Lipids Flashcards
(38 cards)
Are lipids more or less reduced that carbohydrates?
More reduced - so when oxidised they release more energy but this requires more 02
What are the 3 classes of lipids and give an example of each?
- Fatty acid derivatives e.g. fatty acids and TAGs, phospholipids
- Hydroxy-methyl-glutamic acid derivative (C6 compound) e.g. ketone bodies and cholesterol and bile acids and salts
- Fat soluble vitamins - ADEK
Where and how are TAGs stored?
They are stored in adipose tissues in anhydrous forms because they are hydrophobic.
Describe dietary TAG metabolism
- Lipids = fatty acids and glycerol
In SI converted into TAG again in GI tract. - Packaged into chylomicron, a lipoprotein particle - helps to stabilise the, during transport
- Released into general circulation in lymphatics and taken to adipose tissues and stored as triglycerol.
- When needed, FA released and carried to tissues as an albumin-FA complex.
How are FA’s catabolised?
FA acids activatedd by linking to CoA via Fatty acyl-coA synthase. Then transported across inner mitochondrial membrane via carnitine shuttle - this overcomes the fact that mitochondria is normally impermeable to FA.
Then various beta oxidative pathways where they lose a C2 each time. Reducing power generated. Then the C atoms of the fatty acids are converted to Acetyl-CoA to be used in other metabolism.
How is beta oxidation of fatty acids regulated?
Regulated by AMP and insulin
CAT1 inhibited by malonyl-CoA
Where does beta oxidation of fatty acids not occur?
The brain as FA can’t cross the BBB and also the RBC as no mitochondria.
How is the glycerol from TAGs metabolised?
TAGs broken down by pancreatic lipase in small intestine into FA and glycerol phosphate. This can be converted to Dihydroxyacetone phosphate and enter glycolysis as Glyceraldehyde 3P.
Glycerol phosphate to DHAP is catalysed by glycerol-3-phosphate dehydrogenase.
Lipid synthesis in adipose tissue needs glycolysis but the liver can directly phosphorylase glycerol.
What is the pKa of ketone bodies?
4 - makes the blood acidic
What are the 3 ketone bodies made in the body?
Acetone - not used as a fuel source
Acetoacetate
B-hydroxybutyrate
How do statin drugs work?
They prevent the formation of cholesterol from mevalonate from acetyl-coA by inhibiting the action of HMG-CoA reductase.
How is the production of ketone bodies regulated by the liver?
Increased by a low NAD+ status, or if the production of NADH inhibited (via isocitrate dehydrogenase or a-ketoglutarate dehydrogenase) because this inhibits the TCA cycle so shifts towards ketone body production.
How is ketone body synthesis regulated by insulin and glucagon in the fed state vs the starvation state?
When ratio is high in the fed state lease is inhibited and HMG-coA reductase is activated leading to cholesterol synthesis.
When ratio is low, lyase activated and reductase inhibited so moves towards ketone body synthesis.
Summarise how acetyl coA production ends with either cholesterol or ketone bodies
Acetyl-CoA is converted to HMG-CoA.
If in the fed state - cholesterol produced.
If in the starvation state - ketone bodies produced for use in muscle tissues.
How are lipids carried in the blood?
2% as albumin bound - usually FA
98% lipoprotein bound
What is the average amount of lipids in grams per litre of blood?
4-8.5g/L blood
Where does cholesterol come from, how is it transported and what are some of its uses?
Some from diet but most from liver. It is transported as a cholesterol ester with a fatty tail added and then in a lipoprotein.
Uses:
- membrane structure
- precursor in steroid hormone e.g. oestrogen and testosterone
- precursor of bile salts
What are lipoproteins?
Soluble proteins that transport lipids around the blood. They can take various structures e.g. a micelle with a phospholipid monolayer. You can get peripheral and internal types of lipoproteins. There are 5 different types.
What are the 5 different classes of lipoproteins?
- Chylomicrons - for dietary fats (largest in size)
- VLDL
- IDL
- LDL ‘bad cholesterol’
- HDL ‘good cholesterol’ - transports excess cholesterol from cells to the liver (smallest in size - high % protein)
Particle size inversely proportional to their density.
1 and 2 = main carrier of fats
3-5 = main carriers of cholesterol esters
How long are chylomicrons typically in the blood for after eating?
4-6hrs post eating
How is lipoprotein density measured?
Via flotation ultracentrifugation
What are apolipoproteins and what are their functions?
They are a particular class of proteins associated with each lipoprotein particle. They can be integral or they can be peripheral.
They help to package the lipid and they also are co-factors for enzymes and act as ligands for cell surface receptors.
How are chylomicrons metabolised?
They are loaded in small intestine and the ApoB-48 alipoprotein is added.
Chylomicrons travel to thoracic duct to left subclavian vein and ApoC and ApoE added once in the blood.
ApoC binds lipoprotein lipase on muscle and adipocyte cells and this causes release of the FA into the cell.
when TAG reduced to 20%, the ApoC dissociates from chylomicron and it becomes a chylomicron remnant. These return to the liver . LDL receptor on hepatocyte binds ApoE & remnant taken up by receptor mediated endocytosis. Contents released from lysosome for metabolism.
Describe VLDL metabolism?
Made in liver to transport TAGs to other tissues. ApoB100 added when formed and ApoC and E added from HDL particles in blood.
VLDL binds to lipoprotein lipase on endothelial cells In muscle and adipose tissue and start to become depleted of TAGs.
