Thermogenin
- OMIM: 113730
- UniProt: P25874
- MGI: 98894
Thermogenin (also uncoupling protein, Eng. Uncoupling protein 1, or UCP1 called ) is a transmembrane protein that is found in the mitochondrial membrane of brown adipose tissue. By its function, heat can be generated without muscle activity such as tremor. The caused by UCP1 thermogenesis is the dominant mode of heat generation in hibernation holding or newborn mammals, including human infants and toddlers.
Mechanism of Action
The molecular mechanism mediated by Thermogenin decoupling is fairly well understood - the function of this ion channel is within the oxidative phosphorylation provides an additional path for the re-entry of protons into the mitochondrial matrix. Thermogenin is activated, it closes the proton cycle short, which couples the respiratory chain to the ATP synthase complex, which is adenosine triphosphate ( ATP) provides the energy balance of the cell. By Thermogenin this coupling is released, the energy produced by cellular respiration is directly implemented without the formation of the energy storage ATP in heat (dissipation ).
Thermogenin is related to other mitochondrial metabolic transporters such as the adenine nucleotide transporter, a proton channel in the inner mitochondrial membrane, which mediates the transport of protons from the membrane space in the mitochondrial matrix.
UCP1 is found only in brown adipose tissue. By attending this tissue acquires its tremendous ability to generate heat.
UCP1 is activated by fatty acids in the following way: in the sympathetic nervous system norepinephrine is released, binds to the β3 - adrenergic receptor in the cell membrane of brown fat cells. Characterized an adenylyl cyclase is activated, which catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). cAMP in turn activates protein kinase A, the active C subunits detach from the regulatory R subunits. The active protein kinase A in turn activated by phosphorylation a lipase. This lipase catalyzes the conversion of triglycerides into free fatty acids that eventually activate UCP1, lifting its inhibition by purine nucleotides (GDP, ADP). Thermogenesis is ended, that the mitochondria oxidize free fatty acid residues. This UCP1 inactive and the cell returns to normal cell breathing, is synthesized in the ATP.
Discovery history
The enzyme was discovered in 1979 as an Uncoupling Protein, 1988, was cloned for the first time.
A homologous to Thermogenin gene was identified in 1997 and UCP2 was called. In the last decade three homologues UCP1 have been found, including UCP3, UCP4, and BMCP1 (also known as UCP5 ).