Essential Fatty Acids, TAG Metabolism and the Carnitine Shuttle. Flashcards
What 2 factors about fatty acids will lead to an increase in melting point?
Chain length.
Degree of unsaturation (double bonds).
How many carbons and double bonds does palmitate have and what is its melting point?
16 carbons.
No double bonds.
63C.
How many carbons and double bonds does stearate have and what is its melting point?
18 carbons.
No double bonds.
70C.
How many carbons and double bonds does oleic acid have and what is its melting point?
18 carbons.
1 double bond.
13C.
How many carbons and double bonds does linoleic acid have and what is its melting point?
18 carbons.
2 double bonds.
-9C.
How many carbons and double bonds does alpha lonoleic acid have and what is its melting point?
18 carbons.
3 double bonds.
-17C.
How many carbons and double bonds does arachidonic acid have and what is its melting point?
20 carbons.
4 double bond.
-50C.
How many carbons and double bonds does EPA have and what is its melting point?
20 carbons.
5 double bonds.
-54C.
How many carbons and double bonds does DHA have and what is its melting point?
20 carbons.
6 double bond.
-45 to -50C.
What lipids are usually found at position 1 on the glycerol backbone in phospholipids?
Palmitate and stearate.
What is formed when animals introduce a double bond into palmitate and stearate?
Palmitoleate and oleate.
What end of a fatty acid will carbon 1 be at?
The carboxyl end.
Where can animals introduce double bonds in fatty acids?
9 carbons away from the carboxyl end.
What carbons is the double bond placed at when palmitoleate and oleate are formed?
Between carbons 9 and 10.
This is written as Δ9.
Can animals place double bonds in fatty acids near the methyl end?
No, only 9 carbons away from the carboxyl end.
What kind of double bonds will always be formed by animals?
Cis double bonds.
How can animals obtain fatty acids with bonds beyond Δ9?
From the diet.
What are essential fatty acids?
Fatty acids with bonds beyond Δ9 that are obtained in the diet.
What organisms form essential fatty acids?
Plants.
Can animals alter essential fatty acids?
They can elongate them but they cannot change the location of the double bond.
How can animals form bonds that are beyond carbon 9 in an essential fatty acid?
By elongating the fatty acid.
They can never move the bond.
How is the family of an essential fatty acid is determined?
By counting backwards from the methyl end until the 1st double bond is reached.
The methyl end of an essential fatty acid is known as what carbon?
The ω carbon.
What determines the family of an essential fatty acid?
The number of carbons between the methyl end and the 1st double bond will determine the family.
What family of essential fatty acid is linoleic acid?
Omega-6.
What family of essential fatty acid is α linolenic acid
Omega-3.
At what end will carbons be added when animals are elongating an essential fatty acid?
To the carboxyl end.
Why does the family of essential fatty acid not change after elongation?
Because the number of carbons between the methyl end and the 1st double bond does not change.
Can animals introduce any double bonds into an essential fatty acid?
They can introduce double bonds between the carboxyl end and Δ9.
If animals introduce double bods to an EFA will it change the family?
No because animals introduce them at the carboxyl end and not at the methyl end.
Arachidonic acid is what family of EFA?
Omega 6.
Linoleic acid is elongated to form what fatty acid in humans?
Arachidonic acid.
What will humans use arachidonic acid for?
To make eicosanoids.
How many carbons do eicosanoids have?
20 carbons.
Where do we get omega 3 fatty acids from?
From fish who get them from the consumption of algae.
How do fish store alpha linolenic acids?
As eicosapentaenoic acid, 20:5, (EPA).
How do humans alter EPA when they obtain it from fish?
They elongate it to docosahexaenoic acid, 22:6, (DHA).
Where is DHA usually found?
In phospholipids in the brain.
DHA is important for what in humans?
Brain and retina function.
It will protect against heart disease.
Why are TAGs synthesised?
To store free fatty acids so that they do not damage cells
What is the structure of a TAG?
