Uncoupling protein

Mitochondrial Uncoupling Protein 2

An uncoupling protein (UCP) is a mitochondrial inner membrane protein that is a proton channel or transporter. An uncoupling protein is thus capable of dissipating the proton gradient generated by NADH-powered pumping of protons from the mitochondrial matrix to the mitochondrial intermembrane space. The energy lost in dissipating the proton gradient via UCPs is not used to do biochemical work. Instead, heat is generated. This is what links UCPhermogenesis. UCPs are positioned in the same membrane as the ATP synthase, which is also a proton channel. The two proteins thus work in parallel with one generating heat and the other generating ATP from ADP and inorganic phosphate, the last step in oxidative phosphorylation.^[1]

There are five types known in mammals:

UCP1, also known as thermogenin
UCP2
UCP3
SLC25A27, also known as "UCP4"
SLC25A14, also known as "UCP5"

Uncoupling proteins play a role in normal physiology, as in cold exposure or hibernation, because the energy is used to generate heat (see thermogenesis) instead of producing ATP. However, other substances, such as 2,4-dinitrophenol and carbonyl cyanide m-chlorophenyl hydrazone, also serve the same uncoupling function, and are considered poisonous. Salicylic acid is also an uncoupling agent and will decrease production of ATP and increase body temperature if taken in excess.^[2] Uncoupling proteins are increased by thyroid hormone, norepinephrine, epinephrine, and leptin.^[3]

References

↑ Nedergaard J, Ricquier D, Kozak LP (2005). "Uncoupling proteins: current status and therapeutic prospects". EMBO Rep. 6 (10): 917–21. doi:10.1038/sj.embor.7400532. PMC 1369193. PMID 16179945.
↑ "California Poison Control System: Salicylates".
↑ Gong DW, He Y, Karas M, Reitman M (1997). "Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, β3-adrenergic agonists, and leptin". J Biol Chem. 272 (39): 24129–32. doi:10.1074/jbc.272.39.24129. PMID 9305858.

External links

Uncoupling Agents at the US National Library of Medicine Medical Subject Headings (MeSH)

Mitochondrial proteins

Outer membrane

fatty acid degradation	Carnitine palmitoyltransferase I Long-chain-fatty-acid—CoA ligase

tryptophan metabolism	Kynureninase

monoamine neurotransmitter metabolism	Monoamine oxidase

Intermembrane space

Inner membrane

oxidative phosphorylation	Coenzyme Q – cytochrome c reductase Cytochrome c NADH dehydrogenase Succinate dehydrogenase

pyrimidine metabolism	Dihydroorotate dehydrogenase

mitochondrial shuttle	Malate-aspartate shuttle Glycerol phosphate shuttle

other	Glutamate aspartate transporter Glycerol-3-phosphate dehydrogenase ATP synthase Carnitine palmitoyltransferase II Uncoupling protein

Matrix

citric acid cycle	Citrate synthase Aconitase Isocitrate dehydrogenase Oxoglutarate dehydrogenase complex Succinyl coenzyme A synthetase Fumarase Malate dehydrogenase

anaplerotic reactions	Aspartate transaminase Glutamate dehydrogenase Pyruvate dehydrogenase complex

urea cycle	Carbamoyl phosphate synthetase I Ornithine transcarbamylase N-Acetylglutamate synthase

alcohol metabolism	ALDH2

PMPCB

Other/to be sorted

steroidogenesis	Cholesterol side-chain cleavage enzyme Steroid 11-beta-hydroxylase Aldosterone synthase Frataxin

Mitochondrial membrane transport protein Mitochondrial permeability transition pore Mitochondrial carrier

Mitochondrial DNA

Complex I	MT-ND1 MT-ND2 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6

Complex III	MT-CYB

Complex IV	MT-CO1 MT-CO2 MT-CO3

ATP synthase	MT-ATP6 MT-ATP8

tRNA	MT-TA MT-TC MT-TD MT-TE MT-TF MT-TG MT-TH MT-TI MT-TK MT-TL1 MT-TL2 MT-TM MT-TN MT-TP MT-TQ MT-TR MT-TS1 MT-TS2 MT-TT MT-TV MT-TW MT-TY

see also mitochondrial diseases

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