hydrolysis of Phospholipids
(Lysolecithin)
Phospholipase A2 : secreted from
pancreas, removes the F.A from C2
* Absorption of lipids by intestinal mucosal cells
The primary products of dietary lipid degradation with the bile salts from mixed micelles.
Short and medium chain length F.A don’t need micelles formation to be absorbed (pass
directly)
hydrophilic
Hydrophobic
core
Brush membrane
Resynthesis of triacylglycerol and cholesteryl esters by the
intestinal mucosal cell
Resynthesis of triacylglycerol and cholesteryl esters by the intestinal
mucosal cell
long fatty acid fatty acyl synthetase (thiokinase)
fatty acyl CoA
-short and medium F.A are released into the portal circulation where they are carried by
serum albumin to the liver.
- 2-monoacylglycerol + 2 fatty acyl CoA acyltransferase triacylglycerol
- also phospholipids, cholesterol esters are resynthesized by a family of acyl
transferases.
* Secretion of lipids from intestinal mucosal cells
newly synthesized triacylglycerol and cholesterol esters are packed as oily droplets
surrounded by protein and phospholipid and unesterified cholesterol  increase
solubility called (chylomicrons) .
*lipoproteins : lipid-binding proteins found in the blood. Responsible for transporting of
cholesterol, cholesterol esters, phospholipid and triacylglycerols between organs.
* Apolipoprotein (free form without lipid) + lipids = lipoproteins
spherical structure with hydrophobic core and hydrophilic surface. These aggregates
have various densities (chylomicrons, very low density lipoprotein VLDL, LDL, HDL, VHDL
Chylomicrons
chylomicrons move from intestinal mucosa into the lymphatic system then enter
the blood then carried to muscle and adipose tissue mainly. And also to other
tissues (heart, lung and kidney) where the chylomicrons are degraded.
*The protein moieties of apoproteins are
recognized by receptors on cell surfaces.
* Degradation of chylomicrons
Triglycerides of chylomicrons are degraded
to free fatty acid and glycerol by
lipoprotein lipase that is activated by (apo
C-)..
•free fatty acids are oxidized for fuel or
resynthesized for storage.
* glycerol is converted to glycerol 3phosphate in the liver
* remaining of chylomicrons are taken by
the liver (that contains cholesterol,
cholesterol esters, phospholipids, proteins
and some T.G)
Chylomicrons
Bile salts are synthesized
from cholesterol in the liver
and stored in the bilary gland
and act as detergent
(amphipathic)
Formation of micelles increase
the surface of lipids exposed
to the enzymes which is water
soluble.
T.G lipase 2-monogycerol
+ 2 F.A
Cholesterol ester
cholesterol
* Use of dietary lipids by the tissues
T.G in chylomicrons are broken down mainly by skeletal muscles and adipose tissue. other
organ can utilize T.G like heart, kidney, liver and lung.
T.G in chylomicrons are degraded into free F.A and glycerol by lipoprotein lipase. This
enzyme is synthesized mainly by skeletal muscle and adipose tissue.
T.G
free F.A + glycerol
* Fate of fatty acids
-free fatty acid may directly enter the adipocyte or myocyte to be utilized or can be
transported with the blood to other cells to be utilized there. F.As are associated with
serum albumin until they are taken by other cells.
-F.As in skeletal muscles are oxidized to produce energy by -oxidastion.
-F.As in adipocyte are reesterified to produce T.G to be stored.
* Fate of glycerol
-glycerol that is released from T.G hydrolysis is taken by the liver to produce glycerol 3phosphate and enter glycolysis or gluconeogenesis.
* Fate of chylomicron remnants
- it contains cholesterol, cholesterol esters, phospholipids, proteins and little T.G.
- chylomicrons remnants are taken up by the liver where they are hydrolyzed to their
components and can be recycled.
