Lipid synthesis and degradation Flashcards
How are fats obtained
Mainly from de novo from carbohydrates but also from diet
What do lipids do
They play an essential role in
- Membranes
- Uptake of lipid soluble vitamins
- Precursor of steroid hormones
- Energy store
What are different types of fats
- Fatty acids
- Triglycerides or neutral fats
- Cholesterol
Which tissues prefer fats as their energy source
Tissues such as cardiac muscle
What stores and what synthesises lipids
Stored in adipose tissue
Synthesised in the liver
What is the major product of fatty acid synthesis
Palmitic acid (16 carbon molecule)
How is compartmentalisation taking place
Synthesis occurs in the cytosol but breakdown occurs in the mitochondria, absolute separation
What does lipid synthesis require
Acetyl-CoA, NADPH and ATP
What is the first step of lipid synthesis
Acetyl-CoA (2C) + ATP + HCO3- is made into malonyl-CoA (3C) + ADP + Pi
What does the first step of lipid synthesis require
Vitamin biotin and acetyl-CoA carboxylase
What is the first step of lipid synthesis regulated by
Activated by citrate and inhibited by palmitic acid
What is the second step of lipid synthesis
- Reaction with ACP (acyl carrier protein) to produce malonyl-ACP (C3)
- Condensation reaction with Acetyl-ACP (C2) plus decarboxylation to form acetoactyl-ACP (C4)
- Reduction, dehydration and reduction to form butyryl-ACP (C4)
- Combines with malonyl-ACP (3C) and undergoes decarboxylation to create C6 molecule
Fatty acid synthase
Exists as a dimer so that the synthesis is as efficient as it can be
Products enters the complex and binds to the enzyme, and its passed along the active sites, the last one adds the 2 carbons, and it then moves to the other side of the dimer
What is cholesterol
A rigid hydrophobic molecule virtually insoluble in water
Its a precursor of sterols, steroids and bile salts
How is it transported
Transported in circulation as cholesteryl esters
What is it used for and why
Its important in membrane components
It cannot be oxidised to O2 and H20 therefore it cannot provide any energy
Where is cholesterol synthesised
In the ER
What is the major regulatory step in cholesterol synthesis and why
Conversion of 3-hydroxyl-3-methlglutaryl CoA (HMGCoA) to mevalonate
Cholesterol inhibits HMGCoA reductase
What are the steps in the degradation of fatty acid and where do they occur
- Mobilisation of fat stores, mainly triglycerides occurs in adipocytes
- Activation of triglyceride and transport to mitochondria occurs in liver cytosol
- Degradation occurs in liver mitochondrion
What happens in the mobilisation of fat stores
- cAMP will activate protein kinase
- Protein kinase activates and phosphorylates triacyglycerol lipase
- This makes triacyglycerol into diacylglycerol
- This is made into free fatty acids and glycerol by other lipases
- The free fatty acids will leave the cell
- Glucagon and adrenaline are involved in this mobilisation
What is the fate of glycerol
Its absorbed by the liver as its the only part of the triglyceride that can be used to make glucose
How is glycerol processed
- First its phosphorylated to glycerol-3-phosphate
- This is then oxidised to dihydroxyacetone phosphate
- This is isomerised to glyceraldehyde-3-phosphate
- This is either used in glycolysis or gluconeogenesis which is used to maintain blood glucose
How are the free fatty acids activated and transported to the mitochondria
- Fatty acids are transported to the liver by acyl-CoA synthase in the cytoplasm
- The acyl-CoA reacts and oxidises carnitine, producing acyl carnitine
- Acyl carnitine can pass through translocase into the matrix of mitochondria
- CoA is oxidised forming Acyl-CoA and carnitine again
How is this transport regulated and why
Malonyl-CoA inhibits transport since the cell the cell is storing energy when there is excess glucose present
What is carnitine deficiency
Causes muscle weakness or even death
What happens in lipid degradation
Acyl-CoA is degraded by sequential removal of 2 carbon units
FADH2, NADH and acetyl-CoA is made
What is ketogenesis
Acetyl-CoA is converted into acetoactyl-CoA
This is converted to HMG-CoA
This is made into acetoacetate
This is reduced to 3-beta-hydroxybuterate or non-enzymically to acetone
What happens to ketone bodies
Its a major source for cardiac muscle and the renal cortex
During starvation up to 75% of the brains energy is derived from acetoacetate
