metabolism of lipids

1. Metabolism of lipids.

2. Digestion of lipids.
•
An adult ingests about 60 to 150g of
lipids per day (90% of which are
Triacylglycerols (TG)).
• The human saliva contains no fat-
splitting enzymes.
• Therefore in the oral cavity, fats are
not digested.
• In adult humans, fats pass through
the stomach also essentially
unchanged, since lipase, contained
in a small amount in the gastric
juice of adult humans is not active.

3. 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.

4. Gastric lipase is active in infants
• The gastric digestion of fats takes
place mainly in children,
especially infants.
• The gastric pH in infants is
about 5, (optimal pH for gastric
lipase is 5,5-7,5).
• Fats of milk can be hydrolysed by
gastric lipase (milk is emultion).

5. • 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.
H3C
H3C CH–CH2–CH2–COOH
CH3
Cholanic acid

6. • Most bile
acids are
conjugated
with
glycine or
taurine.

7. 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.
2) Bile acid salts activate pancreatic
lipase.
3) Bile acid salts take part in the
absorption of fats in the intestine
(they form micelles with fat
digestion).

8. Triacylglycerol (TG) degradation.
Pancreatic lipase preferentially
removes the FA at carbons 1 and 3.

9. Absorption of
lipids contained in
a mixed micelle.
• In the intestinal
lumen, long-chained
fatty acids and 2-
monoglycerides are
formed (under the
influence of lipase),
and they are
combined in
micelles.

10. • 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 acids
and 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.

11. 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
(2:0); propionic acid (3:0); butyric acid (4:0);
capric acid (10:0).) and glycerol owing to their
easy solubility in water, are readily absorbed
in the intestine and are supplied to the
portal vein blood to be delivered to the
liver, 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.

12. TG (exogenous)
emulsification
TG (emulsion)
hydrolysis
DG
2-MG
FFA
glycerol
bile acid salts and short-chain FFA
glycerol TG
DG
MG
FFA
Lungs
Adipose
tissue
formation of
transport form
thoracic
lymphatic
duct
chylomicrons
A
Babsorption resynthesis
H2O CO2
blood
stream
portal vein
lipase
Bile acid salts
+ bile acid
salts
micelles
Pancreas
Liver
Gallbladder

13. Digestion of phospholipids and cholesterol
esters
• As for digestion and absorption of
alimentary phosphoglycerides
and cholesterol esters,
practically all the above listed
stages are the same except
specific hydrolytic enzymes
(phospholipases A1, A2, C, D)
and cholesterol esterase
(cholesterol, FFA) respectively.

14. Cholesteryl ester (CE) degradation.

15. Phospholipid degradation.

16. TG (exogenous)
emulsification
TG (emulsion)
hydrolysis
DG
2-MG
FFA
glycerol
bile acid salts and short-chain FFA
glycerol TG
DG
MG
FFA
Lungs
Adipose
tissue
formation of
transport form
thoracic
lymphatic
duct
chylomicrons
A
Babsorption resynthesis
H2O CO2
blood
stream
portal vein
lipase
Bile acid salts
+ bile acid
salts
micelles
Pancreas
Liver
Gallbladder

17. Chylomicron formation.
• Triglycerides and phospholipids synthesized in
the epithelial cells of the intestine, as well as
cholesterol (possibly, partially esterified) combine
with a little of protein to form chylomicrons.

18. Chylomicron
composition.
• Chylomicrons
contain 2% protein,
7% phospholipids,
8% cholesterol or
its esters, and over
80% triglycerides.
The main
transported lipid –
exogenous TG.

19. • They are released by
exocytosis from intestinal
mucosal cells into the
intestinal lecteals.
• From the thoracic lymphatic
duct, the chylomicrons enter
the bloodstream.

20. Alimentary hyperlipemia.
• Already within 1-2 hours after intake of a lipid-
rich diet, the alimentary hyperlipemia is
observed in the organism.
• This is a transient physiological state,
characterized primarily by an increased
concentration of triglycerides in the blood and by
the occurrence of chylomicrons in it.
• The alimentary hyperlipemia passes its
maximum 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 normal
level, and chylomicrons are no more observed
in the blood.

