Cholesterol in the body
There are major sources of liver cholesterol:
1.Diet 2.HDL (which transport cholesterol from
peripheral tissues to the liver)
3. De novo synthesis in the liver (from the scratch)
(Point 3) It is important to people who wants to lower their
cholesterol. Accordingly, managing diet is NOT enough for these
people because the body can synthesize it to keep its level
balanced.
There are major routes by which cholesterol leaves the liver:
1. VLDL (which transport cholesterol from the liver then it will
be converted to IDL then LDL which carries a lot of
cholesterol)
2. Releasing cholesterol into the bile
3. Converting cholesterol to bile acids/salts
The balance between cholesterol influx and efflux is not
precise, resulting in a gradual deposition of cholesterol in the
tissues, particularly in the endothelial linings of blood vessels.
Structure of cholesterol
Cholesterol is an amphipathic compound. (it has a
large hydrophobic region but with small hydoxyl
group which gives it polarity (hydrophilicity))
It is a 27-carbon molecule that consists of:
Four fused hydrocarbon rings (A–D) of 17 carbons
called the steroid nucleus (these rings make up the
nucleus of steroid molecules, so they are all
derived from cholesterol)
Steroid nucleus is common between all steroid, but it can be modified by adding
some groups
Vitamin D is an exception, it is derrived from cholesterol but it lacks this nucleus
Two methyl groups (C18 and 19)
Eight-carbon, branched hydrocarbon chain attached to carbon 17 of the D ring.
Ring A has a hydroxyl group at carbon 3.
Ring B has a double bond between carbon 5 and carbon 6.
, Generally, cholesterol doesn’t really exist as free
cholesterol. Most plasma cholesterol is esterified with a
fatty acid attached at carbon 3.
BY esterifying the hydroxyl group, the cholesterol will
become fully hydrophopic
Intestinal uptake of cholesterol is mediated by the Niemann-Pick C1-like 1 protein (NPC1L1),
which can be targeted by ezetimibe (drug used to reduce cholesterol absorbtion).
Remember: Niemann-Pick disease is one of the lysosomal storage dieases results from
sphingomyelinase dificiency
ABCG5/8 protein is an efflux transporter (carries cholesterol from enterocytes to the lumen)
Defects in the efflux transporter (ABCG5/8) result in the rare condition of sitosterolemia.
Cholestelol is well-absorbed by intestines, then it will be carried by chylomicrons
Mamalians are exclusively the only organisms that have cholesterol in their bodies while
other organisms have other steroids that is similar to cholesterol
Plant sterols (phytosterols) are poorly absorbed by humans (5% vs. 40% for
cholesterol) and are actively transported back into the intestinal lumen.
However, Plant sterols can compete cholesterol in absorbrion thus
reduce the absorption of dietary cholesterol.
Having plants sterols is considered one of dietary strategies to
reduce plasma cholesterol levels.
(phytosterols)
NOTE: it is not really that efficient to control your cholesteol level
through diet because the body can synthesize it.
There are major sources of liver cholesterol:
1.Diet 2.HDL (which transport cholesterol from
peripheral tissues to the liver)
3. De novo synthesis in the liver (from the scratch)
(Point 3) It is important to people who wants to lower their
cholesterol. Accordingly, managing diet is NOT enough for these
people because the body can synthesize it to keep its level
balanced.
There are major routes by which cholesterol leaves the liver:
1. VLDL (which transport cholesterol from the liver then it will
be converted to IDL then LDL which carries a lot of
cholesterol)
2. Releasing cholesterol into the bile
3. Converting cholesterol to bile acids/salts
The balance between cholesterol influx and efflux is not
precise, resulting in a gradual deposition of cholesterol in the
tissues, particularly in the endothelial linings of blood vessels.
Structure of cholesterol
Cholesterol is an amphipathic compound. (it has a
large hydrophobic region but with small hydoxyl
group which gives it polarity (hydrophilicity))
It is a 27-carbon molecule that consists of:
Four fused hydrocarbon rings (A–D) of 17 carbons
called the steroid nucleus (these rings make up the
nucleus of steroid molecules, so they are all
derived from cholesterol)
Steroid nucleus is common between all steroid, but it can be modified by adding
some groups
Vitamin D is an exception, it is derrived from cholesterol but it lacks this nucleus
Two methyl groups (C18 and 19)
Eight-carbon, branched hydrocarbon chain attached to carbon 17 of the D ring.
Ring A has a hydroxyl group at carbon 3.
Ring B has a double bond between carbon 5 and carbon 6.
, Generally, cholesterol doesn’t really exist as free
cholesterol. Most plasma cholesterol is esterified with a
fatty acid attached at carbon 3.
BY esterifying the hydroxyl group, the cholesterol will
become fully hydrophopic
Intestinal uptake of cholesterol is mediated by the Niemann-Pick C1-like 1 protein (NPC1L1),
which can be targeted by ezetimibe (drug used to reduce cholesterol absorbtion).
Remember: Niemann-Pick disease is one of the lysosomal storage dieases results from
sphingomyelinase dificiency
ABCG5/8 protein is an efflux transporter (carries cholesterol from enterocytes to the lumen)
Defects in the efflux transporter (ABCG5/8) result in the rare condition of sitosterolemia.
Cholestelol is well-absorbed by intestines, then it will be carried by chylomicrons
Mamalians are exclusively the only organisms that have cholesterol in their bodies while
other organisms have other steroids that is similar to cholesterol
Plant sterols (phytosterols) are poorly absorbed by humans (5% vs. 40% for
cholesterol) and are actively transported back into the intestinal lumen.
However, Plant sterols can compete cholesterol in absorbrion thus
reduce the absorption of dietary cholesterol.
Having plants sterols is considered one of dietary strategies to
reduce plasma cholesterol levels.
(phytosterols)
NOTE: it is not really that efficient to control your cholesteol level
through diet because the body can synthesize it.