Metabolism of glycerol
Oxidatio
n
T.G lipase fatty acids
+
glycerol
Glycerol
kinase
In liver
Glycerol 3phosphate
dehydrogenase
Triose phosphate
isomerase
Hormones trigger mobilization of stored TG.
Low level of glucose
trigger the mobilization of
triacylglycerols
That stored
in adipocyte
Epinephrine
Glucagon
Decrease blood glucose
increase epinephrine and increase
Glucagon
activation of lipase
increase hydrolysis of TG from
adipocytes
Can’t be
metabolized by
adipocytes
* Metabolism of dietary lipids
A) Limited processing of lipids in mouth and stomach.
B) Emulsification of dietary lipids in small intestine.
- bile salts
- mechanical mixing due to peristalsis
C) Enzymatic degradation of dietary lipids by pancreatic enzymes in the small
intestine.
- T.G degradation (pancreatic lipase)
- P.L degradation (phospholipase A2, lysophospholipase)
- cholesterol ester degradation (cholesterol esterase)
D) Absorption of lipids by intestinal mucosal cells.
- formation of mixed micelles, F.A + 2-monoacylglycerol + cholesterol + bile salts
E) Resynthesis of T.G and cholesterol esters by intestinal cells
- F.A thiokinase
fattyacyl CoA
- 2-monoacylglycerol + 2 fatty acyl acyl transferase
- cholesterol + fattyacyl CoA acyl transferase
T.G
cholesterol ester
F) Secretion of lipids from intestinal mucosal cell
chylomicrons transferred by exocytosis from intestinal cells into lymphatic system.
* Metabolism of T.G stored in adipocytes and -oxidation
•Mobilization of F.A from stored T.G in adipose tissue.
T.G
lipase
2-monoacylglycerol
glycerol + 3 F.A
* Fate of glycerol
- glycerol can’t be metabolized by adipocytes because of the lack of glycerol kinase.
So it released and transported to liver to be metabolized.
* Fate of free fatty acid
- free fatty acid from adipocytes transferred by blood bounded to albumin to
other organs to be used as fuels.
- brain, nervous tissues, erythrocytes and adrenal medulla cannot use plasma free
fatty acid as fuel, regardless of blood level of F.A.
* Different fates of T.G in liver and adipose tissue
- in adipose tissue : T.G is stored in the cytosol of the cell and it is ready for
mobilization when the body requires it.
- in liver : little T.G is stored, but most is exported and packaged with cholesterol
and cholesterol esters phospholipid
lipoproteins. Then secreted into the
blood.
The End
* Hormonal control of lipid digestion
* the hydrolytic enzymes that degrade lipids are secreted from pancreas and
this is controlled by hormones.
Cells from lower
duodenum and
jejunum produce
Cholecystokinin
Cause the gall bladder to
contract and to release its bile
salts also it decrease stomach
contraction (gastric motility)
Increase release of
bicarbonate solution to
increase pH to give
appropriate pH for
enzymatic digestion activity.
PANCREAS
GALL BLADDER
* Disorders of dietary lipid metabolism
1- lipid malabsorption
Inability of body to absorb the lipids and resulted in loss of lipids including fat soluble
vitamins A,D,E,K
and occurred at different conditions :
1- loss of bile salts.
2- loss of pancreatic enzymes.
3- deficiency of some hormones.
2- Congenital abeta lipoproteinemia
Deficiency of apo B-48 from intestinal cells
accumulation of T.G in intestinal mucosal cells.
decrease in synthesis of chylomicrons
3- Familial Lipoprotein Lipase deficiency (Type I hyperlipoproteinemia)
Resulted from deficiency of lipoprotein lipase and resulted in massive chylomicronemia
inability to use T.G from chylomicrons
4- Familial Type III hyperlipoproteinemia (familial dysbeta lipoproteimemia)
Defective in taking up the chylomicron remnants from plasma by the liver
accumulation of chylomicron remnants (cholesterol, cholesterol esters, … )
This due to deficiency of apolipoprotein E