lipid metabolism explained in detail (biochemistry)human nutrition covered

1. LIPOPROTEIN
METABOLISM AND
DISORDERS
NAME –ETIKA SAXENA
REg.NO -12106012
COURSE CODE –NUT109

2. Lipoprotein Metabolism
All the lipids contained in plasma, including fat, phosphalipids, cholesterol,
cholesterol ester and fatty acid, exist and transport in the form of lipoprotein
Structure
▶ Non-covalent assemblies
of lipids and proteins
▶ LP core
▶ Triglycerides
▶ Cholesterol esters
▶ LP surface
▶ Phospholipids
▶ Proteins
▶ cholesterol
Function as transport vehicles for
triacylglycerols and cholesterol in the blood

4. Lipids are Transported as Lipoproteins
⚫All lipids in plasma are transported in the
form of lipoproteins .
⚫Transport dietary lipids from intestine to liver
(exogenous) Chylomicrons
⚫Transport lipids from liver to peripheral tissues
(endogenous) VLDL(very low density lipoproteins)

6. Classification
Density (g/mL) Class
Diameter
(nm)
%
protein
%
cholesterol
%
phospholipid
%
triacylglycerol
& cholesterol
ester
>1.063cc HDL 5–15 33 30 29 4
1.019–1.063 LDL 18–28 25 50 21 8
1.006–1.019 IDL 25–50 18 29 22 31
0.95–1.006 VLDL 30–80 10 22 18 50
<0.95 Chylomicrons 100-1000 <2 8 7 84

7. Apolipoproteins
(apoproteins)
▶ They are the protein components of lipoproteins
▶Consisting:
▶ 60% of some lipoproteins (HDL)
▶ and 1% of some lipoproteins (chylomicrons)
▶ The major apoprotein of HDL is designated
A, and of LDL is apo-B which is also found in VLDL and
chylomicrons

8. Metabolism of Lipoproteins

9. Metabolism Of Chylomicron
FUNCTION :
transport exogenous TG (dietary fat) from the intestine to the
peripheral tissues; where TG is used as an energy source or stored in
adipose tissue
Step 1:
⚫ Nascent chylomicrons are formed in the intestinal mucosa and pass to
the blood stream
Nascent chylomicrons consists of :
⚫ rich in dietary TG + minimal amount of dietary cholesterol + apoB,
which is necessary for assembly of the chylomicron.
⚫ The lipid component is very high, thus, it is of least density.

10. Step 2:
After passage to blood, addition of apoC and apoE from HDL
leads to the formation of mature chylomicrons.
Step 3:
⚫ Capillary lipoprotein lipase (LPL), activated by apoC,
hydrolyzes TG present in chylomicrons into fatty
acids + glycerol + producing chylomicron remnant
(chylomicron containing less TG and more cholesterol+
apoE+ apoB) which are taken up by the liver
through endocytosis.

11. Step 4
1. Glycerol is phosphorylated in the liver by glycerol kinase
glycerol 3-phosphate which is used to synthesize more
VLDL.
2. Free fatty acids
for storage.
In muscle
enter the adipose tissue to produce TG
the fatty acids are oxidized to provide energy.
3. ApoC returns to HDL

12. 4. Chylomicron remnants attach to apoE receptors in the
liver and are endocytosed.
5.Dietary cholesterol delivered to the liver via chylomicron remnants
is used for bile acid synthesis.
6. Excess cholesterol is excreted in bile.

14. Metabolism of VLDL and
production of LDL
1- Synthesis of nascent VLDL
⚫ Nascent VLDL are synthesized in the liver.
⚫ They transport TG synthesized in the liver (endogenous fats) to peripheral tissues
to be available as energy source or for storage.
⚫ also contain some cholesterol (17%)
⚫ Its apoprotein is apoB-100.
2- Conversion to mature VLDL:
⚫ Nascent VLDL are released into the blood by the liver.
⚫ They receive apo-C11 , E and cholesterol esters from HDL in plasma, converting to
mature VLDL.

15. 3-Degradation by plasma lipoprotein lipase
(LPL):
⚫ In peripheral tissues, adipose tissue and muscles, VLDL/ TG are
hydrolyzed by lipoprotein lipase (LPL).
⚫ The LPL (activated by apoC of VLDL) hydrolyses TG/VLDL into fatty acids
+glycerol+ VLDL remnants (Intermediate-density lipoproteins (IDL);
containing less of TG and more of cholesterol).
⚫ A small part of VLDL remnant is taken up by the liver, by receptor-
mediated endocytosis.
⚫ The major fraction of VLDL remnant further loses TG, so as to be
converted to LDL.
⚫ This conversion of VLDL to IDL and then to LDL is referred to as:
lipoprotein cascade pathway.

