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Metabolism of lipids.
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Digestion of lipids.� An adult ingests about 60 to 150g of
lipids per day (90% of which areTriacylglycerols (TG)).
� The human saliva contains no fat-splitting enzymes.
� Therefore in the oral cavity, fats arenot digested.
� In adult humans, fats pass through
the stomach also essentiallyunchanged, since lipase, containedin a small amount
in the gastric juice of adult humans is not active.
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Gastric lipase is not active in adults
� The optimal pH for the gastric
lipase lies within the interval of 5,5-7,5.
� In adults the gastric juice pH is
about 1,5 (enzyme is not active).� In addition, lipase can actively
hydrolyze only pre-emulsified
fats.� In the stomach, there are no
conditions for the appropriate
emulsification of fats.
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Gastric lipase is active in infants
� The gastric digestion of fats takesplace mainly in children,
especially infants.
� The gastric pH in infants isabout 5, (optimal pH for gastric
lipase is 5,5-7,5).
� Fats of milk can be hydrolysed by
gastric lipase (milk is emultion).
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� In adults the splitting of dietary fats occurs
mostly in the upper segments of the small
intestine.� The most potent fat emulsifiers are bile acid
salts (supplied to the duodenum in the bile).
� Bile acids are the main end products of
cholesterol metabolism and derivatives of
cholanic acid.
3C3C C ±C 2 ±C 2 ±COO
C 3
Cholanic acid
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� Most bile
acids are
conjugated
with
glycine or
taurine.
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The significance of bile acid salts for
digestion of lipids :
1) The bile acid salts not only facilitate
emulsification, but also stabilize the
formed emulsion.
) Bile acid salts activate pancreatic
lipase.
) Bile acid salts take part in theabsorption of fats in the intestine
(they form micelles with fat
digestion).
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Triacylglycerol (TG) degradation.
Pancreatic lipase preferentially
removes the FA at carbons 1 and 3.
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Absorption of
lipids contained ina mixed micelle.
� In the intestinal
lumen, long-chainedfatty acids and -
monoglycerides are
formed (under the
influence of lipase),and they are
combined in
micelles.
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� Micelles are clusters of amphipathic lipids
(hydrophobic groups are inside; hydrophilic are
outside).� They are soluble in aqueous solution. These
micelles have hydrophobic core (fatty acids,
monoglycerides, etc.). It becomes enclosed
within a hydrophilic shell composed of bile acidsand phospholipids.
� In size, the micelles are smaller by a factor of
100 than the most finely dispersed fat
droplets.
� Short and medium chain-length fatty acids do not
require the assistance of micelles for absorption
by the intestinal mucosa.
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Differences in short and long-chain fatty acid
absorbtion.
� The short chain fatty acids (with the number of carbon atoms less than 10. Acetic acid( :0); propionic acid ( :0); butyric acid (4:0);capric acid (10:0).) and glycerol owing to their
easy solubility in water, are readily absorbedin the intestine and are supplied to theportal vein blood to be delivered to theliver , escaping ay conversion in the
intestinal wall.� In the intestinal wall from long-chain fatty
acids fats are synthesized again specific of the given organism and structurally distinct
from the alimentary fat.
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TG (exogenous)
emulsification
TG (emulsion)
hydrolysis
DG
2-MG
FFA
glycerol
bile acid salts and short-chain FFA
glycerol TG
DGMGFFA
Lungs
Adipose
tissue
formation of
transport form
thoraciclymphatic
duct
chylomicrons
A
Babsorption resynthesis
H
blood
stream
portal vein
lipase
Bile acid salts
+ bile acidsalts
micelles
Pancreas
Liver
Gallbladder
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Digestion of phospholipids and cholesterol
esters
� As for digestion and absorption of alimentary phosphoglyceridesand cholesterol esters,
practically all the above listedstages are the same exceptspecific hydrolytic enzymes
(phospholipases A1, A2, C, D)and cholesterol esterase(cholesterol, FFA) respectively.
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Cholesteryl ester (CE) degradation.
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Phospholipid degradation.
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TG (exogenous)
emulsification
TG (emulsion)
hydrolysis
DG
2-MG
FFA
glycerol
bile acid salts and short-chain FFA
glycerol TG
DGMGFFA
Lungs
Adipose
tissue
formation of
transport form
thoraciclymphatic
duct
chylomicrons
A
Babsorption resynthesis
H CO2
blood
stream
portal vein
lipase
Bile acid salts
+ bile acidsalts
micelles
Pancreas
Liver
Gallbladder
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Chylomicron formation.
� Triglycerides and phospholipids synthesized inthe epithelial cells of the intestine, as well ascholesterol (possibly, partially esterified) combinewith a little of protein to form chylomicrons.
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Chylomicron
composition.� Chylomicrons
contain 2% protein,
7% phospholipids,8% cholesterol or
its esters, and over
80%
triglycerides.The main
transported lipid
exogenous TG.
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� They are released by
exocytosis from intestinal
mucosal cells into the
intestinal lecteals.
� From the thoracic lymphaticduct, the chylomicrons enter
the bloodstream.
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Alimentary hyperlipemia.� Already within 1-2 hours after intake of a lipid-
rich diet, the alimentary hyperlipemia isobserved in the organism.
� This is a transient physiological state,characterized primarily by an increased
concentration of triglycerides in the blood and bythe occurrence of chylomicrons in it.
