Lipolysis

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

Lipids• Substance that

is water insoluble, but soluble in organic solvents

• Most are Non-polar (uncharged)

• Important in a variety of roles

Cholesterol:•Sterol: Comes from diet or is synthesized in liver•Important: Cell membrane structure•Steroid hormone synthesis

•Testosterone, Estrogen, Corticosteroids

•Derived from incomplete Fat metabolism•Formed from excess Acetyl-CoA•Kreb’s cycle slows due to low CHO stores•2 Acetyl-CoA molecules

•Acetoacetyl-CoA•Acetoacetate•D-β-Hydroxybutyrate

•Last two used for energy

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

• Triglycerides– Biggest

percentage– Cholesterol

and phospholipids

– Digested in small intestine

– Bile: emulsifying agent

Fat digestion

• 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

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

Lipoproteins

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

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

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• Β-oxidation• Mitochondrial oxidation

Mobilization

• HSL– Breaks down

stored triglycerides– Stimulated by

catecholamines (rapid phase)

– Growth hormone (prolonged phase)

– Triglycerides carried in blood by albumin

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

Activation and translocation1) FFA are taken up by

FABP2) 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

β-oxidation• Breaks down FA-CoA to acetyl-CoA (2C fragment)• Starts the process of fatty acid oxidation• 16C FA requires:

– 7 cycles of β-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)

Oxidation of fatty acids

• After β-oxidation– Acetyl-CoA

• Enters Kreb’s cycle

– NADH and FADH go to electron transport chain

Free fatty acids: rest and exercise

• Opposite of CHOs– Fasted state

raises FFA– Most

pronounced during low-to-moderate intensity exercise

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

Intramuscular lipolysis• Perhaps used in type I fibers

• Results suggest that they are used primarily during recovery from exercise

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

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

• 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

Crossover concept

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

• 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?

• 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

Ketosis: Fuel source?• Under starvation

conditions– When carbohydrate

use is minimal– Reduces protein

catabolism for energy needs

– Ketone bodies• Acetoacetate, • β-hydroxybutyrate • Acetone

• Can be taken up by brain

• Converted to acetoacetate

• Converted to acetyl-CoA and oxidized

• Problems?