Fatty Acid Oxidation Flashcards Preview

DEMS: Unit II > Fatty Acid Oxidation > Flashcards

Flashcards in Fatty Acid Oxidation Deck (9)
Loading flashcards...

Reason why fatty acids are preferred fuel source for liver, heart, and muscle at all times

  • More reduced than proteins or carbohydrates
    • More energy can be extracted when oxidized
    • Hydrophobic = not as hydrated as proteins or carbohydrates
      • Explains why fatty acids evolutionarily chosen over glycogen for most significant energy store in body
  • In fasting state, most energy for skeletal and cardiac muscle contraction comes from oxidation of fatty acids released from adipose tissue
  • Yield from complete oxidation of fatty acid --> CO2 and H2O = 9kcal/g of fat
    • Compared to 4kcal/g of protein or carbohydrate


Reasons why fatty acids are major energy source for all tissues in starvation conditions

  • Starvation conditions: fatty acids released from triacylglycerols by hormone-sensitive lipases
  • FFAs released into blood, transported to liver, muscle, etc. by association with albumin
  • Fatty acids then degraded by beta-oxidation
  • Fatty acids not delivered to brain because they cannot cross BBB


3 stages of fatty acid oxidation (beta-oxidation)

  1. Release of fatty acid from TAG
    • Initiated by hormone-sensitive lipase -- removes fatty acid from from carbon 1 and/or 3 of TAG
      • HSL activated by epinephrine
  2. Transport into mitochondrial matrix
    • Fatty acid group transferred temporarily to carnitine (catalyzed by CPT) because Acetyl CoA cannot enter mitochondrial matrix
    • Major regulatory step in fatty acid oxidation
    • Inhibited by malonyl CoA (intermediate of synthesis)
  3. Repeated cycles of oxidation
    • Beta-oxidation: major pathway
    • So named because b-carbon gets oxidized
    • Each cycle of oxidation has 4 steps --> yield 2 carbon acetyl CoA, 1 FADH2, 1 NADH


Beta oxidation pathway: 4 steps, critical intermediates, enzymes, cofactors

  1. Acyl CoA dehydrogenase
    • Located in mitochondrial matrix
    • Oxidizes acyl CoAs
    • 4 forms of enzymes: short (4-8), medium (8-14), long (12-18), and very long, carbon chains
    • Uses FAD and introduces trans double bond
    • Genetic defects in all 4 enzymes exist
      • Causes severe hypoglycemia provoked by fasting
      • MCAD (medium chain enzyme) deficiency is cause of some cases of SIDS
  2. Enoyl CoA hydratase
    • Adds water across trans double bond created in #1
  3. beta-hydroxy CoA dehydrogenase
    • Oxidizes hydroxyl generating b-keto-acyl-CoA and NADH from NAD
  4. Thiolase
    • Releases acetyl CoA, transfers fatty acid shortened by two carbons to CoA-SH for another round of oxidation
    • Malonyl CoA inhibits CPT and FA breakdown/beta oxidation


Fatty acid degradation vs. synthesis (summary) -- this is a table from the slides, you probably don't have to know all of it but maybe the general idea. 



3 ketone bodies

  1. Acetoacetate
  2. 3-hydroxybutarate
  3. Acetone
    • derived from spontaneous degradation of acetoacetate


Synthesis and use of ketone bodies

  • All water-soluble, transportable forms of acetyl units
  • When fatty acid oxidation occurs in liver, some acetyl units enter TCA cycle for eventual ATP generation; others used to produce ketone bodies
  • Production of ketone bodies by liver increases during fasting/very low carb diets


Result of overproduction of ketone bodies

Metabolic ketoacidosis


Surplus of ketone bodies in type 1 diabetes

  • Extremely high levels released during periods of extreme metabolic stress
  • Most commonly seen in type 1 diabetics when insulin levels drop too low (failure to take insulin, illness, stress, etc.)
  • Hormone-sensitive lipase highly activated --> releases fatty acids from adipose --> liver generates/releases high levels of ketone bodies
  • Ketone bodies (moderately strong acids) --> lower blood pH --> metabolic ketoacidosis
  • Sometimes can smell acetone on patient's breath