Sean - Fatty Acid Catabolism Flashcards
What are lipids?
(5)
Group of chemically diverse, naturally occurring molecules
Macromolecules
Hydrophobic molecules
Compartmentalised molecules (in vivo)
Bound to hydrophilic molecules (in vivo)
What are the three main functions of lipids?
Cell structure
Energy storage
Intracellular messengers
In vivo lipids are compartmentalised, what does this mean?
They are membrane associated
In vivo lipids are bound to hydrophilic molecules, give an example of such a case.
Lipoproteins
Where are phospholipids often found?
Often found in structure
Where are glycolipids found and what is their main function?
(3)
They are lipids with a carbohydrate attached
They are used in cell signalling
They are found on the surface of cells to relay messages
What does saturated mean?
No double bonds
What does unsaturated mean?
There is at least one double bond
What does monounsaturated mean?
There is one double bond
What does polyunsaturated mean?
More than one double bond
How do you go about naming a fatty acid?
Count the number of carbons
Count the number of double bonds
Delta designates the position of the first C atom involved in the double bond
e.g. 16:1 (delta 9)
Classify unsaturated fatty acids
Cis and Trans fatty acids
What are trans fatty acids?
(4)
Synthetically produced unsaturated fatty aids
Produced by fermentation in the rumen of dairy animals
Hs are located on the opposite sides of the double bond
They pack in an orderly way to produce solid fats
What are Cis fatty acids?
(5)
Unsaturated fatty acids
Hs are on the same side of the double bond
Creates a kink or bend in the chain
Nearly all naturally occurring unsaturated fatty acids have this conformation
Do not contribute to the build up of cholesterol -> increase of LDL
Why do trans fatty acids increase risk of cardiovascular disease but not cis fatty acids?
Trans can pack in an organised fashion while cis cannot due to the ‘kink’ they produce in their carbon chain
Explain the risk associated with saturated fats and cardiovascular disease
Saturated fats lead to the increase of LDL (bad cholesterol) and increase in HDL (good cholesterol)
Give a source of saturated fat
Partially hydrogenated vegetable oils
How do mammals store fatty acids?
Triacylglycerols
Describe the structure of a triacylglycerol.
3 fatty acids linked to a glycerol (3C) by ester bonds
What is the main function of triacylglycerols?
Storage
What are the principle short term source of energy in humans?
Carbhydrates
What are the principle short term source of energy in humans?
Carbohydrates
What happens to excess glucose in the body?
It is converted into glycogen and stored in the liver
How much glycogen do humans store?
Only enough for a single day of energy
What happens to glycogen when glucose is needed?
Glycogen is broken down into glucose
What is the energy from tracylglycerols used for?
It’s used to sustain cellular activity
What are the three main sources of fatty acids?
They can be synthesised in one type of cell and can be transported to another
They can be consumed in the diet -> these are digested and degraded for energy/stored as triacylglycerols (exogenous reaction)
They can be stored as triacylglycerols in lipid droplets in adipocytes in adipose tissue (endogenous reaction)
Lipids are water insoluble but must be transported around the body, how is this done?
They are carried in blood plasma attached to proteins (lipoproteins)
These lipoproteins express signalling proteins so they can interact and coordinate with each other
What do lipoproteins consist of?
(5)
Apolipoproteins
Phospholipids
Cholesterol
Cholesteryl esters
Triacylglycerols
What are apolipoproteins?
A specific type of carrier proteins
How are lipoproteins classified?
Based on their density
What are the five main classifications of lipoproteins?
Chylomicrons
Very Low Density Lipoproteins (VLDL)
Intermediate Density Lipoproteins (IDL)
Low Density Lipoproteins (LDL)
High Density Lipoproteins (HDL)
What proteins is responsible for transporting fatty acids?
Albumin
Write a note on albumin.
(3)
Synthesised in the liver
Makes up half of all proteins in the blood
Binds up to 20 fatty acids
How does albumin transport fatty acids?
Up to 10 fatty acids bind to albumin
At target tissues these fatty acids dissociate from albumin
They then move across specific transporters in the plasma membrane into cells -> fuel
What is the first step in the processing of dietary lipids?
(2)
Bile salts emulsify dietary fats in the small intestine
Forming mixed miscelles
What is the second step in the processing of dietary lipids?
Intestinal lipases degrade triacylglycerols
What is the third step in the processing of dietary lipids?
Fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols
What is the fourth step in the processing of dietary lipids?
Triacylglycerols are incorporated with cholesterol and apolipoproteins into chylomicrons
What forms chylomicrons?
Triacylglycerols incorporated with cholesterol and apolipoproteins
What is the fifth step of the breakdown of dietary lipids?
Chylomicrons move through the lymphatic system and bloostream to tissues
What is the sixth step in the digestion of dietary fatty acids?
Lipoprotein lipase is activated by apoC-II in the capillary
This converts triacylglycerols to fatty acids and glycerol
What activates lipoprotein lipase?
ApoC-II
What does lipoprotein lipase do?
Converts triacylglycerols to fatty acids and glycerol
What is the seventh step in the breakdown of dietary fatty acids?
Fatty acids enter the cells
What is the eight step in the breakdown of dietary fatty acids?
Fatty acids are oxidised as fuel or reesterified for storage
What are chylomicrons?
