Cholesterol metabolism and health and disease Flashcards
what pathway are cholesterol and fatty acids absorbed
exogenous pathway
what happens to cholesterol and fatty acids in the exogenous pathway
Triglycerides are formed in the intestinal cells from free fatty acids and glycerol
Cholesterol is esterified
what do Triglycerides and cholesterol combine to form
chylomicrons
Once Chylomicrons enter the circulation where do they travel
travel to peripheral sites
In peripheral tissues, free fatty acids are released from the chylomicrons to be used as what
energy, converted to triglyceride or stored in adipose
In peripheral tissues, free fatty acids are released from the chylomicrons to be used as what
energy, converted to triglyceride or stored in adipose
what is the main site of LPL activity
adipose & mammary tissue, skeletal muscle, myocardium.
what do Endocytosed chylomicrons that are catabolized
by lysosomes do
release cholesterol for excretion as bile acids in bile
or incorporated into VLDL
what do Endocytosed chylomicrons that are catabolized
by lysosomes do
release cholesterol for
excretion as bile acids in bile
or incorporated into VLDL
what happens in the endogenous pathway
VLDL FORMS IDL or VLDL remnants.
What do LDL particles contain
a core of cholesterol esters and a smaller amount of triglyceride.
What is LDL is internalized by
hepatic and non-hepatic tissues.
In the liver, what is LDL converted into
bile acids and secreted into the intestines.
In non hepatic tissues, what is LDL used in
hormone production, cell membrane synthesis, or stored.
LDL is also taken up by macrophages and other cells which can lead to what
excess accumulation and the formation of foam cells which are important in plaque formation.
What is HDL
HDL is a heterogenous group of macromolecules with different physical properties and chemical components
What are the 2 subclasses of HDL
HDL2 and HDL3
What is the function of HDL
to reverse transport of cholesterol from different tissues to the liver for excretion
What is the function of HDL
to reverse transport of cholesterol from different tissues to the liver for excretion
What does Reverse cholesterol transport begins with
the removal of cholesterol from arterial foam cells
what happens to Cholesterol from non-hepatic peripheral tissues
is transferred to HDL by the ABCA1(ATP-binding cassette transporter).
what does ApoA-1 act as
an acceptor and the phospholipid component of HDL acts as a reservoir for the cholesterol.
what enzyme coverts cholesterol to cholesterol esters
The cholesterol is converted to cholesteryl estersby the enzyme LCAT (lecithin-cholesterol acyltransferase).
what does LCAT do
Cholesterol → cholesteryl esters catalysed by lecithin cholesterol acyltransferase (LCAT) in peripheral tissues
Where is ACAT2 found
found in both intestine and liver
Where is ACAT1 found
in all tissues
what is cholesterol
Most abundant steroid
It is amphipathic
Can be found in large concentrations in the brain, spinal cord, and liver
Liver is the most important site of cholesterol biosynthesis, although other sites include the adrenal glands and reproductive organs
what is the function of cholesterol
Serves as the major precursor for the synthesis
vitamin D3
steroid hormones (cortisol, cortisone, and aldosterone in the adrenal glands)
sex hormones (progesterone, estrogen, and testosterone).
what is CVD
CVD includes all the diseases of the heart & circulation including coronary heart disease, angina, heart attack, congenital heart disease and stroke
CVD is responsible for a ¼ of all deaths in the UK
About half of all deaths from CVD are from CHD and about a quarter are from stroke
CHD by itself is the most common form of heart disease, and the most common cause of death for both men and woman globally
The cost of CVD to the UK healthcare system in 2020 was £22.5 billion
what arteries relate to CHD
Disease involving the network of blood vessels (coronary arteries) surrounding and serving the heart
What plaques effect the coronary arteries
the accumulation of atherosclerotic plaques in coronary arteries that lead to a reduction in blood flow to the myocardium.
what does CHD lead to
myocardial infarction (MI) and sudden death
what is Atherosclerosis
Risk factors: unhealthy blood Chol; high BP; smoking etc
Thickening of the arterial wall; artery becomes occluded (blocked)
Begins in childhood with clinical symptoms in middle age or later
Leads to ischaemia (lack of nutrients and oxygen) to cells supplied by the artery
how do you lower blood cholesterol
Regular exercise
Reducing Chol & Sat fat
Drugs - HMG-CoA reductase inhibitors - statins -lovastatin (Mevacor) & atorvastatin (Lipitor)
what is a major cause of CHD
atherosclerosis
What are the 3 stages of plaque formation
- fatty streak
- plaque progression
- plaque disruption-unstable plaques will rupture leading to thrombus and possible thrombosis
what is angina
A narrowing of one or more coronary arteries, restricting the flow of blood to the heart
Pain occurs during physical activity and sometimes at rest
Crushing pain which may move to left arm or to the jaw
how is stroke manifested
cerebral arteries
how is myocardial infarction manifested
coronary arteries
how is leg pain, DVT, gangrene manifested
peripheral arteries
what is heart attack
- Acute Myocardial Infarction
- death, long term complications
- happens when one or more of the coronary arteries supplying blood to the heart muscle becomes suddenly blocked and Shortage of blood supply to heart muscle leads to tissue death
what is Arrhythmia
- Disturbance in heart rhythm leading to ineffective pumping
- Common cause of death in early stage heart attack
- Bradycardia describes a rate of less than 60 beats per minute
- Tachycardia usually refers to a heart rate of more than 100 beats per minute
what tool diagnoses arrhythmias
An electrocardiogram
what treats issues with the heart
pacemaker
what is heart failure
when the pumping mechanism is ineffective and can be sudden or over a long time
what are the symptoms of heart failure
Chest discomfort
Shortness of breath
Nausea
Light headed
what is cardiac arrest
- Heart stops pumping
- Ventricular fibrillation most common cause and can be related to CHD, cardiomyopathy, electrocution, lack of oxygen, drug misuse
- CPR and defibrillation used to treat
what is a stroke
disturbance to brain function caused by inadequate blood supply (cerebral infarction) or by direct damage by bleeding into the brain (cerebral haemorrhage)
what is vascular dementia
- Narrowing of small blood vessels in the brain
- Mini strokes – transient ischaemic attacks (TIA)
Degenerative condition causing confusion, memory loss, difficulty with speech and balance and personality change - > 65 years most common
what are common medications for cholesterol issues
Probucal: increases conversion of cholesterol to bile acids
Cholestyramine: sequesters bile acids for excretion. As the body loses bile acids, it replaces them by converting blood cholesterol to bile acids
what are statins
A class of drugs used to lower cholesterol levels
Inhibit the enzyme HMG-CoA reductase, which plays a role in the production of cholesterol in the liver
what diet should you follow to reduce CVD
Replace SFA with unsaturated fats,
Avoid trans fats
Eat 2 portions of fish per week
Increase fibre intake
