Cholesterol Flashcards
What is a steroid
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What is the structural function of cholesterol
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What is the metabolic function of cholesterol
- steroid synthesis
- bile acid precursor
- vitamin d3 precursor
How is cholesterol present in tissues and plasma
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How is cholesterol transported in plasma
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What is De novo synthesis
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What is the central role of the liver in cholesterol balance - what are the sources of hepatic cholesterol
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Where can we obtain dietary cholesterol - how much of it do we absorb, how much do we excrete
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Does lowering cholesterol in diet have an affect on blood cholesterol
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What is the structure of Cholesterol
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What type of lipid is cholesterol
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How is Cholesterol in serum
.
Describe Cholesterol transport in serum - chylomicrons
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Describe Cholesterol transport in serum - VLDL and LDL
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Describe Cholesterol transport in serum - HDL
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Endogenous and Exogenous pathway??
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What is the normal range of cholesterol in serum
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At what ranges of cholesterol indicate low risk of coronary heart disease, moderate risk and high risk
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What are the reference ranges of α-cholesterol
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How is LDL usually calculated - when is it not accurate
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How can you estimate the risk of CHD
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What was the Framingham study
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What type of conditions can increased cholesterol lead to
Increased CholesTerol - Thyroid gland low activity
What type of conditions can decreased cholesterol lead to
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In what organs is cholesterol synthesised
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What is the main substrate for Cholesterol Synthesis
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What is required for Cholesterol synthesis to take place
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What are the 5 steps of Cholesterol synthesis
1. Synthesis of HMG-CoA and formation of mevalonate (C6) 2. Formation of active isoprenoid units (C5) 3. Synthesis of squalene (С30) 4. Oxidation and cycling of squalene to lanosterol (С30) 5. Formation of cholesterol (С27).
Where does cholesterol synthesis start
.
Describe step 1 of cholesterol synthesis - what enzymes are used, where are they located, domains of enzymes, structures
Synthesis of HMG-CoA and formation of
mevalonate (C6)
Describe step 2 of cholesterol synthesis - structures, enzymes,
Formation of active isoprenoid units (C5)
Describe step 3 of cholesterol synthesis - names
Synthesis of squalene (С30)
Describe step 4 of cholesterol synthesis - names
Oxidation and cycling of squalene to
lanosterol (С30)
Describe step 5 of cholesterol synthesis - names
Formation of cholesterol (С27).
What is the key regulatory enzyme in Cholesterol Synthesis
.
What is the half life of HMG-CoA reductase
.
Describe how HMG-CoA reductase can be regulated
Transcriptional regulation - incl. hormonal regulation
covalent modification
proteolytic degradation of HMG-CoA Reductase
Describe covalent modification of HMG-CoA reductase
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Describe Transcriptional regulation of HMG-CoA reductase
- what is suppressed, SREBP-2, SCAP, Proteases
Describe the proteolytic degradation of HMG-CoA Reductase
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Describe the hormonal regulation of transcriptional level regulation of HMG-CoA Reductase
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Describe LDLR (receptors) - what do they recognise, what do they bind to, where are they localised, how are LDLs taken up in the cell
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What occurs during endocytosis of LDL in cells - insertion of cholesterol in cells
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What are the effects of cholesterol in cells
ACAT
When LDLs enter the cell, what enzyme is used to convert CE into cholesterol
Lysosomal cholesterol esterase
Describe LRP (LDL receptor related protein) - what they recognise, where they are highly expressed, what does not affect the synthesis of this receptor,
- α2-microglobulin, tPA.
- other LDLR
Describe the Macrophage Scavenger Receptor
- other LDLR
- Oxidized low-density lipoprotein (OxLDL)
What are statins and how do they affect cholesterol serum levels
HMG-CoA Reductase Inhibitors
What are the side effects of statins
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What is the mechanism of action of statins
Statins act by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway
similar in structure to HMG-CoA on a molecular level
What are bile acid sequestrants - %, mechanism of action
Bile acid sequestrants bind bile acids in the intestine and increase the excretion of bile acids in the stool. This reduces the amount of bile acids returning to the liver and forces the liver to produce more bile acids to replace the bile acids lost in the stool. In order to produce more bile acids, the liver converts more cholesterol into bile acids,
What are the side effects of bile acid sequestrants
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What is Niacin - %, mechanism of action,
.
What are the side effects of Niacin
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What are Fibrates (Fibric Acids) - %, mechanism of action
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What are the side effects of Fibrates
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What drugs affect cholesterol serum levels
Statins
Bile acid sequestrants
Niacin
Fibrates