Fat metabolism - Lecture 156

 Fat Metabolism - Lecture 156

1. Understand how fatty acids are synthesised 

• Fatty acids are a major source of energy
• Synthesised from acetylCoA when energy is abundant
• Stored as triacylglycerols (TAG) - 3 long chain fatty acids 
• esterified to glycerol
• TAGs:
• non-polar
• non-toxic
• stored in large quantities in adipose tissue
• seen as large liquid droplets in cytosol
• Synthesis occurs by repeated condensation of 2 carbon units to build up an even numbered long chain fatty acid
• Cannot occur by reversing β-Oxidation

Fatty Acid Synthesis:

•  AcetylCoA carboxylase is limiting enzyme in step 1. 

• Pathway proceeds in cycles in which fatty acid chain grows by 2 Carbons in each turn
• All enzymes contained in one multi-enzyme complex - Fatty Acid Synthase
• When chain is 16C long, it is too big for enzyme and it is released. 

2. Identify key differences between the fatty acid breakdown and synthesis pathways

                             Synthesis                            Breakdown

site                        cytosol                                mitochondria
reducing agent      used (NADPH)                    produced (NADH/FADH2)
ATP                      used                                    produced
activation              acyl-carrier protein (ACP)    co-enzyme A

3. Show how fatty acids are released from body stores and broken down to obtain energy

3 steps involved: 

1. Lipolysis
2. Activation of fatty acid
3. β-Oxidation

Step 1 - Lipolysis: 

• Occurs in adipose tissue

Step 2 - Activation of Fatty Acids:

• must be activated by addition of CoA
• need ATP for high energy bonds
• forms fatty-acyl-CoA + AMP + 2Pi

Step 3 - β-Oxidation:

• occurs in matrix of mitochondria
• fatty acid enters inter-membrane space
• cannot cross, so acyl group is transferred to carrier molecule (carnitine) and acylcarnitine is transported across by carnitine translocase
• Carnitine transporter is inhibited by malonylCoA
• regulator to prevent synthesis and breakdown from occurring at the same time
• Inside matrix, acyl group transferred back to CoA
• Overall reaction
• fatty acids broken down completely to acetylCoA
• Palmatate (C16 chain) undergoes 7 cycles to produce 8 acetylCoA molecules
• ATP Produced = 106 net production
• 108 produced but uses 2 in FA activation step

Step 1: Dehydrogenation by FAD changes Carbon bonds

Step 2: Hydration changes Carbon bonds

Step 3: Oxidation converts hydroxl group to keto group

Step 4: Thiolysis - cleavage of β-ketoacylCoA

Repeat

4. Explain how ketone bodies are produced in the liver and used in the tissues.

Ketogenesis - Ketone bodies produced:

• When fat breakdown is main source of energy, acetylCoA accumulates
• It is converted to ketone bodies
• There are 3 ketone bodies:
• acetoacetate
• β-hydroxybutyrate
• acetone
• Acetone is a waste product
• β-hydroxybutyrate and acetoacetate are used in energy metabolism
• Produced in Liver and transported via blood to other tissues for energy generation

Ketone breakdown - ketone bodies used: 

• Occurs in Tissues
• β-hydroxybutyrate and acetoacetate are converted into acetylCoA
• This goes into CAC
• ketone bodies are normal fuels of respiration
• important sources of energy
• some tissues (e.g. the heart) prefer acetoacetate to glucose
• Brain adapts well to switch from glucose to acetoacetate during starvation and with diabetes mellitus, where ketone production increases