A glycerol backbone that is bound to 3 fatty acids.
What group is removed from fatty acids when they are placed into TAGs?
The hydroxyl group.
What is the common intermediate that is formed during TAG synthesis?
Phosphatidic acid.
How is phosphatidic acid formed?
When a glycerol 3-phosphate molecule from glycolysis is combined with 2 fatty acyl CoAs.
What can phosphatidic acid be used to form?
Phospholipids, DAGs and TAGs.
Where does TAG synthesis occur?
In the liver, intestinal mucosal and fat cells.
When does the liver synthesise TAGs?
When blood sugar levels are high.
What happens to TAGs that are synthesised in the liver?
They are placed inside a VLDL transport protein and released into the blood to be delivered to fat cells.
What does VLDL stand for?
Very low density lipoprotein.
What hormone activates TAG synthesis in the liver?
Insulin.
When are TAGs synthesised in the intestinal mucosal cells?
When the intestinal mucosal cells will join a MAG to 2 free fatty acids to form a TAG.
TAGs formed in the intestinal mucosal cells are transported in what transport molecule?
A chylomicron.
When is insulin present in the body?
When blood glucose levels are high.
Will the TAGs that are stored in adipose tissue ever leave the fat cell?
No.
Why will TAGs be degraded?
To provide energy for the body when glucose levels are low.
When will TAGs be degraded?
During fasting and in fight or flight scenarios.
What enzyme degrades TAGs?
Hormone sensitive lipase.
When is HSL active?
When it is phosphorylated.
What activates the phosphorylation of HSL?
Epinephrine or low levels of insulin.
What is formed when TAGs are broken down?
3 free fatty acids and glycerol.
What parts of a TAG are used for energy?
The fatty acids.
What happens to glycerol when it is released from a TAG?
It is recycled or excreted.
What is the difference in site of synthesis for hormone sensitive lipase and pancreatic lipase?
Hormone sensitive lipase = Fat cells.
Pancreatic lipase = Pancreatic cells.
What is the difference in site of action for hormone sensitive lipase and pancreatic lipase?
Hormone sensitive lipase = Fat cells.
Pancreatic lipase = Lumen of small intestine.
What is the difference in mode of action for hormone sensitive lipase and pancreatic lipase?
Hormone sensitive lipase = Cleaves TAGs to 3 free fatty acids and glycerol.
Pancreatic lipase = Cleaves TAGs to MAGs and 2 free fatty acids.
What is the difference in mode of activation for hormone sensitive lipase and pancreatic lipase?
Hormone sensitive lipase = Phosphorylation, low insulin levels, epinephrine and high cortisol.
Pancreatic lipase = Conjugated bile salts and procolipase.
Cleaved fatty acids will bound to what in the blood?
They will be non-covalently bound to albumin.
Where are cleaved fatty acids transported to once they are in the bloodstream?
To the liver and other tissues.
What happens when cleaved fatty acids arrive at cells from the bloodstream?
They will be taken up for beta oxidation.
What happens to glycerol that is formed by TAG cleavage during fasting?
It will be used by an enzyme to make glycerol 3-phosphate that can be used in gluconeogenesis.
What enzyme converts cleaved glycerol to glycerol 3-phosphate in the fasting state?
Glycerol kinase.
Can gluconeogenesis and beta oxidation occur at the same time?
Yes.
What gives the liver enough energy to carry out gluconeogenesis?
The beta oxidation of fatty acids.
NADH.
ACoA.
What is the hearts preferred fuel?
Fatty acids.
What is done to reduce the detergent characteristics of fatty acids before they are released to give energy to cells?
They are converted to fatty acyl CoA and then esterified.
What enzyme will activate and esterify free fatty acids?
Fatty acyl CoA synthase.
What will fatty acyl CoA synthase use as its substrates?
A free fatty acid.
ACoA.
ATP.
Where will fatty acyl CoA synthase activate and esterify free fatty acids?
