Lipid synthesis Flashcards
What is the first step of fatty acid synthesis?
Transport of acetyl CoA to cytosol by the citrate shuttle
What is the function of the citrate shuttle?
Transports acetyl CoA and NADPH into the cytosol from the mitochondria
When is citrate high?
a) fasted state
b) fed state
b
Why can citrate move into the cytosol?
It has a carrier
What happens to citrate when it enters the cytosol?
Splits into acetyl CoA and oxaloacetate
What is the fate of acetyl CoA from citrate?
Substrate for fatty acid synthesis
What is the fate of oxaloacetate from citrate?
Converted to pyruvate and NADPH is made.
Pyruvate enters the mitochondria
What is the 2nd step fo fatty acid synthesis?
Activation of acetyl CoA - carboxylation to from malonyl CoA.
Acetyl CoA + CO2 –> Malonyl CoA
(ATP –> ADP)
Acetyl CoA Carboxylase
What enzyme catalyses the activation of acetyl CoA?
Acetyl CoA carboxylase
What enzyme catalyses the sequential addition of 2 carbon units?
Fatty acid synthase
What is the structure of fatty acid synthase?
It is a dimer that contains 2 acyl carrier proteins
How does acetyl CoA interact with fatty acid synthase?
Each acyl carrier protein on the fatty acid synthase accepts malonyl CoA and acetyl CoA.
The CoAs are released
What happens once the CoAs are released from he fatty acid synthase acyl carrier protein complex?
Acetyl ACP is cleaved off and transferred to malonyl ACP in a condensation reaction. CO2 is released.
This forms acetoacetyl ACP
What 3 steps elongate acetoacetyl ACP?
Reduction, dehydration, reduction
How does the chain get elongated further?
The elongated chain takes the place of acetyl CoA in the cycle
What activates acetyl CoA carboxylase?
Citrate and ATP allosterically, insulin by de-phosphorylation
When does fatty acid synthesis stop?
When 16 carbon chain is formed.
Cleaves off ACP and forms palmitate
What inhibits acetyl CoA carboxylase?
Palmitate by product feedback.
Glucagon and adrenaline by phosphorylation
Where does phosphorylation occur beyond C16?
Endoplasmic reticulum
How are double bonds introduced?
Oxidases
What is cholesterol a precursor of?
Bile and all steroid hormones
How is cholesterol formed and where?
In cytosol.
From HMG using HMG-CoA reductase
How are fatty acids transported in the blood stream?
Bound to albumin
How are triglycerides and cholesterol transported in the blood stream?
Bound to lipoproteins
What are the 5 classes of lipoproteins?
Chylomicrons VLDL IDL LDL HDL
Describe the general structure of lipoproteins?
Phospholipid circle with hydrophobic core and store triglycerides and esterified cholesterol in the centre
What is the function of chylomicrons?
Transport triglycerides
What do chylomicrons contain?
Triglycerides, cholesterol and apo protein B48
What occurs to chylomicrons hone they enter the blood?
HDL donates apo CII and E
This activates lipoprotein lipase not he endothelial surface of vascular system
What happens to chylomicrons when triglyceride levels are low?
Return CII and E back to HDL and then go to the liver to be degraded
What is the function of VLDL and IDL?
Transport lipids from the liver to the rest of the body
Where is VLDL made?
Hepatocytes
What do VLDL contain?
TAG, cholesterol and apo100
What occurs to VLDL when it enters blood?
HDL donates apo CII and E
Lipoprotein lipase activated, TAG hydrolysed into glycerol and fatty acids
How does VLDL become IDL?
TAG is hydrolysed, as they off load TAG become IDL.
CII returned to cholesterol
What happens to IDL remaining in circulation?
Receives cholesterol from HDL. Donates phospholipid and ATG in return to become LDL
What is the function of LDL?
Transport cholesterol to tissues
What happens to LDL in circulation?
Enters cells by endocytosis and fuses with lysosomes to release cholesterol
What does HDL contain?
Phospholipids and apo proteins
What is the function of HDL?
Accepts free cholesterol from peripheral cells and esterifies it and passes to VLDL, IDL, LDL
What causes genetic dyslipidaemias?
Elevated TAG or cholesterol due to abnormal lipid metabolism
What causes abnormal lipid metabolism?
Abnormal api-protein, receptors or lipoprotein lipase
What do genetic dyslipidaemias cause?
Fatty deposits in artery
