• solubilized in intestinal tract by bile salt → create miscelles
• Cleaved to free fatty acids (FFA) and monoacylglycerol by pancreatic lipases.
  

• Transported to tissues via the lymphatic system and then to the circulation.

• Mainly constitued of triglycerides
  
• Chlymicrons become progressively heavier, as triglycerides are delivered to the tissues
• VLDL: Very low density lipoportein
  
• LDL: low density lipoprotein
  
• HDL: high density lipoprotein
  

• must be hydrolyzed in order to be biochemically accessible to tissues like muscle
  
• Must be degraded to fatty acids and glycerol
  
• released from adipose-tissue to energy-requiring tissues
  

Hormone binds to 7TM receptor embedded within the membrane, stimulating it → GDP diffuses out and GTP diffuses in→ βγ dimer dissociates βγ → α dimer binds to adenyl cyclase, activating it → uses ATP in order to turn on cAMP → activates Protein Kinase A → Activates Triacylglycerol lipase → Breaks down triacylglycerol to diacylglycerol→which is then converted to free fatty acids by other lipases and the release of glycerol

Oxidation of Fatty Acids:

Where does it take place?

What must occur before fatty acids can be oxidized?

• Occurs in mitochondrial matrix
• Fatty acids must be activated by attachment to coenzyme A (CoA)
  
• Activated fatty acids need to be transported into the matrix
  

• Fatty acids are attached to CoA
• Enzyme: Acyl CoA synthetase (Fatty acid thiokinase)
• Two step rxn → catalyzed by same enzyme
  
• Proceeds through acyl-adenlyate (acyl-AMP) intermediate
• energy to derive the reaction come from the conversion of ATP → ADP + PPi
  

• Activated fatty acids cross inner mitochondrial membrane esterified to carnitine
  
• Enzyme: carnitine acyl transferase I
  
• Energy of O-acyl bond comparable to thioester
  

• Acylcarnitine enters mitochondria through action of translocase
  
• Two different acyltransferase enzymes → one on each side of membrane
  

β Oxidation of Fatty Acids:

Where it takes place?

Substrates?

Products?

• Occurs in mitochondria
• Substrates → Fatty Acids and ATP
• Products → Acetyl CoA, NADH, and FADH₂
  

• Begins with Aceyl CoA
• Oxidation (FAD → FADH₂)
• Hydration
• Oxidation (NAD+ → NADH)
• Tholysis

• oxidizes FA chain between carbons 2 and 3 (the β and γ carbons)
• Creates double bond
  
• Electrons used to reduce FAD to FADHS → enters electron transport chaing through Electron Transfer Flavoprotein (ETF) at complex II
  

• Adds water across double bond
  
• Stereo specific → forms chiral product

• electrons transferred to NAD+
• Makes a ketoacyl FA
  

• Ketothiolase: "breaks" bond between carbons 2 and 3
  
• Thiol group in active site attacks keto carbon → releases acetyl CoA and makes a thioester bond between fatty acyl chain and enzyme
• AcetylCoA displaces the enzyme thiol group to restore an activated FA
  

Oxidation of Palmitate:

How many rounds of β oxidation required for complete oxidation of palmitate to acetyl CoA?

How many molecules of acetyl CoA produced?

How much ATP produced?

• 7 rounds of oxidation
  
• 8 molecules of acetyl CoA produced
  
• 106 ATP produced
  

Oxidation of Unsaturated Fatty Acids:

configuration

Energy difference between FA w/ double bonds and saturated fatty acids

• cis double bonds must be converted to trans configuration for oxidation to carry on
  
• oxidation of FA w/ double bonds yields less ATP energy than saturated acids
  

Oxidation of Monounsaturated FA:

What are the obstacles faced?

What is the solution?

• Obstacle: original 9, 10 doule bond → after 3 rounds of oxidation → 3,4 cis instead of 2, 3 trans double bond → not a substrate for the hydratase
• Solution: converts Δ3 cis bond to Δ2 trans bond
  

Oxidation of Polyunsaturated FA:

What are the obstacles?

What is the solution?

• original 9,10 double bond → after 3 rounds of oxidation → have a 3,4 cis instead of 2,3 trans double bond
  
• polyunsatured FA: original 12, 13 double bond → after starting 5th round of oxidation → a conjugated cis 4,5 trans 2,3 molecule
• Solution: need 2 enzymes
• Isomerase → converst cis Δ3 to bond to trans Δ2
• Reductase→ converts cis Δ4 bond to trans Δ3 bond
  

• fuel source under glucose deprived conditions
• Pass the blood brain barrier
• oxidized back to acetyl CoA in tissues
• Synthesis in mitochondria
• Degradation in cytosol
  

• Synthesized from acetyl CoA → 2 acetyl CoA molecules condensed, breaking a thioester bond in the process (releasing energy)
• Acetyl CoA condense w/ a 3rd acetyl CoA and water to make HMGCoA
• HMGCoA is cleaved to make acetoacetate and acetyl CoA