在這周出版的《生物化學(xué)雜志》(JBC)中,有一篇文章報道紅辣椒粉不僅能給人帶來熱辣的感覺,其中的活性化合物能直接誘導(dǎo)發(fā)熱,,在該過程中細胞將能量直接轉(zhuǎn)化為熱量。
辣椒素(Capsaicin,CPS)是紅辣椒粉中含有的一種化合物,,它能帶來辛辣的感覺;CPS能刺激一種在嗅感覺神經(jīng)中發(fā)現(xiàn)的受體,,然后引起熱辣的感覺并帶來發(fā)紅和出汗的反應(yīng),。
最近,Yasser Mahmoud發(fā)現(xiàn)辣椒素通過改變一種名為SERCA的肌蛋白的活性,,以更直接的方式產(chǎn)“熱”,。一般情況下,肌肉收縮會伴隨一個鈣離子釋放高峰,,鈣離子從肌漿網(wǎng)(sarcoplasmic reticulum, SR)區(qū)域釋放出來,,然后SERCA再將鈣離子泵回SR(利用ATP能量),使肌肉松弛,,循環(huán)發(fā)生該過程,。
但是,CPS能與SERCA結(jié)合并使其“泵”的活性“解耦合”,,這樣就使蛋白質(zhì)繼續(xù)燃燒ATP能量,,但卻不是用于泵回鈣離子。因此,,所有的ATP能量都作為熱量而散發(fā),。這種解耦合就是生熱反應(yīng),它是維持體溫的一種重要方式,,常見于冬眠動物,。Mahmoud指出,辣椒素是第一種已知的能夠增強產(chǎn)熱過程的天然化合物,。
這些發(fā)現(xiàn)進一步解釋了攝入辣椒素后能提高代謝速度和體溫的原因,。盡管這些研究需要的辣椒素數(shù)量非常之大(可能多于任何人能食用的量),但可以利用辣椒素的結(jié)構(gòu)作為模型,,設(shè)計可用于臨床上治療低溫癥的潛在化合物,。(生物谷Bioon.com)
生物谷推薦原始出處:
JBC,doi:10.1074/jbc.M803654200,,Yasser Ahmed Mahmmoud
Capsaicin stimulates uncoupled ATP hydrolysis by sarcoplasmic reticulum calcium pump
Yasser Ahmed Mahmmoud
Institute of Physiology and Biophysics, University of Aarhus, Aarhus C DK-8000
Corresponding Author: [email protected]
In muscle cells, the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) couples the free energy of ATP hydrolysis to pump Ca2+ ions from the cytoplasm to the SR lumen. In addition, SERCA plays a key role in non-shivering thermogenesis through uncoupled reactions, where ATP hydrolysis takes place without active Ca2+ translocation. Capsaicin (CPS) is a naturally occurring vanilloid, the consumption of which is linked with increased metabolic rate and core body temperature. Here, we document the stimulation by CPS of the Ca2+-dependent ATP hydrolysis by SERCA without effects on Ca2+ accumulation. The stimulation by CPS was significantly dependent on the presence of a Ca2+ gradient across the SR membrane. ATP activation assays showed that the drug reduced the nucleotide affinity at the catalytic site whereas the affinity at the regulatory site increased. Several biochemical analyses indicated that CPS stabilizes an ADP-insensitive E2P related conformation that dephosphorylates at a higher rate than the control enzyme. Under conditions where uncoupled SERCA was specifically inhibited by the treatment with fluoride, low temperatures, or dimethyl sulfoxide, CPS had no stimulatory effect on ATP hydrolysis by SERCA. It is concluded that CPS stabilizes a SERCA sub-conformation where Ca2+ is released from the phosphorylated intermediate to the cytoplasm instead of the SR lumen, increasing ATP hydrolysis not coupled with Ca2+ transport. To the best of our knowledge, CPS is the first natural drug that augments uncoupled SERCA, presumably resulting in thermogenesis. The role of CPS as a SERCA modulator is discussed. Bioon.com