Ahmed A A, McCarthy R D, Porter G A
Atherosclerosis. 1979 Apr;32(4):347-57. doi: 10.1016/0021-9150(79)90002-9.
Two preparations active in reducing hepatic cholesterol biosynthesis were isolated from bovine skim milk. One of the inhibitors was in the dialysate and was identified as orotic acid (OA). The other inhibitor, present in the retentate, was not identified. Orotic acid appears to act by inhibiting cholesterol biosynthesis before the formation of mevalonate, whereas the retentate inhibitor exerts its effect beyond the formation of mevalonate in the biosynthetic pathway. Human milk also inhibited the incorporation of both labeled acetate and mevalonate into cholesterol by rat liver. Orotic acid was not detectable in human milk samples employed in this study. Administration of [6-14C]orotate to rats revealed its conversion to uracil in the liver. Subsequent work demonstrated that uracil had inhibitory activity on hepatic cholesterol biosynthesis similar to that of orotate when incubated with rat liver slices.
从牛乳中分离出两种具有降低肝脏胆固醇生物合成活性的制剂。其中一种抑制剂存在于透析液中，被鉴定为乳清酸（OA）。另一种抑制剂存在于截留物中，尚未被鉴定。乳清酸似乎是通过在甲羟戊酸形成之前抑制胆固醇生物合成来发挥作用的，而截留物抑制剂在生物合成途径中甲羟戊酸形成之后发挥其作用。人乳也抑制大鼠肝脏将标记的乙酸盐和甲羟戊酸掺入胆固醇。在本研究中使用的人乳样本中未检测到乳清酸。给大鼠施用[6-¹⁴C]乳清酸盐显示其在肝脏中转化为尿嘧啶。随后的研究表明，当与大鼠肝切片一起孵育时，尿嘧啶对肝脏胆固醇生物合成具有与乳清酸盐类似的抑制活性。
