5 Metabolism of Lipids

8/6/2019 5 Metabolism of Lipids

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Metabolism of lipids.



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.



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.



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).



� 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



� Most bile

acids are

conjugated

with

glycine or

taurine.



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).



Triacylglycerol (TG) degradation.

Pancreatic lipase preferentially

removes the FA at carbons 1 and 3.



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.



� 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.



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.



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



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.



Cholesteryl ester (CE) degradation.



Phospholipid degradation.



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



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.



Chylomicron

composition.� Chylomicrons

contain 2% protein,

7% phospholipids,8% cholesterol or

its esters, and over

80%

triglycerides.The main

transported lipid

exogenous TG.



� They are released by

exocytosis from intestinal

mucosal cells into the

intestinal lecteals.

� From the thoracic lymphaticduct, the chylomicrons enter

the bloodstream.



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.



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.



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).



Lipoproteins of bloodplasma.



� 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.



� This is solved by associating nonpolar lipids

(triglycerol and cholesteryl esters) withamphipathic lipids (phospholipids and

cholesterol) and proteins to make water-

miscible lipoproteins.



Structure of

a typical

lipoproteinparticle.



� 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.



� 4 major groups of

lipoproteins have beenidentified that are important

physiologically and inclinical diagnosis.



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.



Composition

of theplasma

lipoproteins.



� Triacylglycerol is the

predominant lipid in

chylomicrons and VLDL,

whereas cholesterol andphospholipid are the

predominant lipids in LDL

and HDL, respectively.



� 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.



.

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



� 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).



Structure of

a typical

lipoproteinparticle.



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.



� 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



Metabolism

of

chylomicrons

� C M=chylomicron, TG=triacylglycerol,

C =cholesterol, CE =cholesterol esters



Metabolism of VLDL and LDL.



Metabolism of HDL.

� P C =phosphatidylcholine, P C AT=Phoshpatidylcholine

cholesterol transferase



Role of oxidazed lipoproteins in plaque

formation in arterial wall.

5 Metabolism of Lipids

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