Thermogenin

uncoupling protein 1 (mitochondrial, proton carrier)
Properties of human protein
Mass / length primary structure	307 amino acids
Secondary to quaternary structure	multipass membrane protein
Identifier
Gene names	UCP1 ; SLC25A7; UCP; Thermogenin
External IDs	OMIM : 113730 ; UniProt : P25874 ; MGI : 98894 ;
Transporter classification
TCDB	2.A.29.3.2
designation	Mitochondrial carrier
Occurrence
Homology family	mitochondrial carrier
Parent taxon	Eukaryotes
	Orthologue

Thermogenin (also uncoupling protein , engl. Uncoupling Protein 1 or UCP1 called) is a transmembrane protein , located in the mitochondrial membrane of brown adipose tissue is. Its function allows heat to be generated without muscle activity such as tremors. Thermogenesis induced by UCP1 is the predominant mode of heat generation in hibernating or newborn mammals, including human infants and young children. Thermogenin is one of the uncoupling proteins .

Mechanism of action

Activation process: In the last step of the cascade triggered by norepinephrine, an existing inhibition of thermogenin by free fatty acids is lifted. P : phosphate residue, ve + : charge transfer

The molecular mechanism of thermogenin-mediated decoupling is well understood - the function of this ion channel provides an additional path for protons to re- enter the mitochondrial matrix within oxidative phosphorylation . If thermogenin is activated, it closes the proton cycle - similar to 2,4-dinitrophenol - which couples the respiratory chain to the ATP synthase complex, which supplies the adenosine triphosphate (ATP) for the energy balance of the cell: it becomes thermogenin Coupling is canceled and the energy gained through cellular respiration is converted directly into heat ( dissipation ) without the formation of the energy store ATP .

Thermogenin is related to other mitochondrial metabolic transporters such as the adenine nucleotide transporter, a proton channel in the inner mitochondrial membrane that mediates the transport of protons from the membrane space into the mitochondrial matrix.

UCP1 occurs exclusively in brown adipose tissue. Its presence gives this tissue its enormous ability to generate heat.

UCP1 is fatty acids activated in the following way: in the sympathetic nervous system is norepinephrine released, which the β3-adrenoceptor in the cell membrane of brown fat cells bind. This activates an adenylyl cyclase that catalyzes the conversion of ATP to cyclic adenosine monophosphate (cAMP). In turn, cAMP activates protein kinase A , the active C subunits of which separate from the regulatory R subunits. The active protein kinase A in turn activates a lipase through phosphorylation . This lipase catalyzes the conversion of triglycerides into free fatty acids, which ultimately activate UCP1 by removing its inhibition by purine nucleotides ( GDP , ADP ). Thermogenesis is ended when the mitochondria oxidize free fatty acid residues. This makes UCP1 inactive and the cell reverts to normal cellular respiration, during which ATP is synthesized.

Discovery story

The ion channel was discovered in 1979 as an uncoupling protein , and in 1988 it was cloned for the first time.

A gene homologous to thermogenin was identified in 1997 and was named UCP2. Three more UCP1 homologues have been found in the past decade, including UCP3, UCP4, and BMCP1 (also known as UCP5).

