Fatty Acid Oxidation

Cell Metabolism
Lipids

Fatty acids are cut into two carbon fragmetns to become acetyl-CoA

Fatty Acid Degradation/Oxidation:

• THINK MNEM Oxidation OHOT

FAO Regulation

Function/Purpose:

• Create energy like burning fats

Fundamentals:

Interlinkages

• Glycerol – DHAP+GAP – Glycoysis
• Glycerol – DHAP+GAP-Gluconeogenesis
• 8AcCoA – TCA
  • Acetyl CoA
  • Ketone Bodies
  • Sterols and FAs
• 7FADH+7NADH – ETC
  • Overall = 106 ATP fuel everything

Stages:

• 1Lipids must be mobilized – degradation of fatty acids and glycerol
• 2Fatty acids must be activated and transported into the mitochondria for degradation
• 3Hormone sensitive lipase initiates the process

''Phase 1 Summary CYTOSOL''
Reaction is catalyzed by a hormonally controlled lipase
Adipose tissue – horomonestrigger a 7tm receptor to activate adenylate cyclase
Glucagon and epinephrine - induce lipolysis (Regulat the use of triacylglycerol stores in muscle)
Increased levels of cAMP stimulates the protein kinase A
Perilipin A  - restructures the fat droplet so that the triacylglycerols are more accessible to the hormone sensitive lipase
        Hormone sensitive lipase – initiates hydrolysis
Produces:
Glycerol
Glycerol is absorbed by the liver and phosphorylated
Glycerol is taken up by the liver for pyruvate/Glycolysis and glucose/Gluconeogenesis
Glycerol – glycerol kinase – L-glycerol3phosphate
    L-glycerol-3-phosphate – glycerol phosphate dehydrogenase – DHAP (triose isomerase) GAP
Fatty Acids
Fatty acids are taken up by the serum albumin to other tissues for FA oxidation into acetyl CoA and CAC
Released fatty acids are not soluble in blood plasma

''Phase 2 Summary CYTOSOL/MITOCHONDRIA(Surface)''
STEPS
1    Formation of Acyl CoA
        FA + ATP<-> Acyl Adenylate
        Acyl Adenylate + AcCoA <-> Acyl CoA
Made irreversible by the hydrolysis of inorganic pyrophosphate
2    Carnitine Linkage
        Acyl CoA + Caritine (Caritine Acyltransferase I/Caritine Palmitoyl Transferase I) Acyl Caritine
        Caritine Acyltransferase is bound to the outer mito membrane
3    Shuttled Across IMM
        Translocase shuttles into IMM
        Acyl Caritine + CoA (Caritine Acyltransferase II) Caritine + Acyl CoA
''Phase 3 Summary MITOCHONDRIA''
Outer mitochondrial membrane where it is catalyzed by acyl CoA synthetase
Acetyl COA, NADH, FADH2 are generated by fatty acid oxidation
Oxidize the fatty acid – two carbons at a time
STEPS: (Even Fatty Acids)
1    Oxidation:
Acyl CoA - acyl CoA dehydrogenase – trans-delta2-enoyl CoA
FAD rather than NAD is the electron acceptor
dG for this reaction is insufficient to drive the reduction of NAD
2    Hydration:
trans-delta2-enoyl CoA - enoyl CoA hydratase – L-3hydroxyacyl CoA
Stereospecific – only the L isomer of 3-hydroxyacyl CoA is formed when hydrated\
oxidized the methylene group at the C3 to a keto group
3    Oxidation:
L-3hydroxyacyl CoA – L-3hydroxyacyl CoA dehydrogenase – 3-ketoacylCoA
        NAD rather than FAD
4    Thiolysis:
 3-ketoacylCoA - beta-ketothiolase - Acetyl CoA + Acyl CoA(-2C)
5    Repeat 1
Fatty Acid Catabolism Summary:

• Complete oxidation of palmitate yields 106 molecules of ATP
  • 8 acetyl CoA
  • FADH2
  • 7NADH
    • (2 molecules of ATP to activate palmitate)