Lipid metabolism Flashcards Preview

ESA 2 - MEH > Lipid metabolism > Flashcards

Flashcards in Lipid metabolism Deck (22)
Loading flashcards...
1
Q

Why do lipids produce more energy than carbohydrates?

A

Are more reduced (i.e. contain less O and more H per C atom) so release more energy when oxidised.

2
Q

Name the 3 classes of lipids.

A
  1. Fatty acid derivatives
  2. Hydroxy-methyl-glutaric acid derivatives (C6 compound)
  3. Vitamines
3
Q

Give examples (inc their role) of fatty acid derivatives.

A
  • Fatty acids (fuel molecules)
  • Triacylglycerols (fuel storage and insulation)
  • Phospholipids (membrane components and plasma lipoproteins)
  • Eicosanoids (local mediators)
4
Q

Give examples (inc their role) of hydroxy-methyl-glutaric acid derivatives.

A
  • Ketone bodies (C4) (water-soluble fuel molecules)
  • Cholesterol (C27) (membranes and steroid hormone synthesis)
  • Cholesterol esters (cholesterol storage)
  • Bile acids and salts (C24) (lipid digestion)
5
Q

Give examples of lipid-soluble vitamins.

A

Vitamins A, D, E and K

6
Q

What is the major dietary and storage lipid in the body? Where are they stored?

A
  • Triaglycerols

- Hydrophobic so stored in anhydrous form in a highly specialised storage tissue = adipose tissue

7
Q

Describe the structure of triaglycerols.

A

Consist of 3 fatty acids (usually long chain of about 18C) esterified to glycerol (can be broken down via lipolysis).

8
Q

What are triaglycerol fuel stores mainly used for?

A

Prolonged aerobic exercise, stress situations such as starvation and during pregnancy

9
Q

How are triaglycerol stores controlled?

A

Hormonal control

  • Storage promoted by insulin.
  • Storage reduced by glucagon, adrenaline, cortisol, growth hormone, thyroxine
10
Q

What happens to triglycerides in the GI tract after ingestion?

A

Hydrolysed by pancreatic lipase in the small intestine to release glycerol + fatty acids. Process also requries bile salts and colipase.

11
Q

What happens to the glycerol produced from triaglycerol hydrolysis in the GI tract?

A

Dissolves into bloodstream and is transported to liver where it is metabolised (e.g. reused for triaglycerol synthesis or used in glycolysis via DHAP intermediate)

12
Q

Why are some fatty acids essential dietary components, and others non-essential?

A
  • Saturated fatty acids (no C-C double bonds) = non-essential components as can be synthesised from carbohydrates and certain amino acids.
  • Unsaturated fatty acids (>1 C=C double bonds) = essential components as cannot be synthesised in body - mammals cannot introduce a double bond beyond C9.
    E.g. arachidonic acid = important polyunsaturated fatty acid as is starting point for synthesis of eicosanoid local mediators, inc prostaglandins.
13
Q

How are fatty acids produced by lipolysis in the GI tract transported to adipose tissues? And then from adipocytes to tissues to be used as energy?

A
  1. converted to lipoproteins - chylomicrons - in gut epithelial cells to allow diffusion in blood.
  2. bound non-covalently to albumin (= non-esterified FAs or free FAs).
14
Q

Which tissues can or can’t use fatty acids as an energy source?

A
  • Many tissues inc. liver, heart muscle and skeletal muscle can.
  • RBCs can’t as don’t possess mitochondria to perform FA beta-oxidation.
  • WBSc can’t as mitochondria are involved in oxidative burst for ROS generation.
  • CNS cells (brain and spinal cord) can’t as FAs do not readily cross the blood-brain barrier.
15
Q

Why does low extracellular [glucose] result in fatty acid release as an alternative fuel?

A
  • Fat store in adipose tissue is dynamic - triglyceride/FA cycle: triglycerides continuously broken down (lysis) to FAs and recombined with glycerol-1-P (esterification) to reform triglyceride.
  • Released glycerol moves to liver so need a constant supply of glucose to regenerate glycerol-1-P store.
  • So low extracellular [glucose] in starvation reduces [glycerol-1-P] and ability to synthesise triglycerides.
  • So FA released into circulation (bound to albumin).
16
Q

What are the 3 steps in FA catabolism?

A
  1. FA is activated by linking to CoA
  2. Transported across inner MT membrane using a carnitine shuttle
  3. FA beta-oxidation: cycles through sequence of oxidative reactions, with 2C removed at each cycle
17
Q

How are FAs “activated”?

A

Fatty acyl CoA synthase links FA to coenzyme A (via high energy bond - requires ATP). Forms fatty acyl~CoA.

18
Q

How are activated fatty acyl~CoA transported across the inner MT membrane?

A

Carnitine shuttle transport:

  1. Carnitine bound to acyl~CoA (by CAT1 carnitine acyltransferase), releasing CoA and producing acyl carnitine.
  2. Acyl carnitine transported across inner membrane into matrix by carnitine shuttle transporter.
  3. CoA bound to acyl carnitine (by CAT2 carnitine acyltransferase), releasing carnitine and producing acyl~CoA.
  4. Carnitine returned to intermembrane space by transporter.
19
Q

How does the FA transport system into MT regulate the rate of fatty acid oxidation?

A
  • Transport of activated FAs into MT is inhibited by malonyl CoA (= FA synthesis intermediate).
  • Important as prevents FAs newly synthesised in cytoplasm from being immediately transported into MT and oxidised.
20
Q

What are the consequences of defective MT FA transport systems in patients?

A
  1. Poor exercise tolerance

2. Unusually large amounts of triaglycerols in muscle cells

21
Q

What does the beta-oxidation of FAs involve? What molecules are required and produced?

A
  • Cycle of reactions (TCA cycle + oxidation) that oxidises the FAs and removes a 2C unit (acetate) until only 2C atoms remain.
  • Requires: CoA, ATP, FAD+, NAD+, H2O and O2 (for stage 4 to reoxidise the NADH and FADH2 formed).
  • Produces: acetyl~CoA (from FAs), AMP + Pi, FADH2 and NADH (from oxidising agents) and H+.
    I.e. No direct ATP synthesis
22
Q

Why is acetyl-CoA such an important molecule in metabolism?

A
  1. Main convergence point for catabolic pathways
    - produced using pyruvate, fatty acids, amino acids and alcohol
    - CH3CO group linked to CoA via S-atom: high energy of hydrolysis
  2. Also an important intermediate in anabolic pathways. Starting point for biosynthesis of:
    - fatty acids and then glycerol or phospholipids
    - hydroxymethyl glutaric acid (3 acetyl-CoA condensed) and then ketone bodies or cholesterol (and then steroid hormones)