Lipid synthesis and degradation Flashcards
How is fat obtained?
Obtained either from diet or made de novo from carbohydrates
What role does fat play in biological functions?
○ Membranes
○ Uptake of lipid soluble vitamins
As precursors of steroid hormones
What is the relation between one gram of fat and either carbohydrate or protein?
Energy from one gram of fat = over twice that of either carbohydrate or protein
How much energy from 1 g of fat?
37KJ
How much energy from 1 g of protein?
17KJ
How much energy from 1 g of carbohydrate?
16KJ
What happens when calorific intake exceeds consumption?
When calorific intake exceeds consumption excess is laid down as fat
Where are fatty acids usually synthesised and stored?
Usually synthesised in liver however stored in adipose tissue
What do cardiac muscle use as their preferred energy source?
Cardiac muscle use fat as preferred energy source
What is the most common source of metabolic building blocks?
○ Dietary carbohydrate is the most common source of metabolic building blocks although some amino acids can also be used
What is the major product in fatty acid synthesis?
Palmitic acid is the major product that is modified by enzymes to produce different fatty acids
What is the structure of a fatty acid?
Chains of methyl groups with terminal carboxyl group
Do fatty acids have double bonds?
Can have double bonds and if present, usually in cis conformation
What are humans unable to create regarding double bonds?
Humans unable to create double bonds less than position 9
Where are essential fatty acids obtained from?
• Essential fatty acids obtained from diet
Where does fatty acid synthesis from glucose occur?
Occurs in cytosol
What happens to some citrate in fatty acid synthesis?
• Some citrate exported out the mitochondria and converted into acetyl CoA
○ Acetyl CoA cannot cross membrane whereas citrate can
What is acetyl CoA converted into and what happens to it?
• Acetyl CoA converted to fatty acids:
○ Some stay in liver
○ Majority imported as free
fatty acids and
consumed in non-hepatic
tissue
Majority stored in
adipocytes(have ability to
synthesise fats)How is acetyl CoA transferred into the cytosol?
- Pyruvate enters mitochondria and converted to oxaloacetate
- Oxaloacetate combines with Acetyl CoA to form citrate
- Citrate transported out and cleaved to form acetyl CoA and oxaloacetate
- Oxaloacetate is converted to malate and then pyruvate
Acetyl CoA and NADPH formed
What activates the first step in citrate malate antiport?
Activated by citrate
What is the citrate-malate antiport inhibited by?
Inhibited by palmitic acid
What vitamin is required for the citrate-malate antiport first step?
Vitamin Biotin
What type of step is the first step in citrate-malate antiport?
Irreversible regulatory step
What is acetyl CoA carboxylase inhibited by?
Inhibited by phosphorylation
When is the expression of acetyl CoA carboxylase increased?
Expression of Acetyl CoA carboxylase increased by high carbohydrate and low fat
When is the expression of acetyl CoA carboxylase decreased?
Expression of Acetyl CoA carboxylase decreased by low carbohydrate and high fat
Where does the second step of the citrate-malate antiport occur?
Occurs in the cytosol
What does elongation mean in terms of the second step in the citrate-malate antiport?
Means the addition of 2C
What occurs in the second step of the citrate-malate antiport?
a. Malonyl CoA formed by acetyl CoA carboxylase
i. Malonyl residue transferred to ACP
b. A second acetyl molecule from Acetyl CoA is then transferred to ACP where two condense to form Acetoacytyl-ACP
c. Fatty acid synthase is a multi-enzyme complex required for fatty acid synthesis
Exists as a dimer to make synthesis efficient as possible
What is the structure of cholesterol?
Rigid hydrophobic molecule
Virtually insoluble
What is cholesterol a precursor of?
Precursor of steroids, sterols and bile salts
As what is cholesterol transported as?
Transported in the circulation as cholesteryl esters
Why is cholesterol unable to provide energy?
Cannot be oxidised to O2 and H20 so provide no energy
Why is cholesterol an important membrane component?
Important membrane component for fluidity
Where is cholesterol mostly synthesised?
