TỔNG ÔN TẬP THI VÀO LỚP 10 MÔN TIẾNG ANH NĂM HỌC 2023 - 2024 CÓ ĐÁP ÁN (NGỮ Â...
Metabolism of cholesterol -
1.
2. • Cholesterol is the most decorated small molecule in
biology.
• Thirteen Nobel Prizes have been awarded to
scientists who devoted major parts of their careers
to cholesterol.
• Ever since it was first isolated from gallstones in
1784, almost exactly 200 years ago, cholesterol has
exerted a hypnotic fascination for scientists from
the most diverse domains of science and medicine.
3. Organic chemists
• Its complex four-ring structure.
Biochemists
• Synthesized from a simple two-carbon substrate, acetate,
through the action of at least 30 enzymes.
Physiologists and cell biologists
• Its essential function in membranes of animal cells.
Physicians
• Elevated levels of bl cholesterol accelerate the formation of
atherosclerotic plaques leading to heart attacks & strokes.
F a s c i n a t i o n w i t h c h o l e s t e r o l . . .
Thestudies of cholesterol therefore embrace almost all disciplines of modern Sciences.
4. Cholesterol
Cholesterol is
the major
sterol in
animal
tissues.
No vegetable
oil contains
any
cholesterol.
Only a little
portion of the
body
cholesterol is
derived from
diet.
The bulk of it
is synthesized
in the body.
5. It has the ring called
cyclopentanoperhydrophenanthrene (CPPP)
as a parent structure.
OH
A B
C D
9. Biosynthesis of Cholesterol
About 1 gm of cholesterol is synthesized per day in
adults.
Almost all tissues of the body participate in the
cholesterol synthesis.
The largest contribution is made by……
LIVER (50%),
INTESTINE (15%),
SKIN,
ADRENAL CORTEX,
REPRODUCTIVE TISSUES.
10. The enzymes involved in the synthesis are found
in the CYTOSOL and MICROSOMAL fractions of
the cells.
Acetyl CoA provides the carbon atoms in the
cholesterol.
The reducing equivalents are supplied by NADPH
while ATP provides energy.
11. For production of 1 mole of cholesterol
18 moles of Acetyl CoA
36 moles of ATP
16 moles of NADPH
are required.
12. Formation of HMG CoA
Formation of Mevalonate (6C)
Production of Isoprenoid units (5C)
Synthesis of Squalene
Conversion of …..
Squalene to Cholesterol (27C)
Steps of the Cholesterol Synthesis
17. Regulation of Synthesis
HMG-CoA reductase is the rate limiting enzyme
in cholesterol biosynthesis.
The following are the different kinds of
metabolic control:
Feedback Regulation
Hormonal Regulation
Nutritional Regulation
19. Competitive inhibitor drugs of HMG-CoA reductase:
Pravastatin
Lovastatin
Mevastatin
Simvastatin
Fluvastatin
These are the structural analogues of intermediates
in the conversion of HMG-CoA to mevalonate
20.
21. Degradation of Cholesterol
Cholesterol undergo degradative reactions in
humans with conversion of cholesterol to
physiologically important products like,
Bile acids
& Bile Salts
Steroid
Hormones
Vitamin-D
22. Formation of Bile acids
The primary bile acids are
Cholic acid
Chenodeoxycholic acid
synthesized in the liver from cholesterol by
multistep pathways
24. The primary bile acids are conjugate with
glycine and taurine to form
Glycocholicacid
Taurocholic acid
Glycochenodeoxycholic acid
Taurochenodeoxycholic acid
25. The conjugated bile salts are synthesized in liver and
accumulated in the gall bladder.
From there they are secreted into the small intestine
where they are serve as a emulsifying agents for
digestion and absorption of fat.
26. A large portion of the bile salts are reabsorbed and
returned to the liver through portal vein.
Thus bile acids are recycled and reused several times
in a day.
This is known as Enterohepatic circulation.
The fecal excretion of bile salts is the only route for the
excretion of cholesterol from the body.
27.
28. Bile salts and phospholipids
are responsible for keeping the
cholesterol in bile in the soluble
state.
Due to their deficiency leads to
the accumulation of cholesterol
crystals in the gall bladder.
This condition is known as
cholelithiasis.
29. Patients with this condition are responds to the
administration of the bile acid chenodeoxycholic
acid known as CHENODIOL.
Surgical removal of gall bladder is the only
remedy.
30. Synthesis of Steroid Hormones
Cholesterol is the precursor for the synthesis of all the
five classes of steroid hormones like;
Glucocorticoid
Mineralocorticoids
Progesterones
Androgens
Estrogens
31. Synthesis of Vitamin D
7-dehydrocholesterol an intermediate of the
biosynthetic pathway of cholesterol, is
converted into cholecalciferol by ultra violet
rays in the skin.
32. Transport of Cholesterol
Cholesterol is present in the plasma lipoproteins in two
forms:
1. 70 to 75% are esterified form with long chain fatty
acid
2. 25 to 30% are free form this may exchange with
different form of lipoproteins.
36. Role of LCAT
HDL and the enzyme LCAT are the responsible for
the transport and elimination of cholesterol from
the body.
LCAT is a plasma enzyme synthesized in liver.
It catalyzed the transfer of the fatty acid from the
2nd position of the Phosphatidyl Choline (Lecithin)
to the hydroxyl group of the cholesterol.
38. Plasma Cholesterol
In healthy individuals, the normal cholesterol level is about 150
to 200 mg/dl.
The women have relatively less cholesterol which is attributed to
the hormones.
39. Plasma cholesterol is associated with the different forms of
lipoprotein fractions like:
HDL (40 to 60 mg/dl)
LDL (less than130 mg/dl)
VLDL (1/5th of TGL)
41. Major Sources of Liver Cholesterol and its
Utilization
CHOLESTEROL POOL
(1000mg)
Liver
Dietary
Cholesterol
(500mg/day)
Synthesis of
Cholesterol in
Liver
(500mg/day)
Cholesterol from extra
hepatic tissues
(Variable)
Bile acids and
Bile salts
(250mg/day)
Cholesterol lost
in bile
(500mg/day)
Lipoproteins
(variable)
43. It is also associated with
CHD
ARTHEROSCLEROSIS
44. Control of Hypercholesterolemia
Consumption of PUFA
Dietary Cholesterol
Dietary fibre
Avoid high Carbohydrate
Impact life style
Moderate alcohol consumption
Uses of drugs
45. HypoCholesterolemia
Seen in the following conditions:
Hyperthyroidism
Pernicious Anemia
Malabsorption syndrome
Hemolytic Jaundice