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Biochemistry > 1.05 - Lipid Metabolism > Flashcards

1.05 - Lipid Metabolism Flashcards

1
Q

What are lipids?

A

Waxy, greasy, oily constituents of the cell

A group of similar compounds

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2
Q

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

A

Fatty acids and sterols

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3
Q

Where are basic lipids derived?

A

Mainly from the diet but can also be synthesised

Cholesterol for example can be obtained from both

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4
Q

What are the roles of Lipids?

A

Biomembrane structure
Bio-signalling
Energy

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5
Q

Describe the structure and nomenclature of Fatty Acids

A

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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6
Q

Name some molecules that are lipids

A 
Fatty Acids
Cholesterol
Triglycerides
Diglycerides
Phospholipids
Eicosanoids
Prostaglandins
Leukotriends
Steroid Hormones
Bile Acid/Salts
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7
Q

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

A

Give the chain a kink which is of structural importance

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8
Q

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

A

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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9
Q

What is glycerol?

A

A three carbon alcohol that is major acceptor of fatty acids

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10
Q

Describe the formation of Di- & Triglycerides

A

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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11
Q

Describe the structure of phospholipids

A

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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12
Q

Describe the solubility of lipids

A

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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13
Q

What are micelles and liposomes

A

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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14
Q

Describe Lipoproteins

A 
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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15
Q

What is a lipase?

A

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

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16
Q

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

A

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

17
Q

What is the role of the liver in lipid metabolism

A

Makes and stores fatty acids

18
Q

Describe the mobilisation of Fat Stores

A

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

19
Q

Where is fat stored?

A

Adipose tissue

20
Q

How is energy from FAs provided

A

Beta-Oxidation

21
Q

Describe activation of FAs

A

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

22
Q

Describe Entry of FAs into the Mitochondria

A

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

23
Q

Describe Beta-Oxidation

A

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)

24
Q

Where does Beta-Oxidation occur?

A

Mitochondrial Matrix

25
Q

What is made during each cycle of Beta-Oxidation?

A

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

26
Q

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

A

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

27
Q

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

A

These can enter the TCA cycle for further oxidation

28
Q

What are the four main chemical steps in beta-oxidation

A
  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)
29
Q

Describe beta-oxidation in unsaturated FAs

A

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

30
Q

Describe beta oxidation of long chain FAs

A

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

31
Q

Describe beta oxidation of odd chain FAs

A

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

32
Q

Describe the regulation of fat catabolism via supply

A

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

33
Q

Describe the intracellular regulation of fat catabolism

A

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

Biochemistry (7 decks)

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