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CA (630,000)
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Lecture

BCH210H1 Lecture Notes - Nonsteroidal Anti-Inflammatory Drug, Oleic Acid, Amphiphile


Department
Biochemistry
Course Code
BCH210H1
Professor
Michael Baker

Page:
of 7
Chapter 2
Risk factors contributing to CAD
1. Age Group
2. Total Cholesterol level
3. HDL
4. BP after treatment; if no treatment- BP before treatment
5. Smoker/Non smoker
17 risk points for men and 25 for women means that there is a 30% chance of coronary artery disease in
10 years
Risk Category 3 Treatment target
High 10 years risk of CAD> 20% (considering
the above mentioned factors) OR
History of CVD OR
History of diabetes
LDL < 2.5 AND
Total cholesterol/ HDL ratio < 4
Moderate 10 years risk of CAD 11-19% LDL <3.5 AND
Total cholesterol/ HDL ratio < 5
Low 10 years risk of CAD < 11% LDL < 4.5 AND
Total cholesterol/ HDL ratio < 6
You can do a lipid scan of the body because lipids contribute to the formation of plaques in the
arteries- how****?
What is a lipoprotein?
LPs are small particles that have a shell of phospholipids, cholesterol and proteins, and a core
interior made up of cholesterol esters and triglycerides
Cholesterol travels in the blood in particles called lipoproteins
High content of lipoproteins hence mean high level of cholesterol and thus increase in risk
factor
Triglycerides (TG) are fatty acid esters of glycerol (2 fatty acids attached to a glycerol
backbone) – they are a major component in fat cells- also found in lipoproteins
They are the main form of fat storage
burn very brightly- oil heats up at the burst of flame
provide more energy than carbohydrates
Lipoprotein structure – used in the transport of cholesterol and TAG
Apolipoprotein B- 100 – found in LDL – is on the surface of the lipoprotein
They help to characterize
You need these particles of LDL to carry lipids otherwise they would cluster together
A shell of phospholipids
Cholesteryl ester (modified cholesterol) and Triacylglyceral in the core
Unesterfied cholesterol – found randomly within the phospholipids
Lipoproteins can be made in two ways
1. When you eat and digest fat in your intestine, cells lining the intestine (the digestive system)
take up and break down the fatty acid and cholesterol
They then use it to make triglycerides , cholesterol esters, and proteins- combined
lipoprotein called Chylomicrons (CM)
They are much bigger than LDL(produced by liver)
Also have a phospholipid cholesterol shell – amphipathic- allowing it to flow
They are released into blood for usage by tissues- supplies tissues with fatty acids from
their triglycerides
2. Also possible for other tissues such as liver to make different types of lipoproteins using
triglycerides, cholesterol, cholesterol esters and proteins
Livers can easily convert excess dietary carbohydrates to triglycerides (recall intestine
converts fat into TG) – excess sugar into fat
These liver lipoproteins are called VLDL – very low-density lipoproteins
VLDL are smaller and heavier than Chylomicrons but still effective carrier
VLDL are released by the liver and enter the blood
The loss of TG
VLDL and CM are attacked in the blood by an enzyme called lipoprotein lipase LPL
LPL is made by heart or fat tissues and they come out near the circulation and set a post in the
capillaries
It hydrolyzes tryglycerides – breaks up ester linkages- making fatty acids and glycerol
This is done by LPL posted on a stalk on a capillary, as it identifies the protein tag on
triacylglycerides
Fatty acids, an important byproduct, can then diffuse out to heart tissues as necessary
Thus both CM and VLDL decrease in size
Both small CM and LDL (smaller denser lipoproteins than VLDL) are supposed to be absorbed
by the liver and degraded, but prolonged elevated levels in the blood can create problems
Lipoproteins
Chylomicrons – largest in size with mostly triacylglycerides
**Triacylglyceides = triglycerides?
VLDL - 2nd largest – mostly triacylglycerides but also some cholesterol and cholesterol ester
LDL- made after degrading TAG- what puts you at risk- mostly cholesterol + chol. Ester
HDL – a mixture of both low levels of cholesterol (10-30%) and low level of TAG (5-10%)
HDL is good because it picks up cholesterol and brings it back to the liver
HDL like VLDL is also made by liver
It goes out and picks up cholesterol and brings it back to the liver where it is engulfed
and removed
Liver
Clearing house for cholesterol- also synthesizing house of cholesterol?
Rich in cholesterol
Bile carrying cholesterol goes into the intestine and eventually outside the body – thus
removing cholesterol (no need for degradation)
Muscles don't have bile so can't get rid of cholesterol
LDL
enriched in cholesterol and cholesterol esters
high LDL = high cholesterol = high risk
function: to transport cholesterol from the liver to other tissue
Liver surface proteins called the LDL receptor recognizes LDL ( just like the remnant receptors
that recognize chylomicrons)
These receptors bind to LDL and allow its uptake by liver cells where they are digested by the
lysosomal system ( after cholesteryl oleate and proteins are separated)
Receptors are then recycled back to the plasma membrane
LDL thus enter the cell via receptors through a process called receptor mediated endocytosis
Receptor mediated endocytosis- LDL binding, internalization- lysosomal hydrolysis
If the LDL receptor is impaired, it will actually promote a rise in the cholesterol, especially following
high VLDL
LDL levels remain elevated in the blood
this problem is called hypercholesterolemia – too much cholesterol in the blood- indicator of
high risk cardiovascular disease
This problem is often inherited- FH = familal hypercholestero,ia
It could be that the receptors aren't working (smoking, eating habits) or simply that you
have fewer receptors if you have one bad copy of the gene (Aa)
LDL particles if prolonged in the circulatory system (as they are not being sucked up by receptor
mediated endocytosis, it increases the chance of going into the artery wall.
LDL arterial pathology- artherosclerotic plaque ***Only in muscle cells?
LDL can be modified by oxidation reactions- promotes LDL entry into the arteries
If you have high LDL levels + you smoke -(increase oxidated LDL), it means that LDL will
be taken up by arteries more often instead of the liver. This will increase your risk of getting
CAD or a stroke
Arteries cannot handle the fat in LDL well
Also cholesterol which is difficult to degrade -can't get out of the artery wall- it's stuck inside,
making the situation worse
This is because artery is not well supplied with blood capillaries coming to the outside
With LDL coming in, pressure builds up and the exit blood capillaries flatten out
With low diffusion of LDL out, cholesterol accumulates as LDL particles are trapped in
muscle cells
These stuck oxidated LDL in arteries trigger inflammatory response
They bind to connective tissues and release signal traces to attract cell white blood cells to enter
White blood cells act as macrophages and eat up LDL particles but it can degrade everything
other than cholesterol
The macrophage gets bigger and bigger to form foam cell
The foam cell tries leaving but it's too big (so while white blood cells could come in they can't
go out)
Eventually the foam cell dies and dumps all its cholesterol against the artery wall
Cholesterol and proliferation muscles building up (proliferation is turned on by cholesterol
being dumped on the artery wall)
Smooth muscle also produce connective tissue spread over the artery wall forming a cap
Now instead of a smooth wall you have a bump causing the formation of a thrombus from
platelets to become activated
Blood will start spiraling when it hits the bump, reactivating particles in the cell called platelets
This causes stenosis, turbulence in the blood flow, aggregation in platelets in thrombus
Thrombus breaks off into embolous – takes off speech
After years of buildup, the cholesterol rich lipid pool and connective tissue cap form a large
Atherosclerotic plaque
The blood consists of:
Red blood cells
white cells
Platelets
important in blood coagulation as the cells stick together when they are activated