oxidation

1
? - oxidation
2
Fatty acid storage

• Dietary fatty acids form triacylglycerols in
  intestinal cells
• Released into lymphatic system as chylomicrons
• Lipoprotein lipase
• present in capillaries supplying adipocytes (and
  skeletal muscle)
• Hydrolyse fatty acids from triacylglycerols in
  chylomicrons/lipoproteins
• Fatty acids flow down concentration gradient via
  facilitated transport
• Stored as triacylglycerols

From Matthews, CK van Holde KE (1990)
Biochemistry. Redwood CityBenjamin Cummings
p.301.
3
Fatty acid release

• Triacylglycerols hydrolysed in adipocytes (and
  skeletal muscle) by hormone sensitive lipase
• Stimulated by sympathetic hormones and
  neurotransmitters
• Inhibited by insulin

From Matthews, CK van Holde KE (1990)
Biochemistry. Redwood CityBenjamin Cummings
p.301.
4
Fatty acid release

• Glycerol released by adipocytes and skeletal
  muscle
• Adipocytes and SM do not contain glycerol kinase
• Glycerol converted to glycerol 3-phosphate in
  cells containing glycerol kinase (i.e. liver)
• G-3-P converted to DHAP
• Glycolysis
• Gluconeogenesis
• New data suggest that SM may metabolise some
  glycerol despite not containing glycerol kinase
• Fatty acids
• In adipocytes
• Some reesterified to triacylglycerols
• Some released and attach to albumin to form FFA
• In skeletal muscle
• Used as fuel

5
Fatty acid oxidation

• Fatty acids oxidised in mitochondria
• Must be activated before entering mitochondrial
  matrix
• Combine with CoA on outer membrane to form Acyl
  CoA
• Energy provided by hydrolysis of ATP

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 559.
6
Fatty acid oxidation

• Acyl CoA transported across inner mitochondrial
  membrane by carnitine transporter
• Rate limiting step for fatty acid break down

From Stryer, LS (1988) Biochemistry (3rd Ed).
New York WH Freeman Co. p471
7
Fatty acid oxidation

• Once inside mitochondria Acyl CoA oxidised via
  ?-oxidation
• Two carbons at a time removed from hydrocarbon
  tail to form acetyl CoA
• Split between ? and ? carbons

From Stryer, LS (1988) Biochemistry (3rd Ed).
New York WH Freeman Co. p470
8
Fatty acid oxidation

• Acyl CoA dehydrogenated to form enoyl CoA
• Produces
• double bond between ? and ? carbons
• FADH

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 559.
9
Fatty acid oxidation

• Enoyl CoA hydrated to form hydroxyacyl CoA
• Saturates double bond between ? and ? carbons
• Changes energy distribution within molecule

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 559.
10
Fatty acid oxidation

• Hydroxyacyl CoA oxidised to form ketoacyl CoA
• H removed from hydroxyl group on ? carbon
• Produces NADH H

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 559.
11
Fatty acid oxidation

• ketoacyl CoA split between ? and ? carbons and
  another CoA added
• Produces
• Acetyl CoA
• Acyl CoA which has been shortened by 2 carbons

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 559.
12
Fatty acid oxidation

• Acyl CoA which has been shortened by 2 carbons
• Process continues until final product is two
  acetyl CoA
• Acetyl CoA and propionyl CoA (3C) final products
  of odd chain fatty acids
• Propionly CoA converted to succinyl CoA and
  enters KC

From Summerlin LR (1981) Chemistry for the Life
Sciences. New York Random House p 559.
13
Ketone bodies

• When body CHO stores low blood glucose also low
• decreased insulin production
• Insulin inhibitor of lipolysis
• Low insulin leads to accelerated lipolysis
• High blood FFA leads to increased extraction by
  liver
• acetyl CoA production via ?-oxidation increased
• Liver cells use oxaloacetate to synthesise
  glucose to combat falling blood glucose levels
• Leaves less to combine with acetyl CoA for entry
  into KC
• Liver contains enzymes that make ketone bodies
  from acetyl CoA
• Acetoacetate
• reduced to form D-3-hydroxybutyrate
• Spontaneous decarboxylation forms acetone
• Ketone bodies used as fuel by other tissues
• ketoacidosis - reduced pH can be fatal in
  uncontrolled diabetes mellitus