St. Jude兒童研究醫(yī)院研究者發(fā)現(xiàn),，ABCB6蛋白對(duì)于一種分子的產(chǎn)生起著關(guān)鍵作用，這種分子對(duì)于紅細(xì)胞攜帶氧,，肝細(xì)胞破壞毒素以及細(xì)胞從攝取營養(yǎng)物質(zhì)后排放能量方面發(fā)揮重要的作用,。
??St. Jude研究者指出，ABCB6蛋白寄宿在“能量動(dòng)力站”--線粒體的外膜,；它將一種重要的生命分子--比咯滋質(zhì)輸入線粒體,。這些研究結(jié)果已經(jīng)在線出版在《自然》雜志上。
??在線粒體內(nèi)部,，比咯紫質(zhì)被轉(zhuǎn)換成亞鐵血紅素,。亞鐵血紅素是血紅蛋白攜帶氧的血素部分。同時(shí)也是某些破壞毒素的肝臟酶的關(guān)鍵組分,；在線粒體中,，亞鐵血紅素被稱為是氧氣產(chǎn)生能量分子的“呼吸鏈”酶。
??ABCB6蛋白定位和功能的新發(fā)現(xiàn)為比咯紫質(zhì)是如何進(jìn)入線粒體轉(zhuǎn)變成亞鐵血紅素這樣一個(gè)長期疑惑作了很好的解答,。St. Jude藥學(xué)成員John Schuetz博士認(rèn)為,，比咯紫質(zhì)帶負(fù)電荷，所以能進(jìn)入線粒體內(nèi)部,，一個(gè)磁場的兩個(gè)負(fù)極應(yīng)該互相排斥,，但一個(gè)負(fù)電荷分子是如何進(jìn)入一個(gè)負(fù)電荷環(huán)境不是很清楚。John Schuetz等的研究工作表明,，ABCB6只是通過抓住比咯紫質(zhì)分子，將其帶入線粒體,，從而克服了以上問題,。
??“我們指出，ABCB6和亞鐵血紅素,、比咯紫質(zhì)水平之間的動(dòng)態(tài)聯(lián)系有助于調(diào)節(jié)亞鐵血紅素的產(chǎn)量,。” Schuetz說。研究小組發(fā)現(xiàn),，線粒體膜上ABCB6蛋白的增加導(dǎo)致細(xì)胞產(chǎn)生更多的亞鐵血紅素必須的比咯紫質(zhì),。他們之間這種聯(lián)系的任何中斷都可能會(huì)因?yàn)閬嗚F血紅素或者比咯紫質(zhì)的改變而給細(xì)胞帶來嚴(yán)重的問題。
??有了這些新的研究資料,，將有助于研究者更好地從分子水平研究某些疾病,，對(duì)疾病的成因了解更多,，從而可能知道如何阻止或治療這些疾病。有一類疾病是皮膚性卟啉病,，這是由于比咯紫質(zhì)的增加引起皮膚起水皰,，在太陽下就會(huì)腫脹；急性的卟啉病激發(fā)胸,，腹部,，四肢或背部的痛疼，麻痹,，抽筋和個(gè)性的變化以及精神的紊亂等神經(jīng)問題,。Schuetz認(rèn)為，如果卟啉病人吃了某些干擾其系統(tǒng)的鎮(zhèn)定劑和其他藥物,，病人會(huì)突然急性發(fā)作,，所以Schuetz的工作為‘生產(chǎn)亞鐵血紅素生化途徑的中斷是如何引起各種疾病’提供了一個(gè)總的描繪。
英文原文：
ABCB6 is key to production of heme in hemoglobin
Investigators at St. Jude Children's Research Hospital have discovered that a protein called ABCB6 plays a central role in production of a molecule that is key to the ability of red blood cells to carry oxygen, of liver cells to break down toxins, and of cells to extract energy from nutrients.
The St. Jude investigators showed that ABCB6 is lodged within the outer membrane of the cell's energy powerhouse called the mitochondria; and that it ferries into mitochondria a type of molecule called a porphryin, a molecule essential for life. A report on these results appears in the advanced online publication of Nature.
Inside the mitochondrion, porphyrins are converted to heme. Heme is the oxygen-carrying part of the red blood cell molecule called hemoglobin, as well as a critical part of certain liver enzymes that break down toxins, and so-called "respiratory chain" enzymes in mitochondria that use oxygen to produce energy-rich molecules.
The discovery of the location and function of ABCB6 solved the long-standing riddle of how porphyrins get into mitchondria so they can be used to make heme, said John Schuetz, PhD, a member of St. Jude Pharmaceutical Sciences. "Porphyrins are negatively charged and so is the inside of mitochondria," Schuetz said. "So it wasn't clear how a negatively charged molecule could get into a negatively charged environment when it should have been repulsed--like two negative poles of a magnet pushing each other apart. Our work showed that ABCB6 overcomes that problem by simply grabbing porphyrin molecules and pulling them in.
"We showed that there is a dynamic relationship between ABCB6 and the levels of heme and porphyrin that helps to regulate the production of heme," Schuetz said. The team found that the increase in ABCB6 in mitochondrial membranes caused the cells to make more porphyrin, the building block of heme. "Any disruption of this relationship can cause serious problems in the cell by altering levels of heme or porphyrins," Schuetz said.
Armed with this new information, researchers will be better able to study certain diseases at the molecular level and learn more about their causes and perhaps how to prevent or treat them. One such group of diseases is cutaneous porphyria, a buildup of porphyrins that causes the skin to blister and swell in sunlight; and acute porphoryia, a nerve problem that triggers pain in the chest, abdomen, limbs or back, as well as paralysis, cramping and personality changes or mental disorders. "Also, people with porphyria can suffer sudden, acute attacks if they take certain tranquilizers and other drugs that interfere with this system," Schuetz said. "So our work contributes to the overall picture of how disruption of the biochemical pathway of heme production can cause a variety of serious diseases."