Mostly synthesised in the ER
What does cholesterol synthesis start with?
Starts with activation of acetate, acetyl CoA
What is the major regulatory step?
Major regulatory step is the conversion of 3-hydroxyl-3-methylglutaryl CoA to mevalonate
What does cholesterol inhibit and what is that involved in?
• Cholesterol inhibits HMGCoA reductase
Enzyme involved in its own synthesis
Why is it difficult to reduce circulating cholesterol by diet alone?
Difficult to reduce circulating cholesterol by diet alone as endogenous synthesis is increased
In the first step of fatty acid degradation(Mobilisation adipocyte), what does cAMP activate and what is the activated molecule involved in?
cAMP activates protein kinase A which is involved in the breakdown of glycogen and inhibition of glycogen synthesis
What does the activated protein kinase A do in mobilisation adipocyte?
Activated protein kinase A will phosphorylate and activate triacylglycerol lipase, removing fatty acid from glycerol
What breaks down triaglycerol and what is formed?
Phosphorylated triacylglycerol lipase breaks down triacylglycerol to form diacylglycerol and transported via lipoproteins or bound to albumin.
What component goes back to the liver?
One of the components, glycerol, get back to the liver as its the only part of the fatty acid which can be used to make glucose
Where are fatty acids transported and what are they activated by?
Fatty acids transported to liver and activated by acyl-CoA synthase in the cytoplasm
What happens to the acetyl CoA which is produced?
Acetyl CoA produced is transported across the inner mitochondrial membrane bound to the alcohol carnitine
In the second step of fatty acid degradation(activation), where does it occur?
Occurs in the liver cytosol
How are the fatty acids activated?
FA activated by reacting with CoA requiring ATP
Where are the fatty acids transported using what and for what purpose?
Transported to inner mitochondrial matrix for oxidation using carnitine
What inhibits the transport of fatty acids?
Transport inhibited by malonyl-CoA
What does it mean therefore if there is a large amount of malonyl CoA?
i. So large amounts of malonyl CoA prevents breakdown when excess glucose is present
In the third step of fatty acid degradation(degradation), what is Acyl-CoA degraded by
Degraded by sequential removal of 2C units
As a result of the degradation of acyl-CoA, what is produced?
FADH2, NADH and acetyl-CoA
What are used for glycolysis from the products formed from the degradation of acyl-CoA?
FADH2 and NADH
What forms ATP in fatty acid oxidation(Beta-oxidation)?
FADH2 and NADH
When does acetyl CoA only enter the citric acid cycle?
Only in the presence of glycolysis
How many ATP molecules do we get from the complete oxidation of palmitic acid?
106 molecules of ATP
What type of chain yield is in last round of oxidation?
Odd chain length yield propionyl-CoA in the last round of oxidation
How are odd numbered double bonds removed?
Removed by isomerase
How are even numbered bonds removed?
Even numbered bonds removed by reductase and isomerase
What is acetyl CoA in hepatocytes converted into and transported where?
Acetly-CoA in hepatocytes converted to ketone bodies and are transported to non hepatic tissue for metabolism
In ketogenisis, what is acetyl CoA converted into?
Acetyl-CoA converted to acetoacetyl-CoA
What is acetoacetyl -CoA converted into?
Converted to HMG-CoA
What is HMG-CoA converted into?
Converted to acetoacetate
What can acetoacetate be reduced to?
Acetoacetate can be reduced to 3-β-hydroxybuterate or non-enzymatically to acetone
When is the rate of ketogenisis high and why?
Ketogenisis high when ration of insulin/glucagon is low as this inhibits acetly-CoA carboxylase
What are ketones a major energy source for?
Major energy source for cardiac muscle and renal cortex
How does insulin regulate fat metabolism?
○ Increases glycolysis in the liver
○ Increases fatty acid synthesis in the liver
○ Increases triglyceride in adipose tissue
Decreases β-oxidation
How does glucagon regulate fat metabolism?
Glucagon increases triglyceride mobilisation
What happens during starvation?
During starvation up to 75% of the brains energy is derived from acetoacetate.
