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Summary Fat, cholesterol & atherosclerosis
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Samenvatting Marks' Basic Medical Biochemistry - Biochemistry (AB_1137)
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MARKS' BASIC MEDICAL BIOCHEMISTRY: A CLINICAL APPROACH SIXTH, NORTH AMERICAN EDITION BY MICHAEL A. LIEBERMAN PHD (AUTHOR), ALISA PEET MD (AUTHOR)
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Fat, cholesterol & atherosclerosis1. risk factors for developing atherosclerosis
Lipoproteins transport TG, cholesterol through the blood. We have different lipoproteins,
depending on their size and density. There is a very strong correlation between serum
cholesterol & getting CVD.
LDL contains a lot of cholesterol, therefore correlated through the CVD.
Atherosclerosis is a plaque full of cholesterol. LDL moves
free in subendothelial space, when levels are high of LDL,
oxidation of OxLDL, which are taken up by macrophages
on the receptors LOX-1 and CD36. Then they develop into
foam cells and become activated > leading to
proinflammatory cytokines > leading proinflammatory
environment. Deposit of a lot of immune cells, secrete
proteases > cleave all those foam cells > when it ruptures
> blood clotting
HDL reverse cholesterol to the liver > now can be converted into bile salts etc.
High HDL is protected from CVD, mutation in ApoA1 > risk of getting CVD is much higher.
Even when LDL is low, when HDL is low, your risk is big. The ratio LDL/HDL is used in the
clinic, the lower the better.
CRP is a better marker for CVD than cholesterol in women. CRP is made by the liver, when
there is inflammation. This CRP reaction is done by the cytokines (TNF-a and IL-6) that are
released by the fat tissue.
Metabolic syndrome = combination of risk factors to predict
changes of getting CVD. Like high cholesterol, insulin resistance,
obesity. When you are insulin resistance: increased APOB (LDL)
and decrease APOA1 (HDL), increased CRP
These people get NFLD = liver get lipid loaded, bc cannot be
transported anymore, leading to a lot of oxidative stress in the
liver > cannot make the lipoproteins anymore.
2. Cholesterol metabolism
Cholesterol is needed for all types of molecules. Can take up from the food, which is
transported as free cholesterol or packed into the TG. Pancreas produces enzymes that
extract cholesterol from the diet.
80% of the cholesterol is made by the liver. Body keeps tight
control of the levels. From acetyl CoA > cholesterol > become
membrane, bile salts or steroid hormones
Cholesterol synthesis: from Acetyl CoA > mevalonate by
HMG-CoA is COMMITTED step. Takes a lot of energy, therefore
the need to recycle cholesterol.
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