Lecture 9: Uncouplers of oxidative phosphorylation Flashcards
What are uncouplers?
Uncouplers are transporting ionophores, lipid-soluble weak acids. Their presence on the inner mitochondria membrane increases the membrane’s permeability to protons and provides a route for the dissipation of the electrochemical proton gradient. that doesn’t require ATP synthesis.
Give an example of an uncoupler.
2,4-dinitrophenol. It was prescribed as a slimming agent and caused weight loss then death.
What is another name for the uncoupling protein?
Thermogenin
Which tissue is thermogenin produced in?
Brown adipose tissue of newborn or hibernating mammals.
Why is brown adipose tissue brown?
Due to the huge number of mitochondria, which are brown because they contain cytochrome b.
What is the function of thermogenin?
It blocks the development of a proton electrochemical gradient, thereby stimulating respiration. Delta G (free energy) of respiration is dissipated as heat.
It is important that this heat is released, because newborn mammals can’t shiver (it takes 2-3 years for all muscles to be able to shiver), so depend on this mechanism, which is called ‘non-shivering thermogenesis’.
Although this is costly respiration-wise, providing heat for the organism is very important.
What is thermogenin allosterically activated and inhibited by?
Activated by free fatty acids.
Inhibited by purine nucleotides
What controls the levels of free fatty acids in adipose tissue?
A hormone called noradrenaline.
Describe how thermogenesis is under hormonal control.
1) Noradrenaline binds to a receptor
2) This stimulates adenylate cyclase and levels of cAMP go up
3) cAMP activates cAMP-dependent kinase
4) This kinase phosphorylates triacylglycerol lipase, thus activating it
5) Activated triacylglycerol lipase then hydrolyses triacylglycerols to free fatty acids which activate/open the thermogenin channel.