� The alimentary hyperlipemia passes itsmaximum within 4-6 hours after the intake of
fat-rich food.� In 10-12 hours after the intake of diet, the
triglyceride content comes back to the normallevel, and chylomicrons are no more observed
in the blood.
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Lipid malabsorbtion.
� Lipid malabsorbtion(resulting in
increased lipid (including the fat-
soluble vitamins A, D, E and K,and essential FA) in the feces
(that is steatorrhea) can be
caused by a number of
conditions.
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Possible causes of
steatorrhea.1) diseases of liver and
gallbladder (inability to
synthesize and secretebile).
2) Diseases of pancreas
(inability to secrete
pancreatic juice).) Defective intestinal
mucosal cells (inability
to absorb).
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Lipoproteins of bloodplasma.
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� Fat absorbed from the diet and lipidssynthesized by the liver and adipose
tissue must be transported between
the various tissues and organs for utilization and storage.
� Since lipids are insoluble in water, the
problem arises of how to transportthem in an aqueous environment the
blood plasma.
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� This is solved by associating nonpolar lipids
(triglycerol and cholesteryl esters) withamphipathic lipids (phospholipids and
cholesterol) and proteins to make water-
miscible lipoproteins.
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Structure of
a typical
lipoproteinparticle.
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� A typical lipoprotein such as
chylomicron or VLDL consists of a
lipid core of mainly nonpolar
triacylglycerols and cholesteryl esters
surrounded by a single surface layer of
amphipathic phosphoriented so that
their polar groups olipid and
cholesterol molecules.
� These are face outward to the aqueous
medium, as in the cell membrane.
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� 4 major groups of
lipoproteins have beenidentified that are important
physiologically and inclinical diagnosis.
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These are
1) chylomicrons, derived from intestinal
absorption of triacylglycerol;2) very low density lipoproteins (VLDL, or
pre- F-lipoproteins), derived from the liver
for the export of triacylglycerol;3) low-density lipoproteins (LDL, or F-
lipoproteins), representing a final stagein the catabolism of VLDL;
4) high-density lipoproteins (HDL, or E-lipoproteins), involved in VLDL andchylomicron metabolism and also incholesterol transport.
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Composition
of theplasma
lipoproteins.
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� Triacylglycerol is the
predominant lipid in
chylomicrons and VLDL,
whereas cholesterol andphospholipid are the
predominant lipids in LDL
and HDL, respectively.
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� In addition to the use of techniques dependingon their density (byultracentrifuga-tion),lipoproteins may beseparated according to
their electrophoreticproperties into E-, F-and pre- F-lipoproteinsand may be identifiedmore accurately by
means of immunoelectrophoresis.
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.
Lipoproteins Electrophoreti
c fraction
Place of
synthesis
The main
transported lipid
Chylomicrons
1-2%protein;90-1000nm
Origin Intestine Exogenous triacyl-
glycerols (from thediet)
VLDL 7-
10%protein
30-90nm
Pre--
lipoproteins
Liver (intestine) Endogenous triacyl-
glycerols
(synthesized withinthe organism)
LDL 21% protein
20-25nm
-lipoproteins Blood (from
VLDL)
Cholesterol (to the
tissues)
HDL 33-57%protein
10-20 nm
-lipoproteins Liver (intestine) Cholesterol (from thetissues to the liver
and phospholipids)
Albumin-FFA
90% protein
Albumin Blood FFA
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� The protein moiety of a lipoprotein is
known as an apolipoprotein or apoprotein,
constituting nearly 60% of some HDL and
as little as 1% of chylomicrons.
� Some apolipoproteins are integral (apo-
B) and can not be removed, where as
others are free to transfer to other lipoproteins (apo-C)( periferal).
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Structure of
a typical
lipoproteinparticle.
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The main types of apolipoproteins.
Apolipoprotein
Lipoprotein Known functions
A Chylomicrons, HDL Coenzyme of LCAT(A-1). Activator of
lecithin: cholesterol a acyltransferase .
B Chylomicrons, VLDL,
IDL, LDL
Secretion of chylomicrons (B-48);
secretion of VLDL; binding of LDL
with receptors (B-100); (ligand ror
LDL receptor).
C HDL, VLDL,
IDL,chylomicrons(from
HDL)
Coenzyme of lipoproteid lipase (C-2).
D HDL, VLDL, IDL,
chylomicrons (from
HDL)
Binding of IDL and remaining
particles with receptors.
E HDL Transfer of cholesterol esters.
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� In healthy men on an empty stomach blood plasma
contains only HDL, LDL and VLDL. In healthy men thereis a parallel between cholesterol concentration in plasmaand cholesterol amount, included in LDL. The analogousparallel exists between triacylglycerol concentration inplasma and their concentration in VLDL. Theseconclusions are right for the majority of hyperlipidemia
cases.� There is no apo-B in HDL.
� There is no apo-A in VLDL.
� Apo-A apo-B apo-B LDL
� Apo-B chylomicrons apo-C VLDL apo-A
� Apo-C apo-E apo-C HDL� Apo-E apo-D
� apo-E
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Metabolism
of
chylomicrons
� C M=chylomicron, TG=triacylglycerol,
C =cholesterol, CE =cholesterol esters
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Metabolism of VLDL and LDL.
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Metabolism of HDL.
� P C =phosphatidylcholine, P C AT=Phoshpatidylcholine
cholesterol transferase