21. 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.

22. Possible causes of
steatorrhea.
1) diseases of liver and
gallbladder (inability to
synthesize and secrete
bile).
2) Diseases of pancreas
(inability to secrete
pancreatic juice).
3) Defective intestinal
mucosal cells (inability
to absorb).

23. Lipoproteins of blood
plasma.

24. • Fat absorbed from the diet and lipids
synthesized 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 transport
them in an aqueous environment – the
blood plasma.

25. • This is solved by associating nonpolar lipids
(triglycerol and cholesteryl esters) with
amphipathic lipids (phospholipids and
cholesterol) and proteins to make water-
miscible lipoproteins.

26. Structure of
a typical
lipoprotein
particle.

27. • 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 phospholipid and
cholesterol molecules.
• These are oriented so that their polar
groups face outward to the aqueous
medium, as in the cell membrane.

28. • 4 major groups of
lipoproteins have been
identified that are important
physiologically and in
clinical diagnosis.

29. These are
1) chylomicrons, derived from intestinal
absorption of triacylglycerol;
2) very low density lipoproteins (VLDL, or
pre-β-lipoproteins), derived from the
liver for the export of triacylglycerol;
3) low-density lipoproteins (LDL, or β-
lipoproteins), representing a final stage
in the catabolism of VLDL;
4) high-density lipoproteins (HDL, or α-
lipoproteins), involved in VLDL and
chylomicron metabolism and also in
cholesterol transport.

30. Composition
of the
plasma
lipoproteins.

31. • Triacylglycerol is the
predominant lipid in
chylomicrons and VLDL,
whereas cholesterol and
phospholipid are the
predominant lipids in LDL
and HDL, respectively.

32. • In addition to the use of
techniques depending
on their density (by
ultracentrifuga-tion),
lipoproteins may be
separated according to
their electrophoretic
properties into α-,β-
and pre-β-lipoproteins
and may be identified
more accurately by
means of
immunoelectrophoresis.

33. .
Lipoproteins Electrophoreti
c fraction
Place of
synthesis
The main
transported lipid
Chylomicrons
1-2%protein;
90-1000nm
Origin Intestine Exogenous triacyl-
glycerols (from the
diet)
VLDL 7-
10%protein
30-90nm
Pre-β-
lipoproteins
Liver (intestine) Endogenous triacyl-
glycerols
(synthesized within
the organism)
LDL 21% protein
20-25nm
β-lipoproteins Blood (from
VLDL)
Cholesterol (to the
tissues)
HDL 33-57%
protein
10-20 nm
α-lipoproteins Liver (intestine) Cholesterol (from
the tissues to the
liver and
phospholipids)
Albumin-FFA
90% protein
Albumin Blood FFA

34. • 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).

35. Structure of
a typical
lipoprotein
particle.

36. Functions of apolipoproteins.
• Apolipoproteins not only give
1) water-solubility to lipids, but they are
necessary for
2) the secretion of lipoproteins by the cells
of the liver and intestine. They are also
necessary for
3) the processes of lipoprotein interaction
with receptors on the surface of the cells
(apo-B100, apo-E).
4) Also several apolipoproteins activate the
enzymes, participating in lipoprotein
metabolism.

37. 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.

38. • In healthy men on an empty stomach blood plasma
contains only HDL, LDL and VLDL. In healthy men there
is a parallel between cholesterol concentration in plasma
and cholesterol amount, included in LDL. The analogous
parallel exists between triacylglycerol concentration in
plasma and their concentration in VLDL. These
conclusions 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

39. Metabolism
of
chylomicron
s
• CM=chylomicron, TG=triacylglycerol,
C=cholesterol, CE=cholesterol esters

40. Metabolism of VLDL and LDL.

41. Metabolism of HDL.
• PC=phosphatidylcholine, PCAT=Phoshpatidylcholine
cholesterol transferase

42. Role of oxidazed lipoproteins in plaque
formation in arterial wall.