Lecture 5: Lipid metabolism - Breakdown Flashcards
(31 cards)
Give three roles of lipids.
- main form of stored energy
- Major component of cell membranes
- hormones
What is another name for a triglyceride?
Triacylgycerol
What is a triglyceride?
The main storage form of fat made up of 3 fatty acids in ester linkage to one glycerol molecule.
What is a fatty acid?
A long chain carboxylic acid
With respect to fatty acids, what do the terms saturated, mono-unsaturated and polyunsaturated mean?
Saturated - no C=C double bonds
Mono-unsaturated - one C=C double bond
Polyunsaturated - more than one C=C double bond
Explain the notation C18:0.
This means that the fatty acid being referenced has 18 carbon atoms and 0 C=C double bonds.
Give the lengths of fatty acid chain which are classified as a) short, b) medium, c) long and d) very long. Indicate which are the commonest and rarest lengths.
a) Fewer than 8 carbons
b) 8 - 14 carbons
c) 15 - 22 carbons (commonest)
d) More than 22 carbons (rarest)
Are fatty acids positively charged, negatively charged or neutral at physiological pH?
Negatively charged. (O=C-O-)
Give two examples of saturated fatty acids and one example of a mono-unsaturated fatty acid.
Saturated: palmitate (protonated form of palmitic acid)(C16:0) and stearate (C18:0)
Mono-unsaturated: Oleate (C18:1)
Where are triglycerides stored?
In adipose tissue (fat). Triglycerides form droplets and globules in cytoplasm of adipocytes (fat cells).
Why do we store fats?
- Fats are a much better store of energy than carbohydrates (fats are much more reduced than carbohydrates and are very non-polar so can be stored in a very dense anhydrous form)
- Stored glycogen will only last 12-24 hours, whereas stored fat can last about 12 weeks (without eating anything)
- Fats are the main energy source of all tissues except the brain, red blood cells and rapidly contracting muscles.
Give a general overview of the breakdown of lipids.
1) Mobilisation of free fatty acids from triglycerides in adipose tissue into blood
2) Free fatty acids transported in the blood to tissues by serum albumin (using its hydrophobic binding sites)
3) Free fatty acids activated by reaction with Coenzyme A
4) Transported into mitochondria (for long chain fatty acids this requires conjugation with a molecule called carnitine)
5) Beta-oxidation in matrix of mitochondria
6) Final oxidation of acetyl CoA in TCA cycle
What stimulates the mobilisation of fatty acids from triglycerides?
Glucagon or adrenaline
What happens when glucagon or adrenaline bind to their transmembrane receptor?
When glucagon/adrenaline binds to the transmembrane receptor, the attached G-protein exchanges its GDP for GTP, which moves along the membrane to activate adenylate cyclase. Adenylate cyclase converts ATP to cAMP, which activates cAMP-dependent protein kinase A. Protein kinase A then phosphorylates Triacylglycerol lipase, which hydrolyses the first fatty acid off the triacylglycerol, leaving a diacylglycerol. The diacylglycerol has its remaining two fatty acids removed by other lipases (through hydrolysis), releasing glycerol and free fatty acids.
Give 2 molecules which Coenzyme A is derived from.
ATP and pantothenic acid
What is pantothenic acid also known as?
Vitamin B5
Describe the activation process by Coenzyme A.
Step 1) The carboxylate ion of the fatty acid attack ATP and displaces the outer two phosphates, producing AMP with the fatty acid attached.
Step 2) The lone pair of electrons on the SH group of CoASH nucleophilically attacks the AMP-fatty acid, releasing AMP and producing a fatty acyl-CoA (a fatty acid attached to Coenzyme A)
This activation process uses the equivalent of 2 ATP molecules and requires the enzyme Acyl-CoA synthetase.
How are activated long chain fatty acids transported into the mitochondria?
The molecule carnitine (which is a zwitterion at physiological pH) displaces CoA in the fatty acid-CoA, releasing CoASH, via carnitine acyltransferase I.
What inhibits the displacement of CoA by carnitine?
Malonyl-CoA
Which membranes are carnitine acyltransferase I and carnitine acyltransferase II in?
Carnitine acyltransferase I is in the outer mitochondrial membrane and carnitine acyltransferase II is in the inner mitochondrial membrane.
What are the functions of carnitine acyltransferase I and carnitine acyltransferase II?
Carnitine acyltransferase I replaces CoA with carnitine, so that the fatty acid can get into the matrix from the inter-membrane space (Acyl CoA crosses the outer mitochondrial membrane through a pore).
Acyl-carnitine is then transported across the inner mitochondrial membrane into the matrix by a carrier protein.
In the matrix carnitine acyltransferase II removes carnitine from the fatty acid and replaces it with CoA.
Note: available data cannot determine whether carnitine is added inside or outside the mitochondria.
Describe the process of beta-oxidation.
The acyl CoA, which has now entered the matrix of the mitochondria, undergoes 4 reactions to release a molecule of acetyl CoA (2C). This cycle then repeats until the fatty acid is completely degraded.
The 4 reaction cycle is as follows:
1) Dehydrogenation: The acyl CoA is converted to an enoyl-CoA by Acyl-CoA dehydrogenase, with FAD being simultaneously being converted to FADH2.
2) Hydration: Enoyl-CoA is hydrolysed by 3-Hydroxyacyl-CoA by Enoyl-CoA hydrase (addition of water).
3) Dehydrogenation: 3-Hydroxyacyl-CoA is then converted to beta-Ketoacyl-CoA by 3-L-Hydroxyacyl-CoA dehydrogenase, with the simultaneous conversion of NAD+ to NADH + H+.
4) Thiolytic cleavage: Beta-ketoacyl-CoA is then converted to Acyl-CoA and acetyl CoA by thiolase, with the addition of CoA.
This acyl CoA then re-enters the start of the cycle, being converted to enoyl-CoA.
What is significant about the enzyme Acyl-CoA dehydrogenase?
It has 3 isozymes (enzymes which catalyse the same reactions with slightly different substrate specificity (here it is chain length)).
Which functional group is created in each step of the 4 reaction cycle of beta oxidation?
1) C=C double bond
2) Hydroxyl
3) Ketone
4) Thioester
