The slides deal with the cholesterol structure,its metabolism and clinical significance

1. Presented by
Melbia shiny
First MDS
Oral medicine & radiology

2.  Light yellow crystalline solid
 Soluble in chloroform, & fat solvents
 Distributed in brain ,nerves, muscle,adipose
tissue ,skin ,blood, liver,& spleen.
 Absent in plant.

3.  has cyclopentano perhydrophenanthrene ring
,A,B,C,D rings are present.
 Has 27 carbon atoms.
 One hydroxyl group on third carbon atom
 Double bond between 5&6 C atoms
 8 C side chain.

5. 1. Cholesterol is precursor for synthesis of
vitamin D & bile acids .
2. Cell membrane- it has modulating effect on
fluid state of membrane.
3. Nerve conduction –it is used to insulate
nerve fibers.
4. Fatty acids transported to liver as
cholesterol esters for oxidation.

6. 5.Steroid hormones - glucocorticods
,androgene, estrogen are synthesized from
cholestrol.
6.Essential ingredient in structure of
lipoprotein.

9.  Cholesterol is excreted through bile prior
esterification with PUFA
 Partly reabsorbed from intestine
 Unabsorbed portion is acted by intestinal
bacteria to form cholestanol & coprostanol
which is excreated as fecal sterols
 Another part is converted into bile acids
,excreted as bilesalts.

10.  Synthesis of bile acids

13. Synthesis of vitamin D
cholestrol
7 dehydrocholesterol
uv rays
cholecalciferol
in liver
25 cholecalciferol
in kidney(parathromone)
1,25 dehydrocholecalciferol(active vitD)

14.  Being lipid it is insoluble in water
 Cholestrol is complexed with protein to form
lipoprotein.
 Protein part is apolipoprotein
 LACT(lecithin cholesterol acyltransferase) is
responsible for transport & elimination of
cholesterol from body

15. 1. Chylomicrons
2. Very low density lipoprotein(VLDL)
3. Intermediate density lipoprotein(IDL)
4. Low density lipoprotein(LDL)
5. High density lipoprotein(HDL)
6. Free fatty acids

16.  Lipoprotein have polar periphery made of
proteins (apolipoprotein), phospholipids, &
cholestrol.
 Inner core consists of hydrophobic TAG &
phospholipids

17.  Chylomicrons – intestinal mucosal cells
 VLDL – in liver from glycerol & fatty acid
 LDL – from VLDL , rich in cholestrol
 HDL - intestinal cells
 Free fatty acids – from lipolysis of
triglycerides

18.  Chylomicrons
 lipoprotein lipase
 Storage in adipose tissues
 Remnants taken by liver
 VLDL
 Activates lipoproteinlipase taken by adipose
tissue & muscle
 Remanent is IDL , loses triglycerides, form
LDL
 Lipoprotein cascade pathway

20.  LDL
 LDL receptors- clathrin coated pits
 Receptor-LDL complex internalized by
endocytosis
 Vesicle fuse with lysosomes
 Lysosomal enzyme degrade to form free
cholesterol

22.  HDL
 Intestinal cells – release nascent HDL
(discoid)
 LACT catalyses esterification of free
cholesterol & transfer to HDL
 HDL also recieves free cholesterol from
peripheral tissues
 Apoprotein A promote LACT activity
 Enter liver & are degraded

24.  Chylomicrons- transport of dietary
triglycerides from intestine to adipose tissue
for storage.
 VLDL – transport of endogenous triglycerides
from liver to peripheral tissues for energy
 LDL - transport cholesterol from liver to
peripheral tissues
 HDL – transport of cholestrol from peripheral
tissue to liver (reverse cholesterol
transport.)

26.  Atherosclerosis:
 Deposition of LDL
esp oxidised LDL in the subintimal regions of
arteries is atherosclerosis . are taken by
macrophages or scavengers – a starting
event in atherosclerosis leading to
myocardial infarction.
 LDL cholestrol is deposited in tissues hence
called bad cholestrol.

