lipid metabolism during exercise. introduction 1.) energy density 2.) polar explorers/sled dogs...
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Lipid Metabolism During Exercise
Introduction1.) Energy Density
2.) Polar explorers/sled dogsAmerican Indians (pemican)
3.) Migrating fish and birds
4.) 3 sourcesplasma FFA from adipocytes (large > 50,000 kcals)intramuscular TG (2,000 -3,000 kcals)plasma TG (very small role during exercise in humans)
5.) Destabilizing effect on membranes High IMTG (obesity, type-II diabetes) linked with insulin resistance in muscle.
Storage and Mobilization of Triglycerides
Adipose Tissue Lipolysis
• Glycerol release, no Glycerol Kinase in adipocyte or muscle
, , Insulin, Lactate
re-esterification
FFA
Passive vs. Carrier-mediated
Fatty acid binding protein (FABP)EPI Insulin
B increases cAMP
Alpha decreases cAMP
Insulin activated PDE thus decreases cAMP
Hormone Sensitive Lipase• Phosphorylated by Protein Kinase A
– becomes active– catabolic in nature
Mechanism:Epinephrine binds to receptor on adipocytethis causes activation of AC – increase in cAMPcAMP activates Protein Kinase A
Insulin counteracts thisdeactivates Protein Kinase A via activation of PP-1, activates PDE which decreases cAMP
Regulation of Hormone-Sensitive Lipase
PKA
C
C
C OH
OH
OH
C C
O
C COH
Dehydration Synthesis
C
C
C C C
O
C CO
Triglyceride
C
C
C OH
OH
OH
+C C
O
COH
Glycerol FFA
H.S. Lipase
Hormone Sensitive Lipase
Adrenoceptor Blockade Schematic
FFA/Blood Glycerol at Rest and Exercise
Exercise 50%
Exercise 50%
Notice the magnitude of the change in FFA vs. glycerol
FFA Transport to Muscle Cells• Fatty Acids from adipose
– transported in blood via Albumin – 3 per– brought to muscle cell at fatty acid binding
receptor proteins– taken into muscle cell
Triglycerides in blood (chylomicrons and VLDL)broken down by lipoprotein lipase in capillary of the muscle before being taken into cell
FA transporters
1. FABPpm
2. FATP
3. FAT/CD36
Higher in ST vs. FT
Training has been shown to increase the amount of FA transporters in the PM.
Fatty Acid Transport Into Mitochondria
• FA can’t cross mitochondrial membrane
Must use carnitine acyl transferase (CAT) system
CAT Ilocated in outer wallBinds carnitine to FA, enabling it to pass inner mem.RATE LIMITING STEP IN FAT UTILIZATION!
CAT IIlocated in mitochondrial matrixremoves carnitine from FA
Fatty Acid Transport Into Mitochondria (cont.)Step 1:
FFA Fatty Acyl CoA(Acyl CoA synthase – in outer wall)
Fatty Acyl CoA Fatty Acyl CarnitineCAT I
Fatty Acyl Carnitine CAT II Fatty Acyl CoA (inside mitochondrial matrix)
Step 2:
Step 3:
*With training, number of mitochondria, CAT I , fat use with exercise.
-Oxidation Cycle
*No rate limiting steps in -Oxidation cycle! Rate limiting step occurs with CAT I.*
OHC C C C
O
FFA
ATP
AMP
CoAS H
H2O
Step 1:
Acyl CoA Synthase
~SC C C
O
CoA
HH
H H Fatty Acyl CoA
Step 2:
~SC C C
O
CoA
HH
H H
Fatty Acyl CoA
FAD
FADH2
Acyl CoA Dehydrogenase
~SC C C
O
CoA
H
H Enoyl CoA
(trans dehydrogenase rx)
**Recall: Fatty Acyl CoA is transported into mitochondria via CAT I & II complex**
~SC C C
O
CoA
H
Enoyl CoA
Step 3:
H2O (add to make 2° -OH)Enoyl CoA Hydrase
~SC C C
O
CoA
H
H
OH
L-Hydroxyacyl CoAH
H
~SC C C
O
CoA
H
H
OH
L-Hydroxyacyl CoAH
Step 4:
NAD
NADH + H
L-Hydroxyacyl Dehydrogenase
(oxidize 2°-OH to keto)
~SC C C
O
CoA
HO
Keto AcylH
()( Carbon)
Step 5:
~SC C C
O
CoA
HO
Keto AcylH()
CoASH
~SC
O
CoA
Acyl CoA~SC C
O
CoA
H
H Acetyl CoA (on to Krebs cycle)
H
Ketothiolase-oxidation? () carbon oxidized from saturated to keto NAD & FAD are reduced!
Energy yield of Palmitic Acid(16 C - FS - FA)
C C C C C C C C C C C C C C C C
7 FADH2 x 2 = 14
7 NADH2 x 3 = 21
8 Acetyl CoA x 12 = 96_
131__-2
129 ATP
Activation with Co ASH
ATP AMP
In CAC:3 NADH
1 FADH
1 ATP
GlycerolC
C
C OH
OH
OH
Glycerol
Glycerol kinase only in liver
ATP ADP C
C
C O~P
OH
OH
Glycerol 3-P
H
NAD
NADH2
(Glycerol P dehydrogenase)
C
C
C O~P
O
OH
DHAP
gluconeogenesis
glycolysis
Muscle Glycogen vs. FFA Expenditure
Substrates Providing Energy
Plasma Triacylglycerol
FABP
VLDL
Chylomicron
- 50%
- 85%LDL
1. 10% of fat use
2. Slow twitch Fast twitch3. LPL activity 1 hr of exercise
2 - 8 hr 2x LPL~~
Blood 80% H2O
FFA - Albumin TriC |C|C
Lipoprotein Lipase
FFA
In VLDL and chilomicrons
Triglyceride Breakdown for EnergyC
C
C O C
O
C C C
Triglyceride
HSL
C
C
C OH
OH
OH
HO C C C C
O
Glycerol FFA
+
Step 1:
Both muscular contraction and Insulin translocate FAT/CD36 from intracellular sites to plasma membrane. Recent studies have found the effects of insulin and muscular contraction to be additive, suggesting separate ICF pools of FA transporters.
Beta oxidation of FA in the mitochondria increases acetyl-CoA
and citrate concentrations.
AMPK prevents formation of malonyl Co-A, which is a allosteric inhibitor of CAT I, thus AMPK increases FFA uptake into mitochondrial matrix
Triglyceride FormationC
C
C OH
OH
OH
HO C C C C
O
GlycerolFFA
H2O(Dehydration Synthesis)
+
C
C
C O C
O
C C C
Triglyceride