Transcript AMP Activated Protein Kinase (AMPK)

AMP Activated Protein Kinase
(AMPK)
an intracellular energy sensor
maintaining the energy balance
AMPK( AMP - dependent/actived protein kinase ) : (單磷
酸腺苷所主導的蛋白質激酶
carnitine palmitoyltransferase-1 (CPT-1):肉鹼棕櫚醯基轉移
酶
5-amino-4-imidazolecarboxamide riboside (AICAR)5-胺基-4咪唑甲醯胺核糖
AMPKK ( AMPK kinase ):(單磷酸腺苷所主導的蛋白質
激酶的激酶 )
acetyl-CoA carboxylase (ACC):乙醯輔酶A羧化酶
malonyl-CoA decarboxylase (MCD)丙二醯輔酶A脫羧酶
If the rate of ATP
consumption exceeds its rate
of production, ADP will
tend to rise and be converted
to AMP by the enzyme
adenylate kinase. The rise in
level of the activating ligand
AMP, coupled with the fall
in level of the inhibitory
nucleotide ATP, activates
AMPK
Glucose Uptake
Contraction and insulin can independently and
additively cause the GLUT-4 transporters to
translocation from below the membranes and
insert into the membrane where they can now
transport glucose into the muscle cell. It is
believed that AMPK plays a part in the
contraction-induced translocation of GLUT-4
transporters1 and has been shown to increase
skeletal muscle glucose uptake
AMPK activation has been shown to decrease
glucose oxidation rates by 50% in rats.
Because of this and other findings, it is
proposed that AMPK's action in restoring
ATP levels in mainly accomplished by
promoting fatty acid oxidation over glucose
oxidation
Fatty acid oxidation
Beta-oxidation of fatty acids (in the form of
fatty acyl-CoA) in the mitochondria supplies a
significant source of ATP regeneration during
exercise, specifically endurance-type exercise.
A protein called carnitine palmitoyltransferase1 (CPT-1), which is found on the outer
membrane of mitochondria, regulates fatty
acid oxidation
Exercise inhibits ACC and rapidly decreases
malonyl-CoA in skeletal muscle. This effect
has been linked to AMPK activation and
increase fatty acid oxidation
Model for the
involvement of AMPK
in the regulation of
skeletal muscle glucose
transport in response to
AICAR, hypoxia,
electrical stimulation
and exercise.
Multiple effects of
AMPK on liver, adipose
tissue, muscle
metabolism, and
pancreatic islets
Postulated mechanisms of
increase in fatty acid
oxidation and on glucose
uptake in skeletal muscle in
response to contraction.
AMPKK, AMP-activated
protein kinase kinase; [5'AMP] and [CP], 5'-AMP
and creatine phosphate
concentrations, respectively;
AMPK-OH and AMPK-OP,
nonphosphorylated and
phosphorylated AMPK,
respectively; ACC, acetylCoA carboxylase; FFA, free
fatty acids.
Two mechanisms for
stimulation of glucose
uptake in skeletal
muscle, one mediated
by insulin and one
triggered by muscle
contraction.
Exercise and electrical
stimulation increase
AMPK activity and
glucose uptake and that
glucose uptake is
increased by chemical
activation of AMPK
AMPK and Exercise
Acute endurance exercise produces short-term
benefits such as increased glucose uptake and
fatty acid oxidation in skeletal muscle.
Long-term participation in endurance exercise
leads to skeletal muscle adaptations, which
occur by altering transcription of exerciseresponsive genes
Chronic endurance training causes many
skeletal muscle adaptations. Some examples
are increased mitochondria and GLUT-4
density, expression of oxidative enzymes, and
increased glycogen storage
Exercise inhibits ACC and rapidly decreases
malonyl-CoA in skeletal muscle. This effect
has been linked to AMPK activation. AICAR
treatment has been shown to deactivate ACC,
reduce malonyl-CoA levels, and increase fatty
acid oxidation.
