Lecture 4 - Intracellular signalling Flashcards
At the level of gene transcription and protein translation, what causes signalling in muscle?
Mechanical load
Hormonal adjustment
Neuronal activation
Metabolic disturbance
describe Ca2+ - calmodulin (CaM) signalling in muscle
increase in calcium when muscles depolarise - Ca2+ combines with a protein called calmodulin and there is a kinase (cAMP kinase) - there are various isoforms of this kinase but the most predominant one is cAMP 2
Generally speaking, what does CAMKinase 2 have the ability to modify?
modify other proteins
modify the nucleus to change gene expression - part of the adaptive response
CaM can also target phosphorylase kinase causing?
glycolysis, but also turns off protein synthesis
after exercise this is reversed, which helps recovery
Exercise ______ Calcium-calmodulin-dependent protein kinase activity in human skeletal muscle
increases
AMP-activated protein kinase is activated by …
AMP - an energy sensor
What are the effects of AMP-activated protein kinase on the heart?
stimulates: glucose uptake, glycolysis, FA oxidation
What are the effects of AMP-activated protein kinase on the hypothalamus
stimualtes Food intake
What are the effects of AMP-activated protein kinase on the skeletal muscle
stimualtes FA oxidation, glucose uptake, expression of GLUT4, MItochondria
What are the effects of AMP-activated protein kinase on the adipose tissue
Inhibits: FA synthesis, lipolysis
energy consuming pathways
What are the effects of AMP-activated protein kinase on the Liver
Inhibits: FA synthesis Cholesterol synthesis, Gluconeogenesis
What are the effects of AMP-activated protein kinase on the Pancreas
inhibits Insulin secretion
Activation of the other metabolic pathways is very good at…
maintaining ATP levels
AMPK activity is directly correlated with…
the exercise intensity
How is GLUT 4 expression increased during exercise?
When muscle contract they consume energy
they break down ATP, creatine P, glyocgen - which gives you an inccrease in AMP = > this activates AMP-kinase
Ca2+ increase also activates CaM Kinase 2
These two enzymes can phosphorylate a transcriptional repressor which comes out of the nucleus, the transcriptional factor (MEF2) binds to the GLUT 4 promoter and increases GLUT transcription/translation