維生素-K（血凝和骨代謝中的一個(gè)重要因子）主要以來(lái)自植物的葉綠醌(PK)的形式存在于飲食中。這種維生素的一種形式,，即甲萘醌-4或MK-4,，在人類和大鼠的大腦、腎臟和胰腺中有高特異性的組織分布,，說(shuō)明葉綠醌是局部合成的,。
現(xiàn)在，催化這種合成的一種酶已被識(shí)別出來(lái)：“含有1的UbiA異戊烯轉(zhuǎn)移酶” (UBIAD1)是大腸桿菌的一種酶的人類同源物,。以前其功能不清楚,，盡管它在“施奈德結(jié)晶狀角膜營(yíng)養(yǎng)不良”中是一個(gè)候選基因。
關(guān)于一種人類MK-4酶能夠生物合成維生素-K的荷爾蒙活性形式的發(fā)現(xiàn),，對(duì)于有關(guān)人類維生素-K需求及骨健康的研究工作將有參考價(jià)值,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi:10.1038/nature09464
Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme
Kimie Nakagawa,Yoshihisa Hirota,Natsumi Sawada,Naohito Yuge,Masato Watanabe,Yuri Uchino,Naoko Okuda,Yuka Shimomura,Yoshitomo Suhara& Toshio [email protected]
Vitamin?K occurs in the natural world in several forms, including a plant form, phylloquinone (PK), and a bacterial form, menaquinones (MKs). In many species, including humans, PK is a minor constituent of hepatic vitamin?K content, with most hepatic vitamin?K content comprising long-chain MKs. Menaquinone-4 (MK-4) is ubiquitously present in extrahepatic tissues, with particularly high concentrations in the brain, kidney and pancreas of humans and rats1, 2, 3. It has consistently been shown that PK is endogenously converted to MK-4 (refs 4–8). This occurs either directly within certain tissues or by interconversion to menadione (K3), followed by prenylation to MK-4 (refs 9–12). No previous study has sought to identify the human enzyme responsible for MK-4 biosynthesis. Previously we provided evidence for the conversion of PK and K3 into MK-4 in mouse cerebra13. However, the molecular mechanisms for these conversion reactions are unclear. Here we identify a human MK-4 biosynthetic enzyme. We screened the human genome database for prenylation enzymes and found UbiA prenyltransferase containing 1 (UBIAD1), a human homologue of Escherichia coli prenyltransferase menA. We found that short interfering RNA against the UBIAD1 gene inhibited the conversion of deuterium-labelled vitamin?K derivatives into deuterium-labelled-MK-4 (MK-4-d7) in human cells. We confirmed that the UBIAD1 gene encodes an MK-4 biosynthetic enzyme through its expression and conversion of deuterium-labelled vitamin?K derivatives into MK-4-d7 in insect cells infected with UBIAD1 baculovirus. Converted MK-4-d7 was chemically identified by 2H-NMR analysis. MK-4 biosynthesis by UBIAD1 was not affected by the vitamin?K antagonist warfarin. UBIAD1 was localized in endoplasmic reticulum and ubiquitously expressed in several tissues of mice. Our results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin?K intake and bone health.
