[FMS] NAM - lipid synthesis and transport in blood Flashcards
what happens in fatty acid synthesis
- acetyl coA combines with oxaloacetate to get citrate, citrate can leave the mitochondrial to get into cytoplasm where citrate splits into acetyl coA and oxaloacetate
- acetylCoA turns into Malonyl CoA, catalysed by acetylCoA Carboxylase enzyme which is activated by insulin (THIS IS KNOWN AS THE 1ST STEP IN FA SYNTHESIS WHICH IS A RATE LIMITING STEP, SIGNIFYING THE FED STATE)
- hexose phosphate shunt provides NADPH for fatty acid synthesis
- fatty acid synthase extends the carbon chain of the fatty acid to a 16 carbon fatty acid chain known as palmitic acid, H20, and CO2
where does fatty acid synthesis take place?
liver
what activates Malonyl CoA, what state does Malonyl CoA signify?
- Malonyl CoA is activated by insulin, and it signifies the fed state.
what is needed for fatty acid synthesis, what is it provided by?
- NADPH is needed for fatty acid synthesis.
- This is provided by the hexose monophosphate shunt.
How do you synthesise triaglycerols
The 3 fatty acids form ester bonds with the glycerol phosphate.
Outline the lipoprotein structure including what molecules makes up the inner core and the outer shell
The inner core includes:
- Triglycerides and cholesterol esters
The outer shell includes:
- A single layer of phospholipids
- Cholesterol
- Apoproteins
What are the 4 classes of lipoproteins?
Chylomicrons
Very Low Density Lipoprotein (VLDL)
Low Density Lipoprotein (LDL)
High Density Lipoprotein (HDL)
what class of lipoproteins do chylomicrons carry?
dietary TAG
what class of lipoproteins do VLDLs carry?
endogenous TAG
what class of lipoproteins do LDLs carry?
cholesterol to tissues
what class of lipoproteins do HDLs carry?
cholesterol from tissues to the liver
Explain the transport of exogenous fat
1. chylomicron in small intestine made up of TAG, C, CE, APO B-48
2. APO C II and APO E added from HDL
3. Chylomicron goes into capillary and is broken down by LPL (LPL is activated by APO C II and insulin, but APO CII can activate it on its own without insulin)
4. chylomicron broken down into fatty acids and glycerol. fatty acids go to tissue to be turned into TAG. glycerol goes to liver
5. you also have chylomicron rememnant which is made up of TAG, C, CE, APO E and APO B 48 - this can be recognised by APO E receptor on liver, and the chylomicron remenant is taken up by the liver
IN DEPTH EXPLANANTION:
- After eating these chylomicrons, they are hydrolysed and then put back together in the small intestine.
- So you have triacylglycerol, cholesterol ester and cholesterol - this also has the apoprotein (apo B-48) added to it
- This goes into circulation and is picked up by more apoproteins including apo E and apo C-2
- Lipoprotein lipase, which is present in the lining of the capillary, breaks down the tricylglycerol. The resulting fatty acids move into the tissue and are reesterified to form triacylglycerol.
- The glycerol from the TAG cannot be used by the adipocyte (the tissue) because it doesn’t have glycerol kinase - so it goes to the liver instead.
- We are also left with a chylomicron remnant as not all the triaglycerol is removed. This goes to liver and the apo E is recognised by the apo E receptor and is taken into the liver.
-Apo C-2 activates lipoprotein lipase. Insulin also activates lipoprotein lipase. However apo C-2 activates it independently of insulin.
Outline the transport of endogenous fat
1. VLDL is in liver, made up of TAG, CE, C and B-100
2. APO C II and APO E added by HDL
3. VLDL goes into capillary and broken down by LPL which makes fatty acids and glycerol.
4. the fatty acid goes to tissues to be turned into TAG, the glycerol goes to the liver.
5. you also have an IDL made (intermediate lipoprotein)
6. the APO C II and APO E on the IDL goes back to the HDL, this leaves the LDL made up of TAG, CE, C and B-100
7. half of the LDL goes to peripheral tissue, the other half goes back to the liver via the B-100 receptor
IN DEPTH EXPLANANTION
- When we make the fat in the liver, the apoprotein that is added to it is B-100.
- This goes into the circulation and is picked up by more apoproteins including apo E and apo C-2
- Lipoprotein lipase, which is present in the lining of the capillary, breaks down the tricylglycerol. The resulting fatty acids move into the tissue and are reesterified to form triacylglycerol.
- The glycerol from the TAG cannot be used by the adipocyte (the tissue) because it doesn’t have glycerol kinase - so it goes to the liver instead.
- We are now left with the TAG, CE and C as well as the apoproteins C-2, E and B-100 - this is the intermediate density lipoprotein (IDL).
- Apo E and C-2 are returned to the HDL.
- This forms LDL, half goes to the liver and the other half to the peripheral tissue. There are B-100 receptors on both the liver and peripheral tissue.
Explain the transport of HDL
- APO A1 synthesised by both the liver and the small intestine. It serves as the primary protein component of HDL.
-
Cholesterol
Esters and Phospholipids formed. (phospholipids such as phosphatidylcholine) - Action of LCAT: Lecithin-cholesterol acyltransferase (LCAT) catalyzes the transfer of a fatty acid from phosphatidylcholine (or LPC) to the hydroxyl group of cholesterol, forming cholesterol esters. This process stabilizes the HDL particle and promotes its maturation.
- Cholesterol ester transfer protein (CETP) facilitates the exchange of cholesterol esters and triglycerides between HDL and other lipoprotein particles, such as VLDL (Very Low-Density Lipoprotein).
- The liver expresses a receptor called scavenger receptor class B type 1 (SR-B1), which binds to HDL particles. SR-B1 facilitates the selective uptake of cholesterol esters from HDL into liver cells.
This process helps in the removal of excess cholesterol from peripheral tissues and its transport back to the liver for further metabolism or excretion.
Outline cholesterol synthesis
- We make cholesterol ourselves from acetyl CoA
- Acetyl CoA + Acetoacetyl CoA goes to HMG-CoA.
- This then goes to mevalonate, and this reaction is catalysed by HMG-CoA reductase.
give 2 reasons why LDL receptors important.
- LDL receptors are very important because:
- They recognise B-100
- They remove LDL from the circulation (by receptor mediated endocytosis).
What is Hypertriglyceridaemia
when you have high levels of chylomicrons or VLDL
What are examples of genetic hyperlipoproteinaemias?
REMEMBER:
defective LDL= high LDL in blood (hypercholesterolemia)
anything else is as a results of high chylomicrons and VLDL
how does cholesterol control its own synthesis/ how is cholesterol synthesised?
- The LDL particles are recognised by the B-100 receptor.
- This causes the endocytosis of the lysosomes to release cholesterol.
- The cholesterol gets into the nucleus and it inhibits the synthesis of cholesterol synthesising enzymes.
- So cholesterol controls its own synthesis and the number of LDL receptors on the cell surface.
