Thermogenin
From Wikipedia, the free encyclopedia
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uncoupling protein 1 (mitochondrial, proton carrier)
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| Identifiers | |
| Symbol | UCP1 UCP |
| HUGO | 12517 |
| Entrez | 7350 |
| OMIM | 113730 |
| RefSeq | NM_021833 |
| UniProt | P25874 |
| Other data | |
| Locus | Chr. 4 q31 |
Thermogenin (also known as uncoupling protein 1, or UCP1) is an uncoupling protein found in the mitochondria of brown adipose tissue (BAT). It is used to generate heat by non-shivering thermogenesis. Non-shivering thermogenesis is the primary means of heat generation in hibernating mammals and in human infants.
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[edit] Mechanism
Though some details remain controversial, the molecular mechanism of thermogenin mediated uncoupling is reasonably well understood; thermogenin provides an alternative pathway by which protons can reenter the mitochondrial matrix, allowing the energy stored by proton pumping to be dissipated in the form of heat. Like the ATP synthase, thermogenin is a proton channel in the mitochondrial inner membrane that permits the translocation of protons from the mitochondrial intermembrane space to the mitochondrial matrix. Unlike ATP synthase however, which ‘couples’ proton translocation to synthesis of ATP, thermogenin catalyzes a ‘wasteful’ proton leak across the mitochondrial inner membrane. It is termed an uncoupling protein because it ‘uncouples’ the mitochondrial proton gradient from the generation of ATP by ATP synthase. This mechanism is regulated by hormones.
An external signal causes the secretion of norepinephrine which binds to a membrane receptor. This binding activates adenylyl cyclase which catalyses the conversion of ATP to cyclic AMP (cAMP). cAMP activates protein kinase A causing its active C subunits to be freed from its regulatory R subunits. Active protein kinase A phosphorylates triacylglycerol lipase, thereby activating it. The lipase converts triacylglycerols into free fatty acids which activate thermogenin, overriding the inhibition set in place by ATP, ADP and Pi. Thermogenin is opened and protons flow through dissipating the proton gradient.
[edit] History
Thermogenin was discovered in 1979[1] and was first cloned in 1988.[2][3]
Uncoupling protein two (UCP2), a homolog of thermogenin, was identified in 1997.
In the past decade three additional homologs of thermogenin have been identified, including UCP3, UCP4, and BMCP1 (also known as UCP5).
[edit] References
- ^ Nicholls D, Bernson V, Heaton G. "The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation". Experientia Suppl 32: 89-93. PMID 348493.
- ^ http://www.jbc.org/cgi/reprint/263/25/12274
- ^ Bouillaud F, Raimbault S, Ricquier D (1988). "The gene for rat uncoupling protein: complete sequence, structure of primary transcript and evolutionary relationship between exons". Biochem Biophys Res Commun 157 (2): 783-92. PMID 3202878. link
[edit] External links
- Seaweed anti-obesity tablet hope (BBC - Thermogenin mentioned as part of process)
- MeSH thermogenin
