LING 530 Lecture Notes - Lecture 2: Zipper, Ethyl Group, Extracorporeal
27 Jun 2018
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Diet
Fried egg contains 250 mg of cholesterol
Most food contains triacyl glycerols and lesser cholesterol
How do you transport fat in the aqueous medium of plasma? (Especially if you are an insect with
a primitive mouth and need to transport it to the winged muscles?) you need a gut, you need to
absorb the fat (triacyl glycerol+cholesterol and you need to attach it to a medium that will
transport it? You will need a spherical structure that will contain triacyl glycerol+cholesterol and
it needs to be water soluble-an interface needs to be there separating the fat and the water
Introduction
Why is studying lipid metabolism important?
Because the biggest cause of death around the world- heart disease
What happens when you have too much cholesterol?
Artery has a layer of muscle in the middle to allow it to constrict-give it a tone
Endothelium keeps the artery rigid
Artherosclerosis-layer of fat in the artery- blood is not able to deliver enough oxygen due to fat
clog in arteries
Copy number variation- Large deletions of segments of gene called copy number variant and is seen in
all chromosome- most of these mutations are benign unless they are VERY LARGE DELETIONS.
Familial hypercholesterolemia- If diagnosed and treated early, you can live a normal life
Low HDL cannot be cured
Heart disease risk factors- cigarette (biggest risk factor), hypertension, High LDL-Cholesterol (apo
B), Low HDL-Cholesterol, male sex, increasing age, pre-existing atherosclerosis
The more risk factors you accumulate, the exposure time increases
Leading cause of death in women after menopause- heart disease
Rate of death in woman breast cancer: heart disease – 1:9 (Why is heart disease in women NOT
given more importance then? A woman of 90 dying due to heart disease at 90 is not as
scientifically intriguing or medically important as a younger woman dying of breast cancer-that
is why society does not give it an importance)
Higher the cholesterol-higher the rate
Mendelian randomization- Higher the C reactive protein-higher the chance of heart disease- is
this a causal relationship? A single nucleotide polymorphism in CRP gene causes CRP levels to go
up- Genome wide association studies are done between two groups-one with low CRP and with
high CRP-If you a polymorphism in the CRP gene-each of the polymorphism increases CRP a little
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find more resources at oneclass.com
bit-but epidemiology says that risk of heart disease increases by 20%-but genome wide
association studies doesn’t say so-if the bar is on the left of the line- decreased risk and vice
versa-based on this it, you can disprove that associations is related to causality
Chromosome 9q21-strongly associated with heart disease-discovered 11 years ago-but the gene
on this chromosome responsible for the disease has not been identified yet
Lipid-any molecule insoluble in water and soluble in organic solvent
Take blood-spin it- you will find RBCs, WBC’s and plasma
Plasma contains water, CBH’s, amino acids, nucleic acids and lipids
Most of the plasma contains mostly lipids
The lipids are in the form of sterol lipids (most of them), glycerol phospholipid, little bit of
fatty acids, complexity of lipids is huge
Every lipid comes from acetyl coA
Study the structure of cholesterol, glycerolipids, glycerophospholipids
Cholesterol- only animals have cholesterol, we need it for the rigidity of our cell membranes
All other organisms like plants, bacteria etc. have sterols (plants have phytosterols, bacteria
have precursors of cholesterol)
Each of the carbons in the fatty acid can be used for energy in the mitochondria
Phosphotidyl choline- seen in egg yolk
Triacyl glycerol- glycerol+three fatty acid chains- it is in the form of a lipOprotein- spherical
macromolecule-core of cholesterol esters, triacyl glycerides
There is an absorption of fat through the gut- enclosed within the chyomicron-chlyomicron
contains a lot of triglycerides and very little cholesterol
Lipoprotein lipase degrades the triglycerides into individual fatty acid molecules which are
used in the tissues for energy storage
Fat is not always burnt – This is the exogenous pathway
How do you maintain energy when you are fasting? Stored fat will go back to the liver-liver
will put out a very low level density protein (VLDL),
Liver is not allowed to keep fat- greater overeating, greater the release of fat by the liver
and greater the chances of disease
LDL mostly contains cholesterol esters-humans are the only animals to have LDL
Conrad Bloch-characterized all enzymatic steps of cholesterol biosynthesis (33 or so steps
involved)-he came across may molecules that are medically important
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find more resources at oneclass.com
All living creatures have some form of sterol in their membrane
Cholesterol contributes to rigidity of plasma membrane (biggest function)
Brown and Goldstein- found the LDL receptor-how does a cell incorporate a very large
molecule? LDL receptor takes up LDL from the plasma into the cell by receptor mediated
endocytosis (discovered in the 1970s)-They got a Nobel Prize for this
Cholesterol accumulates in the joints of the hands-xanthomas
Massive depositions of cholesterol in the skin is usually orange-due to beta carotene in
cholesterol
What does HDL do? VLDL transports triglycerides-HDL transport cholesterol from the
liver/gut to a tissue that needs it for hormone synthesis (gonads, adrenals glands, mammary
glands etc.)-HDL is assumed to extract HDL from certain cells like macrophages and bring it
back to the liver
Exogenous pathway-chylomicrons to liver
Endogenous pathway-mediated by VLDL
There is also a reverse cholesterol transport pathway
Higher the triglyceride level, higher the chance of the heart disease-but association does not
suggest causality
When we look at the triglyceride levels, higher levels can give immediate pancreatitis but
not heart disease
Endoplasmic reticulum in the liver is where VLDL particles are made-they go to the golgi
If you try to block this pathway, where at the fatty acids going to go?
Apolipoprotein B (Apo B)-reflects the number of bad particles in plasma- there’ fat around
it-if there is not fat to put around it, it will get digested by the proteasome
Liver can make fatty acids by the fatty acid synthetic cycle- will be convert to triacyl glycerols
and secreted by VLDL
Insulin allows the synthesis of VLDL
Hormone sensitive lipase- helps to mobilize fat from a tissue into the VLDL
Liver will continuously put out VLDL because it cannot store fat
Triglyceride concentration should be less than 2 mmol/Ls
Between 2-10, MODERATELY ELEVATED
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Most food contains triacyl glycerols and lesser cholesterol. You will need a spherical structure that will contain triacyl glycerol+cholesterol and it needs to be water soluble-an interface needs to be there separating the fat and the water. Because the biggest cause of death around the world- heart disease. Artery has a layer of muscle in the middle to allow it to constrict-give it a tone. Artherosclerosis-layer of fat in the artery- blood is not able to deliver enough oxygen due to fat clog in arteries. Copy number variation- large deletions of segments of gene called copy number variant and is seen in all chromosome- most of these mutations are benign unless they are very large deletions. Familial hypercholesterolemia- if diagnosed and treated early, you can live a normal life. Heart disease risk factors- cigarette (biggest risk factor), hypertension, high ldl-cholesterol (apo. B), low hdl-cholesterol, male sex, increasing age, pre-existing atherosclerosis. The more risk factors you accumulate, the exposure time increases.
