1.05 - Lipid Metabolism Flashcards by Lachlan Facey

What are lipids?

Waxy, greasy, oily constituents of the cell

A group of similar compounds

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What are the basic building blocks of all major lipid species?

Fatty acids and sterols

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Where are basic lipids derived?

Mainly from the diet but can also be synthesised

Cholesterol for example can be obtained from both

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What are the roles of Lipids?

Biomembrane structure
Bio-signalling
Energy

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Describe the structure and nomenclature of Fatty Acids

Composed of non-polar hydrocarbon chain and a polar carboxylic acids group
Carboxylic acid group is charged at a neutral pH
In humans, fatty acids have an even number of carbon atoms
Commonly lengths of 14, 16, 18 carbons
May have points of unsaturation (i.e. double bonds)

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Name some molecules that are lipids

Fatty Acids
Cholesterol
Triglycerides
Diglycerides
Phospholipids
Eicosanoids
Prostaglandins
Leukotriends
Steroid Hormones
Bile Acid/Salts

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What is the purpose of double/triple bonds in the fatty acid chain?

Give the chain a kink which is of structural importance

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Why is the beta carbon in a fatty acid chain of importance?

It is the site of beta-oxidation. It is the second carbon from the carboxylic acid carbon (terminal carbon).
The one next to this terminal carbon is the alpha
Terminal carbon –> alpha carbon –> beta carbon

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What is glycerol?

A three carbon alcohol that is major acceptor of fatty acids

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Describe the formation of Di- & Triglycerides

The carboxyl group of fatty acids is made more reactive by the addition of Coenzyme A –> Fatty Acyl CoA
Fatty Acyl CoA’s react with the alcohols on glycerol to generate:
- Diglycerides –> synthesis of phospholipids and signalling molecules
- Triglycerides –> storage and transport of FAs

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Describe the structure of phospholipids

Major constituent of biomembranes
Composed of fatty acids attached at Carbons 1&2 on glycerol
Phosphate and a head group (X) attach at the third carbon
- This X group can be a variety of molecules

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Describe the solubility of lipids

all types of lipids have poor aqueous solubility but are essential for cellular function and structure..
The ampiphilicity is a crucial element of solubility
- Polar elements contact an aqueous solvent (carboxylic acids are on the outside)
- Non-polar elements are shielded

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What are micelles and liposomes

Micelles - single layer (circular structure) of fats & detergents with polar heads on outside and hydrophobic tails on inside
Liposome - Spherical structure with bilayer of phospholipid.
Proteins may be accommodated in both

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Describe Lipoproteins

Lipid Transport Vehicles
A surface hemi-leaflet of phospholipids
Filled centrally with TAGs (80% of mass)
Apolipoproteins (APL) integrated in surface --> interact with receptors and activate lipases 
Cholesteryl-esters in core

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What is a lipase?

A lipase is an enzyme that catalyzes the hydrolysis of lipids. E.g. releases fatty acids from glycerol

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What are the forms of lipoproteins, in order of size?

Chylomicrons > Low density lipoprotein (LDL) > Very Low Density Lipoprotein (VLDL) > High Density Lipoprotein (HDL)

What is the role of the liver in lipid metabolism

Makes and stores fatty acids

Describe the mobilisation of Fat Stores

Adipose tissue stores fat
Adrenaline & Glucagon –> signal release of FAs
Signal transduction at Adipocytes
Hydrolysis of FAs from TAGs by lipase
FAs enter blood bound to serum albumin
Delivery of FAs to peripheral tissues for catabolism

Where is fat stored?

Adipose tissue

How is energy from FAs provided

Beta-Oxidation

Describe activation of FAs

Fatty acids are non-reactive so therefore required activation
Conjugation to Co-Enzyme-A (CoA or CoASH) - ATP driven
FA + CoA + ATP –> AMP + PPi + Acyl-CoA

Describe Entry of FAs into the Mitochondria

Carnitine Acyl Transferase (CAT)
CAT1: Takes the CoA off the Acyl-CoA and replaces it with a carnitine molecule –> Acyl-Carnitine
Carnitine Transferase (CT): Moves Acyl-Carnitine in to the mitochondria while also moving a molecule of Carnitine out of the inner mitochondrial membrane (Antiporter)
CAT2: Removes the carnitine from Acyl-Carnitine and replacing it with CoA reforming Acyl-CoA. The released carnitine is then able to be shuttled back out of the mitochondria by CT

Describe Beta-Oxidation

Occurs entirely in the mitochondrial matrix
The beta-carbon is oxidised
2 carbons liberated each cycle as Acetyl-Coa
New Acyl-CoA(n-2) rejoins the process
Also produces two reduced cofactors per cycle (FADH2 and NADH)

Where does Beta-Oxidation occur?

Mitochondrial Matrix

What is made during each cycle of Beta-Oxidation?

One Acetyl-CoA molecule One Acyl-CoA(n-2) FADH2 NADH

What is the significance of the production of Acetyl-CoA during beta oxidation?

It provides a link between beta-oxidation and the TCA cycle and Acetyl-CoA is an entry point in the TCA Cycle

What is the significance of the production of FADH2 and NADH during beta-oxidation?

These can enter the TCA cycle for further oxidation

What are the four main chemical steps in beta-oxidation

1. Oxidation of Beta carbon (CH2-CH2 --> CH--CH). FAD--> FADH2 2. Hydration (CH--CH +H20 --> C(OH)H-CH2) 3. Oxidation (C(OH)H-CH2 --> C(O)-CH2) 4. Thiolation (C(O)-CH2 + CoASH --> Acetyl CoA + AcylCoA(n-2)

Describe beta-oxidation in unsaturated FAs

Beta-oxidation continues as normal until the double bond becomes an issue Enoyl-CoA isomerase reorientates the double bond Beta oxidation continues

Describe beta oxidation of long chain FAs

Fatty acids with 20 or more carbons are poor substrates for beta oxidation Occurs in peroxisome instead Not coupled to ATP synthesis

Describe beta oxidation of odd chain FAs

Beta oxidation proceeds as normal Final product is propionyl-CoA (3-carbon) Propionyl-CoA is converted to succinyl-Coa (TCA intermediate)

Describe the regulation of fat catabolism via supply

Cellular utilization of fatty acids is dependent on supply Mobilisation occurs from adipose tissue Mobilisation dependent on hormone sensitive lipase

Describe the intracellular regulation of fat catabolism

Futile cycles within cells are discouraged! Beta-oxidation and fatty acid synthesis cannot occur simultaneously Malonyl-CoA is the starting point for synthesis Malonyl-CoA is located in the cytoplasm Malonyl-CoA inhibits CAT-1 - Inhibition of CAT-1 prevents supply of fatty acid to beta-oxidation