Transcript Lipid Metabolism During Exercise

Lipid Metabolism During
Exercise
Introduction
1.) Energy Density
2.) Polar explorers/sled dogs
American Indians (pemican)
3.) Migrating fish and birds
4.) 3 sources
plasma 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 adipocyte
this causes activation of AC – increase in cAMP
cAMP activates Protein Kinase A
Insulin counteracts this
deactivates Protein Kinase A via activation of PP-1,
activates PDE which decreases cAMP
Regulation of HormoneSensitive Lipase
PKA
C
C
C
OH
OH
OH
O
HO
C
C
C
C
Dehydration Synthesis
C
O
C
C O C C
C
C
H.S.
Lipase
Triglyceride
C
C
C
OH
OH
OH
Glycerol
O
+
HO
C
C
FFA
C
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 I
located in outer wall
Binds carnitine to FA, enabling it to pass inner mem.
RATE LIMITING STEP IN FAT UTILIZATION!
CAT II
located in mitochondrial matrix
removes carnitine from FA
Step 1:
Fatty Acid Transport Into
Mitochondria (cont.)
(Acyl CoA synthase – in outer wall)
FFA
Fatty Acyl CoA
Step 2:
Fatty Acyl CoA
CAT I
Fatty Acyl Carnitine
Step 3:
Fatty Acyl Carnitine
CAT II
Fatty Acyl CoA (inside
mitochondrial matrix)
*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.*
Step 1:
O
C
C
C
C
OH
FFA
Acyl CoA
Synthase
ATP
CoAS H
AMP
H2 O
H
H O
C
C
H H
C ~S CoA
Fatty Acyl CoA
Step 2:
H
H O
C
C
C ~S CoA
H H
**Recall: Fatty Acyl
CoA is transported into
mitochondria via CAT I
& II complex**
Fatty Acyl CoA
FAD
Acyl CoA
Dehydrogenase
(trans dehydrogenase rx)
FADH2
H O
C
H
C
C ~S CoA
Enoyl CoA
Step 3:
H O
C
C
C ~S CoA
H
Enoyl CoA
H2O (add to make 2° -OH)
Enoyl CoA Hydrase
OH H O
C
C
H H
C ~S CoA
L-Hydroxyacyl CoA
Step 4:
OH H O
C
C
C ~S CoA
H H
L-Hydroxyacyl CoA
NAD
L-Hydroxyacyl
Dehydrogenase
(oxidize 2°-OH to keto)
NADH +
H
( Carbon)
O
H O
C
C
C ~S CoA
()
H
Keto Acyl
Step 5:
O
H O
C
C
C ~S CoA
()
H
Ketothiolase
O
C ~S CoA
Acyl CoA
Keto Acyl
-oxidation?
CoASH () carbon oxidized
from saturated to
keto  NAD & FAD
are reduced!
H O
H C
H
C ~S CoA
Acetyl CoA
(on to Krebs cycle)
Energy yield of Palmitic Acid
(16 C - FS - FA)
C C C C C CC C C C C C C C C C
7 FADH2 x 2 =
14
7 NADH2 x 3 =
21
8 Acetyl CoA x 12 =
In CAC:
3 NADH
1 FADH
1 ATP
Activation with Co ASH
96_
131
__-2
129 ATP
ATP  AMP
Glycerol
C
C
OH
OH
C
OH
Glycerol
ATP
ADP
Glycerol
kinase
only in
liver
C
H C
C
OH
OH
O~P
Glycerol
3-P
(Glycerol P
NAD
dehydrogenase)
NADH2
C
C
C
DHAP
OH
O
O~P
gluconeogenesis
glycolysis
Muscle Glycogen vs. FFA
Expenditure
Substrates Providing Energy
Plasma Triacylglycerol
VLDL - 50%
LDL
FABP
1.
2.
10% of fat use
Slow twitch
Fast twitch
3. LPL activity ~
~ 1 hr of exercise
2 - 8 hr
2x LPL
Chylomicron - 85%
FFA - Albumin
Blood 80% H2O
FFA
Tri
C
|
C
|
C
In VLDL and
chilomicrons
Lipoprotein
Lipase
Triglyceride Breakdown for Energy
Step 1:
C
C
O
C
O C
C
C
C
Triglyceride
HSL
C
C
OH
OH
C
OH
Glycerol
O
+
HO C
C
FFA
C
C
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 Formation
C
OH
C
C
OH
OH
Glycerol
+
O
HO C
C
C
C
FFA
H2O
(Dehydration Synthesis)
C
C
O
C
O C
C
C
Triglyceride
C