In the outer mitochondrial membrane.
Is the reaction that is catalysed by fatty acyl CoA synthase reversible?
No.
It is irreversible.
Why is the activation and esterification of fatty acids irreversible?
So that free fatty acids cannot be randomly formed as they would damage the cell.
The activation and esterification depends on the availability of what molecule?
CoA.
Where does the CoA used for fatty acid activation come from?
The rapid turnover of activated fatty acids mean that CoA can be recycled and re-used for fatty acid activation.
What happens to fatty acyl CoA molecules?
They can be used for energy.
To create phospholipids or sphingolipids.
They can be re-syntheised as TAGs.
What happens when fatty acyl CoA reaches adipose tissue or a cell membrane?
They can be esterified and the CoA can be removed and recycled.
Can long chain fatty acids enter the inner mitochondrial membrane?
No.
Where does the beta oxidation of fatty acids occur?
In the mitochondrial matrix.
What fatty acids can cross the inner mitochondrial membrane?
Medium and short chain fatty acids.
What is the carnitine shuttle used for?
To transport long chain fatty acids across the inner mitochondrial membrane.
What organ is the carnitine shuttle particularly important in?
The heart.
What fatty acid is used to power the heart?
Palmitoyl CoA.
The oxidation of Palmitoyl CoA will generate how much ATP?
131 ATP.
How will the heart gain TAGs after a meal?
From TAGs that are found in lipoproteins.
How will the heart gain TAGs in the fasting state?
From the breakdown of TAGs in fat cells.
What will the liver use as an energy source during fasting?
Only fatty acid oxidation.
The NADH and ACoA that are produced in the beta oxidation of fats will are used by the liver for what?
As allosteric regulators of gluconeogenesis.
What happens if the carnitine shuttle in the liver is inhibited?
It will result in severe hyperglycaemia.
What happens in step 1 of the carnitine shuttle?
Fatty acyl CoAs cross into the intermembranous space and are joined to a carnitine molecule to make fatty acylcarnitine and free CoA.
Where are fatty ACoAs synthesised?
In the outer membrane of the mitochondria.
What enzyme joins fatty acyl CoA and carnitine in the intermembranous space?
Carnitine palmitoyl transferase-1.
Where is carnitine palmitoyl transferase-1 found?
In the intermembranous space bound to the outer membrane.
What is the susbtrate of carnitine palmitoyl transferase-1 found?
Fatty acyl CoA and carnitine.
What is the product of carnitine palmitoyl transferase-1 found?
Fatty acylcarnitine and free CoA.
What happens in step 2 of the carnitine shuttle?
A translocase enzyme takes fatty acylcarnitine across the inner mitochondrial membrane and delivers it into the mitochondrial matrix.
What is the translocase enzyme in step 2 of the carnitine shuttle called?
Carnitine acyl carnitine translocase.
How is free carnitine removed from the matrix?
As carnitine acyl carnitine translocase returns to the inter-membranous space it will transport free carnitine out of the matrix.
What does carnitine acyl carnitine translocase do?
It transports free carnitine into the inter membranous space.
What happens in step 3 of the carnitine shuttle?
An enzyme uses CoA to form fatty acyl CoA and free carnitine.
What enzyme is used in step 3 of the carnitine shuttle to form fatty acyl carnitine and free CoA in the mitochondrial matrix?
Carnitine palmitoyl transferase 2 (CPT-2).
What will fatty acyl CoA used for when it is in the mitochondrial matrix?
Beta oxidation.
What is the substrate for CPT-7?
Fatty acylcarnitine and free CoA.
What is the product for CPT-7?
Fatty acyl CoA and free carnitine.
What must be inhibited when fatty acids are being synthesised?
The carnitine shuttle.
What will inhibit the carnitine shuttle?
The presence of manolyl CoA in the cytosol.
The presence of manolyl CoA in the cytosol will lead to what?
Fatty acid synthesis.
