Lipolysis

1
Lipolysis
2
Lipolysis

• Largest storage form of energy
• Provides energy at the slowest rate
• Stored
• adipose tissue
• muscle
• Brain, CNS, abdomen, etc.
• Use of lipids spares glycogen during prolonged
  work

3
Lipids

• Substance that is water insoluble, but soluble in
  organic solvents
• Most are Non-polar (uncharged)
• Important in a variety of roles

4

• Cholesterol
• Sterol Comes from diet or is synthesized in
  liver
• Important Cell membrane structure
• Steroid hormone synthesis
• Testosterone, Estrogen, Corticosteroids

5

• Derived from incomplete Fat metabolism
• Formed from excess Acetyl-CoA
• Krebs cycle slows due to low CHO stores
• 2 Acetyl-CoA molecules
• Acetoacetyl-CoA
• Acetoacetate
• D-ß-Hydroxybutyrate
• Last two used for energy

6

• Exception to polarity rule
• Found in cellular membranes
• Profers some selectivity to the membrane

7
Fat digestion

• Triglycerides
• Biggest percentage
• Cholesterol and phospholipids
• Digested in small intestine
• Bile emulsifying agent

8

• Pancreatic lipase
• Breaks down fat globule (Micelles)
• Monoglycerides, FFA and glycerol
• Taken up by small intestinal cells
• Repackaged with intestinal cells as Chylomicrons
• Released into lymph
• Different from carbs, most go to heart first

9
Chylomicrons and lipoproteins

• Two mechanisms of fat clearance from blood
• Transport to liver
• Uses fats for fuel
• Converts to lipoproteins
• Mix of trigs, phospholipids, cholesterol and
  protein
• Protein allows transport in blood

10
Lipoproteins

• Classified by density
• VLDL mostly triglycerides
• LDL mostly cholesterol
• HDL mostly protein

11
Uptake of fatty acids Lipoprotein lipase

• In capillary/cell interface of most tissues
• This enzyme facilitates uptake of FFA from blood
  after a meal
• Hormone sensitive lipase
• Essentially same enzyme
• Breaks down intracellular lipids in fasted state

12
Lipid utilization during exercise

• Primarily used
• Rest, prolonged low-moderate intensity exercise,
  recovery from exercise
• Complicated
• Multi-step
• Mobilization
• Circulation
• Uptake
• Activation
• Fatty-acyl-CoA
• Translocation
• ?-oxidation
• Mitochondrial oxidation

13
Mobilization

• HSL
• Breaks down stored triglycerides
• Stimulated by catecholamines (rapid phase)
• Growth hormone (prolonged phase)
• Triglycerides carried in blood by albumin

14
Circulation and uptake

• FFA circulated in blood bound to albumin
• Uptake
• Directly related to circulating concentration
• Rate of blood flow
• Increased flow, increased delivery, increased
  uptake and utilization

15
Activation and translocation

• FFA are taken up by FABP
• FAT (fatty acid transporter)
• Brings the FFA into the cell
• 3) Attachment of FA to CoA molecule
• Fatty acyl-CoA
• Outer mitochondrial membrane
• 4) Translocation
• Into mitochondrial matrix
• Carnitine and CAT1 and CAT2

1
2
3
4
16
ß-oxidation

• Breaks down FA-CoA to acetyl-CoA (2C fragment)
• Starts the process of fatty acid oxidation
• 16C FA requires
• 7 cycles of ß-oxidation
• Each cycle produces 1 Acetyl-CoA, 1 NADH and 1
  FADH2
• So 16C FA produces how many ATP?
• 8 acetyl-CoA, 7 NADH, 7 FADH2
• WHY 8 Acetyl-CoA?
• Each acetyl-CoA 12 ATP (3 NADH, 1 FADH, 1 ATP)
• Activation costs 2 ATP (equivalent, one ATP to
  AMP)

17
Oxidation of fatty acids

• After ß-oxidation
• Acetyl-CoA
• Enters Krebs cycle
• NADH and FADH go to electron transport chain

18
Free fatty acids rest and exercise

• Opposite of CHOs
• Fasted state raises FFA
• Most pronounced during low-to-moderate intensity
  exercise

19
Intramuscular triglycerides

• Stored in muscle much like glycogen
• Hormone Sensitive Lipase
• Breaks down trigs within cell
• Hard to quantify utilization
• Concomitant use by cell and uptake from blood

20
Intramuscular lipolysis

• Perhaps used in type I fibers
• Results suggest that they are used primarily
  during recovery from exercise

21
Lipid oxidation in muscle

• FFA are taken up by the muscle
• Training increases this ability
• Intramuscular TG
• Probably used when glycogen becomes depleted
• Most likely used in recovery
• Used to a great extent by diving mammals

22
Tissue specific fat metabolism

• Heart and liver specially adapted to fat
  utilization
• Brain, RBCs use glucose almost exclusively
• Muscle in between
• Type IIb use relatively little fat
• Type I use much more fat
• Muscle mitochondrial adaptations
• Much greater than those associated with the
  cardio-circulatory system (i.e. heart, capillary
  vol., etc.)
• Increases ability to use fat (particularly when
  glycogen is low)
• Note how FFA are utilized much more quickly when
  enzyme content is doubled

23
Crossover concept

• Biggest factor in Fuel selection
• Power output
• Rest
• Mostly fat used
• Exercise
• Depends on intensity
• Training
• Can shift fat curve to left
• Sympathetic nervous system stimulation
• Shifts fat curve right

24
Crossover concept

• Note that it is 50 fat-50 CHO at very low power
  output (30 Vo2 max)
• As power output rises, fat oxidation slows due
  to
• The complexity of the FA oxidation process
• Reduced blood flow to inactive tissues
• Sympathetic nervous system stimulation (which
  increases CHO utilization)
• Endurance training only affects the percentages
  slightly

25

• Glycerol
• Marker of FFA mobilization from fat stores
• This data suggest slightly greater mobilization
  after training at 45
• FFA
• Simultaneously mobilized into blood and taken up
  by the tissues
• Why are blood levels of FFA lower after training?

26

• Glycerol
• Rate of appearance
• Measure of mobilization
• Note that mobilization is greater following
  training
• FFA
• Appearance and disappearance
• Measure of turnover
• Note that prior to training
• FFA turnover falls with intensity
• After training
• Pattern is different

27
Ketosis Fuel source?

• Under starvation conditions
• When carbohydrate use is minimal
• Reduces protein catabolism for energy needs
• Ketone bodies
• Acetoacetate,
• ß-hydroxybutyrate
• Acetone

28

• Can be taken up by brain
• Converted to acetoacetate
• Converted to acetyl-CoA and oxidized
• Problems?