Lipids Flashcards
Which lipids of HMG derivatives?
ketone bodies, cholesterol, bile acids and salts
What are the fat soluble vitamins?
A, D, E and K
Which molecule can transport fatty acids in the blood?
Albumin
When are TAGs utilised?
exercise, starvation and pregnancy
Which enzyme mobilises TAG?
Hormone sensitive lipase
What does it mean that TAG is stored in a dynamic state?
TAG is constantly being formed and broken down.
How are fatty acids activated?
linking to coenzyme A by fatty acyl coA synthase
investment of ATP
in cytoplasm
Which membrane is the carnitine shuttle on?
The inner mitochondrial membrane
Why is the carnitine shuttle needed?
Because coenzyme A is too big to cross the inner mitochondrial membrane
How does the carnitine shuttle work?
Carnitine is combined with acyl and the coA is released. Acyl carnitine is transported across the inner mitochondrial membrane via the shuttle. Acyl carnitine is broken down to reform acyl coA.
Which enzyme is required for the carnitine shuttle?
Carnitine acyltransferase
Which molecule inhibits the carnitine shuttle?
Malonyl-coA
What can defects in the shuttle system cause?
exercise intolerance and lipid droplets in muscle
Where does beta oxidation not occur and why?
brain, RBCs and WBCs
Brain = fatty acids cannot cross the blood brain barrier
cells = do not have mitochondria
How does beta oxidation work?
The removal of 2 carbons per cycle. Hydrogen is transferred to NAD+ and FAD. There is no ATP synthesis and the process stops in the absence of oxygen.
Where is glycerol metabolised?
Liver
Which enzyme activates glycerol and what is the product?
enzyme = glycerol kinase product = glycerol phosphate
What can glycerol phosphate be used for?
TAG synthesis or DHAP synthesis
Name the 3 ketone bodies
acetoacetate, acetone and beta-hydroxybutyrate
Where are ketone bodies synthesised?
Mitochondria in the liver
Which enzyme needs to be activated for ketone body synthesis?
HMG-CoA Lyase
Which enzyme is inhibited during ketone body synthesis?
HMG-CoA Reductase
Which hormone activates HMG-CoA lyase?
Glucagon
Are ketone bodies water soluble?
Yes
What happens to fatty acids with an odd number of carbon atoms?
beta-oxidation until a 3 carbon molecule is formed
carboxylation to methyl malonyl coA
rearranged to succinyl coA (vitamin B12 cofactor)
Which lipids are fatty acid derivatives?
TAGs and phospholipids
How are lipids transported in the blood?
Fatty acids can be bound to albumin. However 98% of lipids are carried as lipoprotein particles.
What value should plasma cholesterol be below?
5mmol/L
What is the difference between a micelle and a liposome?
Micelle = one layer of phospholipids Liposome = bilayer of phospholipids
Where does cholesterol come from?
some in the diet but most synthesised by liver
What is cholesterol a precursor to?
steroid hormones and bile acids
How is cholesterol transported?
As cholesterol ester.
Cholesterol + fatty acid
What are the main carriers of fat?
chylomicrons and VLDLs
What are the main carriers of cholesterol esters?
ILDL, LDL and HDL
Which lipoprotein particle has the biggest diameter?
Chylomicron
Which lipoprotein particle has the smallest diameter?
HDL
How many classes of apolipoproteins are there?
6 major classes
Name the major classes of apolipoproteins
A, B, C, D, E and H
What are the roles of apolipoproteins?
maintain structural integrity, cofactor for enzymes and ligand for receptors
Where are chylomicrons loaded?
In the small intestine
What is the pathway for chylomicrons?
loaded in small intestine, enter lymphatic system, travel to thoracic duct, enter left subclavian vein, bind to lipoprotein lipase on adipocytes and muscle, release fatty acids, become chylomicron remnant then return to liver to be broken down
Which apolipoproteins do chylomicrons gain once they enter the blood?
apoC and apoE
Which apolipoprotein of chylomicrons binds to lipoprotein lipase?
apoC
When does a chylomicron become a remnant?
When TAG ~ 20% and apoC dissociates
What does apoE bind to?
LDL receptor on hepatocytes
What is the role of lipoprotein lipase?
Hydrolysis of TAG
Where and why is VLDL made?
Liver
Transport TAG
Which apolipoproteins does VLDL have and where are they added?
apoB100 - added in liver
apoC and apoE - added in blood
When does a VLDL become an IDL?
when the content is ~30%
What happens when IDL content is ~10%?
IDL loses apoC and apoE
becomes an LDL particle
What is the primary function of LDL?
Transport cholesterol from liver to tissues
What is the difference between LDL and IDL/VLDL?
LDL does not have apoC or apoE and therefore is not efficiently cleared by the liver.
What is receptor expression for a lipoprotein particle controlled by?
cholesterol content within the cell
Which of VLDL, IDL or LDL has the longer half life?
LDL has a longer half life
How are atherosclerotic plaques formed?
oxidised LDLs are taken up by macrophages
Enter into the tunica intima
transform into foam cells
form plaques
Where is HDL synthesised?
liver and intestine
Which lipoprotein particles can HDL bud off?
VLDL and chylomicrons
How does HDL fill up?
HDL accumulates phospholipids and cholesterol from cells lining blood vessels
hollow core fills
ABCA1 protein facilitates transfer of cholesterol to HDL
Which enzyme converts cholesterol to cholesterol ester?
LCAT
What is the function of chylomicrons?
transport dietary TAG from intestines to tissues
What is the function of VLDL?
transport of TAG synthesised in liver to adipose tissue
What is the function of IDL?
Precursor of LDL. Transport of cholesterol synthesised in the liver to tissues.
What is the function of LDL?
Transport of cholesterol synthesised in the liver to the tissues.
What is the function of HDL?
Transport of excess cholesterol from tissues to liver for disposal as bile salts.
What is a hyperlipoproteinaemia?
A raised plasma level of one of more lipoprotein class.
What causes Type I hyperlipoproteinaemia and how would you spot it?
defective lipoprotein lipase
chylomicrons present in fasting plasma sample
What causes Type IIa hyperlipoproteinaemia and what is it also called?
defective LDL receptor
familial hyperlipoproteinaemia
What are the clinical signs of hypercholesterolaemia?
high cholesterol in blood and cholesterol depositions
Where can cholesterol depositions occur?
eyelids, tendons and eyes
Which layer do foam cells build up in?
Tunica intima
How do you treat hyperlipoproteinaemias?
change diet: reduce cholesterol, reduce fats, increase fibre
increase exercise
stop smoking
take statins - reduce cholesterol synthesis
take bile salt sequestrants - liver must produce more bile salts and therefore use up more cholesterol
Why should a patient with hyperlipoproteinaemia increase their fibre intake?
More fibre means that the liver will make more bile salts and therefore more cholesterol is removed from the blood.
What is the problem with statins?
They have many side effects because they inhibit cholesterol synthesis early on in the process.
Why might a low protein diet affect lipid transport?
The liver cannot synthesise sufficient apolipoproteins to export the TAG it synthesises. Fatty liver may occur.
Define emesis
Vomiting
Define oedema
Increased net flow of fluid from plasma to tissues because of reduced oncotic pressure.