literature

David Nelson, Michael Cox: Lehninger Principles of Biochemistry . 4th edition. WH Freeman, New York 2005, ISBN 0-7167-4339-6
Ricquier D, Bouillaud F: The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP . In: Biochem. J. . 345 Pt 2, 2000, pp. 161-79. PMID 10620491 .
Muzzin P: The uncoupling proteins . In: Ann. Endocrinol. (Paris) . 63, No. 2 Pt 1, 2002, pp. 106-10. PMID 11994670 .
Del Mar Gonzalez-Barroso M, Ricquier D, Cassard-Doulcier AM: The human uncoupling protein-1 gene (UCP1): present status and perspectives in obesity research . In: Obesity Reviews . 1, No. 2, 2002, pp. 61-72. PMID 12119988 .
Cassard AM, Bouillaud F, Mattei MG, et al. : Human uncoupling protein gene: structure, comparison with rat gene, and assignment to the long arm of chromosome 4 . In: J. Cell. Biochem. . 43, No. 3, 1990, pp. 255-64. doi : 10.1002 / jcb.240430306 . PMID 2380264 .
Bouillaud F, Villarroya F, Hentz E, et al. : Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe . In: Clin. Sci. . 75, No. 1, 1988, pp. 21-7. PMID 3165741 .
Oppert JM, Vohl MC, Chagnon M, et al. : DNA polymorphism in the uncoupling protein (UCP) gene and human body fat . In: Int. J. Obes. Relat. Metab. Disord. . 18, No. 8, 1994, pp. 526-31. PMID 7951471 .
Clément K, Ruiz J, Cassard-Doulcier AM, et al. : Additive effect of A → G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in morbid obesity . In: Int. J. Obes. Relat. Metab. Disord. . 20, No. 12, 1997, pp. 1062-6. PMID 8968850 .
Schleiff E, Shore GC, Goping IS: Human mitochondrial import receptor, Tom20p. Use of glutathione to reveal specific interactions between Tom20-glutathione S-transferase and mitochondrial precursor proteins . In: FEBS Lett . . 404, No. 2-3, 1997, pp. 314-8. doi : 10.1016 / S0014-5793 (97) 00145-2 . PMID 9119086 .
Urhammer SA, Fridberg M, Sørensen TI, et al. : Studies of genetic variability of the uncoupling protein 1 gene in Caucasian subjects with juvenile-onset obesity . In: J. Clin. Endocrinol. Metab. . 82, No. 12, 1998, pp. 4069-74. PMID 9398715 .
Jezek P, Urbánková E: Specific sequence of motifs of mitochondrial uncoupling proteins . In: IUBMB Life . 49, No. 1, 2000, pp. 63-70. PMID 10772343 .
Mori H, Okazawa H, Iwamoto K, et al. : A polymorphism in the 5 'untranslated region and a Met229 → Leu variant in exon 5 of the human UCP1 gene are associated with susceptibility to type II diabetes mellitus . In: Diabetologia . 44, No. 3, 2001, pp. 373-6. doi : 10.1007 / s001250051629 . PMID 11317671 .
Nibbelink M, Moulin K, Arnaud E, et al. : Brown fat UCP1 is specifically expressed in uterine longitudinal smooth muscle cells . In: J. Biol. Chem. . 276, No. 50, 2002, pp. 47291-5. doi : 10.1074 / jbc.M105658200 . PMID 11572862 .
Echtay KS, Roussel D, St-Pierre J, et al. : Superoxide activates mitochondrial uncoupling proteins . In: Nature . 415, No. 6867, 2002, pp. 96-9. doi : 10.1038 / 415096a . PMID 11780125 .
Rousset S, del Mar Gonzalez-Barroso M, Gelly C, et al. : A new polymorphic site located in the human UCP1 gene controls the in vitro binding of CREB-like factor . In: Int. J. Obes. Relat. Metab. Disord. . 26, No. 5, 2002, pp. 735-8. doi : 10.1038 / sj.ijo.0801973 . PMID 12032762 .
Rim JS, Kozak LP: Regulatory motifs for CREB-binding protein and Nfe2l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene . In: J. Biol. Chem. . 277, No. 37, 2002, pp. 34589-600. doi : 10.1074 / jbc.M108866200 . PMID 12084707 .
Kieć-Wilk B, Wybrańska I, Malczewska-Malec M, et al. : Correlation of the -3826A> G polymorphism in the promoter of the uncoupling protein 1 gene with obesity and metabolic disorders in obese families from southern Poland . In: J. Physiol. Pharmacol. . 53, No. 3, 2003, pp. 477-90. PMID 12375583 .
Strausberg RL, Feingold EA, Grouse LH, et al. : Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . In: Proc. Natl. Acad. Sci. USA . 99, No. 26, 2003, pp. 16899-903. doi : 10.1073 / pnas.242603899 . PMID 12477932 .

Web links

Individual evidence

↑ Entrez gene: UCP1 uncoupling protein 1 (mitochondrial, proton carrier) . Retrieved February 25, 2011.
↑ Nicholls DG, Bernson VS, Heaton GM: The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation . In: Experientia Suppl . 32, 1978, pp. 89-93. PMID 348493 .
↑ Kozak LP, Britton JH, Kozak UC, Wells JM: The mitochondrial uncoupling protein gene. Correlation of exon structure to transmembrane domains . In: J. Biol. Chem. . 263, No. 25, 1988, pp. 12274-7. PMID 3410843 .
↑ Bouillaud F, Raimbault S, Ricquier D: The gene for rat uncoupling protein: complete sequence, structure of primary transcript and evolutionary relationship between exons . In: Biochem. Biophys. Res. Commun. . 157, No. 2, 1988, pp. 783-92. doi : 10.1016 / S0006-291X (88) 80318-8 . PMID 3202878 .

[entrez-1] Entrez gene: UCP1 uncoupling protein 1 (mitochondrial, proton carrier) . Retrieved February 25, 2011.

[pmid348493-2] Nicholls DG, Bernson VS, Heaton GM: The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation . In: Experientia Suppl . 32, 1978, pp. 89-93. PMID 348493 .

[pmid3410843-3] Kozak LP, Britton JH, Kozak UC, Wells JM: The mitochondrial uncoupling protein gene. Correlation of exon structure to transmembrane domains . In: J. Biol. Chem. . 263, No. 25, 1988, pp. 12274-7. PMID 3410843 .

[pmid3202878-4] Bouillaud F, Raimbault S, Ricquier D: The gene for rat uncoupling protein: complete sequence, structure of primary transcript and evolutionary relationship between exons . In: Biochem. Biophys. Res. Commun. . 157, No. 2, 1988, pp. 783-92. doi : 10.1016 / S0006-291X (88) 80318-8 . PMID 3202878 .