Title: Friday : Quiz and review session (no paper discussion). Extended review session if needed
1- Friday Quiz and review session (no paper
discussion). Extended review session if needed - Other review sessions? Thursday? Weekend?
- Extended office hours
- Exam. Multiple choice, matching, structures,
short answer, pathways, Diabetes
2Beta Oxidation Regulation Summary
- 1. Substrate availability-Plasma fatty acids
lipolysis (HSL) - Entry into mitochondria CPT I/malonyl CoA
- Redox state (FAD/FADHAcetylCoA/CoASH)
- 4. PPAR transcriptional regulation of those
genes involved in beta oxidation - Know the steps involved in beta oxidation
3Fed State
CPT1
FFA
FA-CoA
FA-CoA
(-)
box
(-)
Malonyl CoA
()
ACC
Acetyl CoA
Acetyl CoA
citrate
citrate
TCA
Pyruvate
Acetyl CoA
GLC
cytosol
mitochondria
blood
4FASTED STATE
CPT1
FFA
FA-CoA
FA-CoA
(-)
box
(-)
Malonyl CoA
()
ACC
Acetyl CoA
Acetyl CoA
citrate
citrate
TCA
liver
Ketone bodies
blood
cytosol
mitochondria
5Skeletal Muscle
- Main site of FA oxidation at rest and during
exercise
the maximum amount of oxygen that can be removed
from circulating blood and used by the working
tissues during a specified period.
Jeukendrup (2002) Ann. NY Acad. Sci. 967217-235
6Substrate shift
- Increase fatty acid oxidation
- Decrease carbohydrate oxidation
- Decrease glycolysis
- How does this occur?
7Energy expenditure increases with exercise
intensity
Muscle glycogen
Triglycerides
Plasma FFA
Plasma glucose
8Moderate Exercise
Increased lipolysis (epi activates
HSL) Increased FA release Increased blood
flow Increased FA oxidation in muscle Increased
accumulation of acetyl CoA
9The Randle Cycle
Glc
FFA
hexokinase
(-)
Citrate accumulation?
Glc-6P
Glc-1-P
(-)
PFK
FA-CoA
F 1,6 Bi-P
CPTI
Pyruvate
FA-CoA
(-)
PDH
b-ox
Acetyl CoA
Acetyl CoA
citrate
oaa
mitochondria
10Fed state
Fasted or Exercise
Glucose availability
Increased b oxidation
cytosolic citrate
(-)
()
(-)
(-)
(-)
Malonyl CoA
b Ox
PFK
ACC
Glycolysis
11Muscle contraction and ACC
Muscle contraction
AMP
Increase AMPK kinase activity
Increase AMPK activity
AMPKinase (active)
Decrease ACC activity
AMPkinase kinase
Decrease malonyl CoA
AMPkinase (inactive)
Increase CPT-I activity
Increase FFA oxidation
After Rasmussen and Wolfe. Annu. Rev. Nutr.
19463-484, 1999
12Long- and Medium-Chain Fatty Acid Oxidation is
Increased in Exercise-Trained Human Skeletal
Muscle Jong-Yeon et al. Metabolism 51(4) 2002
pp 460-464
13Hypothesis
- Skeletal muscle fatty acid oxidation is enhanced
by increasing entry into the mitochondria with
exercise training - Why study this?
- Why did they use both MCFA and LCFA?
14Methods
Percutaneous needle biopsy
Vastus lateralis
15C14
a
b
g
palmitate
FAD
oxidize
FADH2
H20
hydrate
NAD
oxidize
NADH
CoA
C14
cleave
16Other Methods
- CPT1 activity measure rate of formation of
pamitoylcarnitine from palmitoyl-CoA and
carnitine (3H) - Carnitine octanoyl transferase (COT)
- Citrate synthase Increased citrate during
exercise
17Table 1
18Figure 1
Palmitate Oxidation
Octanoate Oxidation
Sedentary
Exercise trained
19Figure 2
CPT 1
Citrate Synthase
COT
Sedentary Exercise
20Discussion
LCFA and MCFA increased in endurance-trained
compared to sedentary subjects Adaptations at
the level of transport into mitochondria
(CPT1) Distal processes also involved (b ox
genes?, PPAR?) Increase in MCFA oxidation is not
in agreement with other studies