A droplet of fat present in the blood or lymph after absorption from the small intestine
Describe the structure of a fat droplet
(4)
Triacylglycerols are stored within
A monolayer of amphiphatic phospholipids surrounds the droplet
Perilipins (proteins) protect the surface of the droplet
Perilipins restrict lipase access to the lipid droplets (prevents unnecessary release of fatty acids)
What signals the release of fatty acids?
Hormones such as glucagon and adrenaline
What causes signals for the release of fatty acids to be initiated?
The need for metabolic fuel
The fatty acids are then released and transported from adipose tissue to the energy requiring tissue
What is the first step in the release of fatty acids from triacylglycerols?
(3)
Blood glucose concentration falls
Glucagon is released
Glucagon binds its receptor to the adipocyte membrane
What is the second step in the release of fatty acids from triacylglycerols?
Glucagon has bound it’s receptor to the adipocyte membrane.
This binding stimulates adenylyl cyclase to produce cAMP
What does adenylyl cylase produce?
cAMP
What produces cAMP?
Adenylyl/adenyl cylase
What does adenylyl cyclase produce?
cAMP
What is the third step in the release of fatty acids from triacylglycerols?
cAMP has just been produced
(2)
cAMP activates PKA
PKA phosphorylates the hormone-sensitive lipase and perilipin molecules on the surface of the lipid droplet
What does cAMP activate?
PKA
What does PKA do?
It phosphorylates lipase and perilipin molecules on the surface of the lipid droplet
What is the fourth step in the release of fatty acids from triacylglycerols?
(2)
Perilipin is activated/phosphorylation
This permits lipase access to the surface of the lipid droplet
What is the fifth step in the release of fatty acids from triacylglycerols?
Lipase has just gotten access to the surface of the lipid droplet
Lipase hydrolyses triacylglycerols to free fatty acids
What is the sixth step in the release of fatty acids from triacylglycerols?
(3)
Triacylglycerol has just been hydrolysed by lipase
Fatty acids leave the adipocyte
They then bind to serum albumin in the blood
They are then carried in the blood
What is the seventh step in the release of fatty acids from triacylglycerols?
Fatty acids have bound to albumin and are being transported in blood
(3)
The fatty acids are released from the albumin
They enter a cell where energy is needed
They enter through a specific fatty acid transporter
What is the eight step in the release of fatty acids from triacylglycerols?
The fatty acids have just entered a cell in need of energy
The fatty acids are broken down in a process called B-oxidation
Where does B oxidation take place?
Mitochondria
What are the three stages to fatty acid utilisation in cells?
Activation
Transport
B oxidation
What happens during fatty acid activation?
Fatty acids are converted into fatty acyl-coenzyme A
What happens during fatty acid transport?
Import of the fatty acyl-coenzyme A into mitochondria
What happens during B-oxidation of fatty acids?
The conversion of a fatty acyl-coenzyme A into acetyl-CoA with the release of energy
What catalyses the activation of fatty acids?
Acyl-CoA synthase
Write a note on the activation of fatty acids. (Step 1 of utilisation of fatty acids)
(6)
Acyl-CoA synthase catalyses the formation of a thioester bond between the carboxyl group of the fatty acid and sulphydryl group (-SH) of coenzyme A
This generates a high energy fatty acyl-coenzyme A (CoA)
Acyl-CoA then goes through one of two pathways:
- transported into mitochondria and oxidised to release energy
- used in the cytosol to generate membrane lipids
Both reactions are driven by ATP hydrolysis in a coupled reaction
Write a note on the transport of fatty acyl-CoA into the mitochondria
(Phase 2 of the utilisation of fatty acids by cells)
(4)
Fatty acyl-CoA molecules forms on the cytosolic side of the outer mitochondrial membrane
There are no specific transporters present here to transport the molecules
Instead they use ‘the carnitine shuttle’
The fatty Co A molecules attach to carnitine and move through the carnitine transporter present on inner mitochondrial membranes
The OH group of carnitine interacts with the C=O group of the fatty acyl Co A
Coenzyme A is released and a fatty acyl-carnitine forms (catalysed by carnitine acyltransferase I/CAT I)
A transport protein present on the inner mitochondrial membrane allows cytosolic fatty acyl-carnitine to be swapped for mitochondrial carnitine (Fatty acyl-carnitine now present in the mitochondrial matrix)
Carnitine acyltransferase II (CATII) found on the inner mitochondrial membrane catalyses the conversion of fatty acyl-carnitine to fatty acyl-CoA (reverse affect of CAT I
Carnitine released is then recycled by exchange back to the cytosol
Fatty acid B-oxidation then occurs in the mitochondrial matrix
What catalyses the release of Coenzyme A from acetyl CoA to form fatty acyl-carnitine?
Carnitine acyltransferase I (CATI)
How does fatty acyl-carnitine get into the mitochondrial matrix?
A transport protein present on the inner mitochondrial membrane allows cytosolic fatty acyl-carnitine to be swapped for mitochondrial carnitine (Fatty acyl-carnitine now present in the mitochondrial matrix)
What does CAT I and II stand for?
Carnitine acyltransferase I and II
What does CAT II do?
(2)
Carnitine acyltransferase II (CATII) catalyses the conversion of fatty acyl-carnitine to fatty acyl-CoA
It’s the reverse affect of CAT I
Where is CAT II found?
Found on the inner mitochondrial membrane