This document discusses cholesterol synthesis, transport, and excretion. It describes how cholesterol is synthesized from acetyl-CoA in 5 steps: 1) mevalonate synthesis from acetyl-CoA, 2) conversion of mevalonate to isoprene units, 3) condensation of 6 isoprene units to form squalene, 4) conversion of squalene to lanosterol, and 5) formation of cholesterol from lanosterol. Cholesterol is transported in the blood plasma via lipoproteins and is excreted from the body in bile as cholesterol or bile acids which are synthesized from cholesterol in the liver.

1. CHOLESTROL SYNTHESIS,TRANSPORT AND
EXCRETION

2. BIOMEDICAL IMPORTANCE OF CHOLESTROL
• Cholesterol is a waxy, fat-like substance that's found in
all the cells in our body.
• Our body needs some cholesterol to make hormones,
vitamin D, and substances that help us in digestion of
foods.
• It is an essential structural component of membranes
in cell structure.
• It is synthesized in many tissues from acetyl-CoA and is
the precursor of all other steroids in the body such as
corticosteroids, sex hormones, bile acids, and vitamin
D.

3. BIOMEDICAL IMPORTANCE OF CHOLESTROL
• It is eliminated from the body either
unchanged or after conversion to bile acids.

4. Structure of Cholestrol
• 4 Non-Aromatic Rings
• 1 Carbon Double bond
• 1 Side Chain
• 1 Hydroxyl Group

5. Acetyl-CoA Is the Source of All Carbon Atoms in
Cholesterol
The biosynthesis of cholesterol may be divided into
five steps:
1. Synthesis of mevalonate occurs from acetyl-CoA.
2. Isoprenoid units are formed from mevalonate by
loss of CO2.
3. Six isoprenoid units condense to form squalene.
4. Squalene cyclizes to give rise to the parent
steroid, lanosterol.
5. Cholesterol is formed from lanosterol.

8. Stage 1 Biosynthesis of Mevalonate
• The first stage in cholesterol biosynthesis leads to the intermediate
mevalonate.
• Two molecules of acetyl-CoA condense to form acetoacetyl-CoA,
which condenses with a third molecule of acetyl-CoA to yield the
six-carbon compound -hydroxymethylglutaryl-CoA (HMG-CoA).
• Initially, two molecules of acetyl-CoA condense to form acetoacetyl-
CoA catalyzed by cytosolic thiolase. AcetoacetylCoA condenses with
a further molecule of acetyl-CoA catalyzed by HMG-CoA synthase
to form HMG-CoA, which is reduced to mevalonate by NADPH
catalyzed by HMG-CoA reductase.
• These first two reactions are catalyzed by thiolase and HMG-CoA
synthase,respectively.

10. Stage 2 Conversion of Mevalonate to Two
Activated Isoprenes
• In the next stage of cholesterol synthesis,
three phosphate groups are transferred from
three ATP molecules to mevalonate.
• One is Isopentenyl pyrophosphate and
• Second one Dimethylallyl pyrophosphate

12. Stage 3 Condensation of Six Activated Isoprene
Units to Form Squalene
• Isopentenyl pyrophosphate and dimethylallyl
pyrophosphate now undergo a head-to-tail condensation,
in which one pyrophosphate group is displaced and a 10-
carbon chain, geranyl pyrophosphate, is formed (The
“head” is the end to which pyrophosphate is joined.)
• Geranyl pyrophosphate undergoes another head-to-tail
condensation with isopentenyl pyro phosphate, yielding
the 15-carbon intermediate farnesyl pyrophosphate.
• Finally, two molecules of farnesyl pyrophosphate join head
to head, with the elimination of both pyrophosphate
groups, to form squalene.

14. Stage 4 Conversion of Squalene to the Four-
Ring Steroid
• Squalene can fold into a structure that closely
resembles the steroid nucleus.
• Before ring closure occurs, squalene is
converted to squalene 2,3-epoxide by a mixed
function oxidase in the endoplasmic
reticulum, squalene epoxidase.

16. Step 5: Formation of Cholesterol
• The formation of cholesterol from lanosterol
takes place in the membranes of the endoplasmic
reticulum and involves changes in the steroid
nucleus and side chain.
• The methyl groups on C14 and C4 are removed to
form 14-desmethyl lanosterol and then
zymosterol.
• The double bond at C8–C9 is subsequently moved
to C5–C6 in two steps, forming desmosterol.
Finally, the double bond of the side chain is
reduced, producing cholesterol.

18. TRANSPORT OF CHOLESTROL
• Cholesterol and Other Lipids Are Carried on
Plasma Lipoproteins.
• Cholesterol and cholesteryl esters, like
triacylglycerols and phospholipids, are
essentially insoluble in water,yet must be
moved from the tissue of origin to the tissues
in which they will be stored or consumed.
• They are carried in the blood plasma as
plasma lipoproteins,

19. CHOLESTEROL IS EXCRETED FROM THE BODY IN THE BILE AS
CHOLESTEROL OR BILE ACIDS (SALTS)
• About 1 g of cholesterol is eliminated from the
body per day.
• Approximately half is excreted in the feces
after conversion to bile acids.
• The primary bile acids are synthesized in the
liver from cholesterol.
• The remainder is excreted as cholesterol.