17. Low density lipoproteins (LDL)
⚫ All LDL arise normally from VLDL metabolism.
⚫ Structure of LDL:
⚫ Apo-B100 is the only apolipoprotein in LDL particles.
⚫ LDL is a cholesterol-rich particle, because it has minimum TG

18. The function of LDL:
1- transport cholesterol from liver to peripheral tissues
2- regulate cholesterol synthesis.
3-LDL are important source of cholesterol to extrahepatic tissues.
4-. It is the major transport form of cholesterol/blood
5 The liver has a major role in controlling LDL cholesterol/ plasma
due to:
(1) Most of the LDL receptors are present in the liver;
(2) The liver synthesizes cholesterol.
(3) It removes cholesterol from lipoprotein remnants.
(4) It is the only organ that can excrete cholesterol through bile.

19. It is risk factor;
⚫High levels of LDL -cholesterol increase
the risk of atherosclerosis.

20. Fates of Free Cholesterol
Transported to the Cells by LDL:
 Incorporated into cell membranes.
 Metabolized to steroid hormones.
 Re-esterified and stored.
 excreted through liver.

22. ⚫ They are formed by the liver cells and intestinal mucosa.
⚫ These are the smallest and the most dense lipoprotein particles.
⚫ They contain large amount of proteins (50-60%) and very little
triglycerides, while the predominant lipid is phospholipid.

23. Function of HDL
⚫1- Removing free cholesterol from extra hepatic
tissues and esterifing it using plasma
enzyme called lecithin-cholesterol-acyl transferase
(LCAT). The apo A1 of HDL activates LCAT.
⚫ they transport cholesterol esters to the liver.
⚫ Hepatic lipase (similar to LPL) hydrolyses HDL and
cholesterol esters free Cholesterol, which
either:
Enters in the formation of lipoprotein.
Converted to bile acid.
Excreted into bile for removal from the body.

24. ⚫ HDL is Very safe.
⚫ The level of HDL in serum is inversely related to atherosclerosis and
myocardial infarction.
⚫ HDL is known as good cholesterol
⚫ 2- A major function of HDL is to act as a source for apo C and apo E that
are required in the metabolism of chylomicrons and VLDL.
⚫ 3- Transport phospholipids from liver to tissues.

26. DISORDERS OF LIPOPROTEIN
• Inherited disorders of lipoproteins are encountered in some
individuals resulting in primary hyper- or
hypolipoproteinemia
 genetic defects in lipoprotein metabolism and transport.
 acquired lipoprotein disorders are due to some other diseases
(e.g. diabetes mellitus, atherosclerosis hypothyroidism etc.),
resulting in abnormal lipoprotein

27. H YPER lipoproteinaemia

28. HYPO lipoproteinaemia
▶ Familial alpha-lipoprotein deficiency (Tangier disease):
• The plasma HDL particles are almost absent. Due to this, the
reverse transport of cholesterol is severely affected leading to
the accumulation of cholesteryl esters in tissues.
• An absence of apoprotein C-which activates lipoprotein lipase-
is also found. The plasma triacylglycerol levels are elevated.
The affected individuals are at an increased risk for
atherosclerosis

29. FATTY LIVER
• The normal conc. of lipid is 5%
• Lipids is stored excessively- Fatty liver- lmpaired synthesis
of lipoproteins–increased VLDLsynthesis
▶ Fatty liver refers to the deposition of excess triglycerides in the
liver cells.
• In fatty liver, droplets of triacylglycerols are found in the
entire cytoplasm of hepatic cells.
• Causes impairment in metabolic functions of liver.
• Fatty liver is associated with fibrotic changes & cirrhosis.

30. IMPAIRED SYNTHESIS OF LIPOPROTIENS
• The synthesis of very low density lipoproteins(VLDL) actively
takes place in liver.
• VLDL formation requires phospholipids & apoprotein B.
• Impaired lipoprotein synthesis may be due to:
• Defect in phospholipid synthesis.
• Ablock in apoprotein formation.
• Afailure in the formation/secretion of lipoprotein.
• Fatty liver due to impairment in phospholipid synthesis

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