Department of Biochemistry and Molecular Biology

1
When is there need to oxidize fatty acids?

• During periods of extended exercise e.g aerobics,
  running on a treadmill, running for distances
  longer than 100 yards.
• In diabetic patients in whom glucose metabolism
  is low.
• During periods of starvation.
• By heart muscle which almost exclusively depends
  on FA oxidation for energy.

2
Fatty Acid Oxidation

• Mobilization of Fat
• Transport of fatty acids and their activation in
  the cells
• Transport to mitochondria and oxidation
• Formation of ketone bodies (excess oxidation in
  starvation and diabetes)
• Regulation of fatty acid oxidation

3
Mobilization of Fat

• Fat cell

Glucagon
Glucagon receptor
Adenylate cyclase
cAMP ATP
Activates
Protein Kinase A
ADP ATP
HSL Phospho-HSL
TG Glycerol FA
Blood
4
Transport of Fatty Acids

• Primarily bound to albumin
• Small fraction bound to globulin fractions

Cytosol
FA-FABP
Fatty acids
Albumin
P-P AMP ATP CoA
Fattyacyl CoA synthetase
Fattyacyl-SCoA
Mitochondria
Muscle cell
5
Transport of Fattyacyl-CoAs to Mitochondria

Fattyacyl-CoA
Outer Membrane
Cytosol
Oxidation of fattyacyl -CoA
Matrix
Mitochondria
Inner Membrane
6
Formation of Fatty acyl Carnitine

• Fattyacyl Carnitine Formation

7
Transport to Mitochondrial Matrix
8
Mitochondrial oxidation of FA
9
Overall Scheme of oxidation

• One Step of FA Oxidation

10
Oxidation of Odd Chain Fatty Acids

• Odd chain FA undergo normal ß-oxidation

11
Some abnormalities of FA oxidation seen in the
clinic

• Carnitine deficiency Fatigue, lipid accumulation
  in muscles
• MCAD-medium chain fattyacyl CoA dehydrogenase
  mutations Autosomal recessive inherited
  disorder abnormal enzyme with limited enzyme
  activity. Homozygous individuals show extreme
  fatigue, perspiration, vomiting, coma and
  sometimes death. Some evidence of MCAD mutations
  in SIDS.

12
Oxidation of Odd Chain Fatty Acids

• Odd chain FA undergo normal ß-oxidation

13
Regulation of FAO

• 1. Enzyme CPTI (carnitine-palmitoyl transferase
  I) is the rate limiting enzyme. It is inhibited
  by Malonyl CoA, a product formed during fatty
  acid synthesis)
• 2. Hormonal Regulation
• Glucagon
• Epinephrine
• Insulin

Hormone sensitive lipase
14
Learning Objectives

• What is the mechanism of the release of fatty
  acids from adipose tissue?
• How are fatty acids transported in plasma?
• Which chemical form of fatty acid is oxidized in
  mitochondria and how does it get there?
• What is the role of carnitine in fatty acid
  oxidation?
• What are the consequences of deficiencies of
  factors and enzymes of fatty acid oxidation?
• How can abnormalities of fatty acid oxidation be
  compensated for using different dietary regimens?
• Why and how are ketone bodies produced and
  utilized?