27. The hallmark of atherosclerotic plaque are the
foam cells (LDL degraded by macrophages
get overloaded with cholesterol)
Progression of atherosclerosis
atherosclerotic plaque lead to narrowing
of vessel wall when proliferative changes
occur .fibrous proliferation is due to
liberation of growth factors by macrophages
& platelets

28.  Blood flow through narrow lumen is
turbulent, so clot is formed which occludes
major vessels.
 Thrombosis leads to ischemia & finally
infarction.
 Early stages it is reversible by lowering LDL
level
 As lesion progresses arterial change become
irreversible.

29.  Risk factor for atherosclerosis:
1)serum cholesterol level
Normal cholesterol level – below 180
mg/dl
Value above 240mg/dl need active treatment
2)LDL cholesterol
normal – under 130mg/dl
above 160mg/dl - risk

30. 3)HDL level
Is inversely related to myocardial infarction
is antiatherogenic.
above 65mg/dl protect heart disease
Level below 40mg/dl – risk of CAD
Total cholesterol : HDL cholesterol > 3.5 ,
dangerous
LDL : HDL > 2.5 also dangerous
4)Apoprotein level
apo B : apo A1 is more reliable
0.4 is good , 1.4 risk of CAD

31. 5)Lipoprotein lipase
inhibit fibrinolysis
> 30mg/dl increases risk
6)Smoking
nicotine cause lipolysis & increase acetyl
coA & cholesterol synthesis
also cause constriction of arteries

32. 7)Hypertension
systolic pressure > 160 – risk of CAD
8)Diabetic mellitus
absence of insulin activates lipase , so
production of acetyl coA & finally
cholesterol synthesis.
9)Serum triglyceride
normal level- 50-150 mg/dl

33. 10)Obesity & sedentary life
Prevention of atherosclerosis
1)Reduction of dietary cholesterol
egg yolk & meat high cholesterol
2)Vegetable oil & PUFA
PUFA- esterification of cholesterol
omega 3 fatty acid in fish oil decrease LDL

34. 3)Moderation in fat intake
20 – 25g of oil & 2-3 g of PUFA per day
4)Green leafy vegetable
high fiber content- more bowel
motility & reduced reabsorption of bile salts
Sitosterol(plant sterol) decrease cholesterol
absorption
5)Avoid sucrose & smoking

35. 6)Exercise
moderate – lower LDL & raise HDL
7)Hypolipidemic drugs
atarvostatin ,lovastatin & simvostatin
(HMGCoA reductase inhibitors)
Cholestyramine & colestipol (bile salt binding
drug) – promote synthesis of bile salts & LDL
uptake by liver
Clofibrate- increase activity of lipoprotein
lipase

36. 8)Antioxidants
 Decrease oxidation of LDL
 Vitamine E &C or beta carotene

37.  Increase in plasma cholesterol (> 200 mg/dl)
 Observed in :
 Diabetics mellitus
 Hypothyroidism ( myxedema )
 Obstructive jaundice
 Nephrotic syndrome

38.  Seen in
 Hyperthyroidsm
 Pernicious anaemia
 Malabsorption syndrome
 Hemolytic jaundice

39.  Inherited disorders of lipoproteins are
primary hyper / hypolipoproteinemias
 Secondary lipoprotein disorders are due to
some other diseases

40. Elevation in one or more lipoprotein
Frederickson classification:
Type I
 Lipoprotein lipase deficiency
 > chylomicrons
Type IIa/hyperbetalipoproteinemia
defect in LDL receptor
LDL elevated

41. Type IIb
 LDL & VLDL elevated
 Due to overproduction of apo B
Type III/broad beta disease
 > IDL
Type IV
 > VLD
Type V
Chylomicrons & VLDL are elevated

42. Familial hypobetalipoproteinemia
 Impaired synthesis of apoprotein B
Abetalipoproteinemia
 Defect in synthesis of apo B
 Total absence of beta lipoprotein
 Less absorption of fat & fat soluble vitamins
Familial alpha lipoprotein
deficiency(tangier disease)
 HDL is absent

43.  Xanthomas-deposition of lipids in
subcutaneous tissues
 Xanthelesma- lipids deposited in periorbital
skin & contain cholesterol
 Corneal arcus – deposits of lipids in cornea
 xanthomatosis - deposition of lipids in liver
, spleen, & flat bone in skull
Fatty liver- Triglyceride synthesis &
accumulation
Impaired lipoprotein synthesis