Activation Of AMPK
Mitochondria Biogenesis
AMPK has been shown to play a role with
mitochondria biogenesis in skeletal muscle. A study
induce an energy-deprived state found that a
significant increase in mitochondrial DNA and
density in skeletal muscle in wild mice, which shows
AMPK is essential component of mitochondria
biogenesis.
An increased number of mitochondria would allow
more total fatty acids to be oxidated by increasing the
body's capacity
Exercise Increases Nuclear AMPK in Human
Skeletal Muscle
SeanL.McGee,
KirstenF.Howlett,
RebeccaL.Starkie, DavidCameron-Smith,
BruceE.Kemp,
and MarkHargreaves1
Acute Exercise Activates AMPK in the Mouse Aorta
JOSE M. CACICEDO, MARIE-SOLEIL GAUTHIER, NATHAN K.
LEBRASSEUR, RAVI JASUJA, NEIL B. RUDERMAN, YASUO IDO
Exercised mouse aortic AMPK and eNOS
phosphorylations both positively correlated
with the net work done by the animals pointing
at a common mechanism of activation
The results also suggest that AMPK is a likely
regulator of eNOS activity induced by exercise.
Brief intense interval exercise activates AMPK and p38 MAPK
signaling and increases the expression of PGC-1 alpha in human
skeletal muscle.
Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M.
an acute session of intense intermittent cycle exercise would activate
signaling cascades linked to mitochondrial biogenesis in human
skeletal muscle
Phosphorylation of AMP-activated protein kinase (AMPK; subunits
alpha1 and alpha2) and the p38 mitogen-activated protein kinase
(MAPK) was higher (P <or= 0.05) immediately after bout 4 vs. preexercise
They concluded that signaling through AMPK and p38 MAPK to
PGC-1alpha may explain in part the metabolic remodeling induced
by low-volume intense interval exercise, including mitochondrial
biogenesis and an increased capacity for glucose and fatty acid
oxidation.
Application
AMPK serves to make one's body more
efficient in producing ATP. It does this by
increasing glucose uptake (GLUT-4
translocation and gene expression) and
insulin sensitivity, promoting fatty acid
oxidation and mitochondria biogenesis, as
well as a host of other effects. The adaptations
caused by AMPK make the body more
efficient in producing ATP and therefore
survival.
The easiest and most economical way to
activate AMPK is through exercise, but
supplement induced activation may prove
useful for those looking to lose weight or
improve different aspects of overall health.
Role of AMPK in Food Intake
a sensor of peripheral energy
balance, is phosphorylated and
activated when energy sources
are low
acts as an intracellular energy
sensor maintaining the energy
balance within the cell
activated AMPK alters
metabolic pathways in muscle
and liver
pharmacological activation of
AMPK in the hypothalamus
increases food intake
A pharmacological activator of AMPK, into
either the third cerebral ventricle or directly
into the paraventricular nucleus of the
hypothalamus significantly increased food
intake.
AMPK plays a role in the regulation of feeding
and identify AMPK as a novel target for antiobesity drugs.
Role of AMPK in regulating
energy balance at the wholebody level. Green arrows
indicate positive effects, and
red lines with bars indicate
negative effects. In the
hypothalamus, activation of
AMPK in response to low
glucose or leptin levels
increases food intake
Anorexigenic Effects of AMPK
Summary
Exercise activates AMPK which in turn inhibits FFA
biosynthesis
An increase AMPK may also change feeding
behavioral
The metabolic role of AMPK is intriguing in both
exercise and health scientists
New substances that activate AMPK will be
researched. Much more research on AMPK is needed
to fully understand its applications and the most
effective methods, besides exercise and diet, to
activate it.
Discussion
How do you use the AMPK knowledge in
order to conduct a research of people suffering
from metabolic syndrome.
In your opinion, in general, who needs to know
how to Activated Protein Kinase and why.
Why APMK influences food intake. Is there
any way that can reverse the situation.