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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

2
Beta 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

3
Fed 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
4
FASTED STATE
CPT1
FFA
FA-CoA
FA-CoA
(-)
box
(-)
Malonyl CoA
()
ACC
Acetyl CoA
Acetyl CoA
citrate
citrate
TCA
liver
Ketone bodies
blood
cytosol
mitochondria
5
Skeletal 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
6
Substrate shift
  • Increase fatty acid oxidation
  • Decrease carbohydrate oxidation
  • Decrease glycolysis
  • How does this occur?

7
Energy expenditure increases with exercise
intensity
Muscle glycogen
Triglycerides
Plasma FFA
Plasma glucose
8
Moderate Exercise
Increased lipolysis (epi activates
HSL) Increased FA release Increased blood
flow Increased FA oxidation in muscle Increased
accumulation of acetyl CoA
9
The 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
10
Fed state
Fasted or Exercise
Glucose availability
Increased b oxidation
cytosolic citrate
(-)
()
(-)
(-)
(-)
Malonyl CoA
b Ox
PFK
ACC
Glycolysis
11
Muscle 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
12
Long- 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
13
Hypothesis
  • 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?

14
Methods
Percutaneous needle biopsy
Vastus lateralis
15
C14
a
b
g
palmitate
FAD
oxidize
FADH2
H20
hydrate
NAD
oxidize
NADH
CoA
C14
cleave

16
Other 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

17
Table 1
18
Figure 1

Palmitate Oxidation

Octanoate Oxidation
Sedentary
Exercise trained
19
Figure 2

CPT 1

Citrate Synthase
COT
Sedentary Exercise
20
Discussion
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
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