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大鼠体内叶绿醇-U-14C和植烷酸-U-14C的代谢

Metabolism of phytol-U-14C and phytanic acid-U-14C in the rat.

作者信息

Mize C E, Avigan J, Baxter J H, Fales H M, Steinberg D

出版信息

J Lipid Res. 1966 Sep;7(5):692-7.

PMID:5971048
Abstract

The metabolism of uniformly-labeled (14)C-phytol, (14)C-phytenic acid, and (14)C-phytanic acid was studied in the rat. Conversion of both phytol and phytenic acid to phytanic acid was demonstrated. Tracer doses of phytol-U-(14)C given orally were well absorbed (30-66%), and approximately 30% of the absorbed dose was converted to (14)CO(2) in 18 hr. After intravenous injection, 20% appeared in (14)CO(2) in 4 hr. Phytanic acid-U-(14)C given intravenously was oxidized at a comparable rate (22-37% in 4 hr) and was as rapidly oxidized as palmitic acid-1-(14)C (21% in 4 hr). Metabolism of these substrates was also studied in rats previously maintained on a diet containing 5% phytol by weight, which causes accumulation of phytanic acid, phytenic acid, and, to a lesser extent, phytol in blood and tissues. Despite the large body pools of preformed, unlabeled substrate in these animals, the fraction of an administered dose of phytol-U-(14)C or phytanic acid-U-(14)C converted to (14)CO(2) was not significantly diminished. These studies indicate that the rat has an appreciable capacity to degrade the highly branched carbon skeleton of phytol and its derivatives. Twenty-four hours after administration of phytol-U-(14)C, the lipid radioactivity remaining in the body was widely distributed among the tissues, highest concentrations being found in liver and adipose tissue. Four hours after intravenous administration of phytanic acid-U-(14)C, all of the major lipid classes in the liver contained radioactivity, most in triglycerides and phospholipids and least in cholesterol esters and lower glycerides. There was no demonstrable incorporation of mevalonate-2-(14)C or acetate-1-(14)C into liver phytanic acid when they were given intravenously to a rat previously fed phytol. Endogenous biosynthesis, if it occurs at all, must be extremely limited.

摘要

在大鼠体内研究了均匀标记的(14)C - 叶绿醇、(14)C - 植酸和(14)C - 植烷酸的代谢情况。证实了叶绿醇和植酸均可转化为植烷酸。经口给予示踪剂量的叶绿醇 - U - (14)C后吸收良好(30 - 66%),在18小时内约30%的吸收剂量转化为(14)CO₂。静脉注射后,4小时内20%出现在(14)CO₂中。静脉注射植烷酸 - U - (14)C后以类似速率被氧化(4小时内为22 - 37%),且氧化速度与棕榈酸 - 1 - (14)C一样快(4小时内为21%)。还在先前喂食含5%(按重量计)叶绿醇饮食的大鼠体内研究了这些底物的代谢情况,这种饮食会导致植烷酸、植酸以及程度较轻的叶绿醇在血液和组织中积累。尽管这些动物体内存在大量预先形成的未标记底物库,但给予的叶绿醇 - U - (14)C或植烷酸 - U - (14)C剂量中转化为(14)CO₂的部分并未显著减少。这些研究表明,大鼠具有相当的能力来降解叶绿醇及其衍生物的高度分支碳骨架。给予叶绿醇 - U - (14)C 24小时后,体内残留的脂质放射性在各组织中广泛分布,肝脏和脂肪组织中的浓度最高。静脉注射植烷酸 - U - (14)C 4小时后,肝脏中所有主要脂质类别都含有放射性,大部分存在于甘油三酯和磷脂中,胆固醇酯和低级甘油酯中最少。当给先前喂食叶绿醇的大鼠静脉注射甲羟戊酸 - 2 - (14)C或乙酸盐 - 1 - (14)C时,未发现它们掺入肝脏植烷酸中。内源性生物合成即使确实发生,也必定极其有限。

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引用本文的文献

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Phytol, a diterpene alcohol from chlorophyll, as a drug against neglected tropical disease Schistosomiasis mansoni.叶绿醇,一种来自叶绿素的二萜醇,作为治疗被忽视的热带病曼氏血吸虫病的药物。
PLoS Negl Trop Dis. 2014 Jan 2;8(1):e2617. doi: 10.1371/journal.pntd.0002617. eCollection 2014.
2
The occurrence of diastereomers of phytanic and pristanic acids and their determination by gas-liquid chromatography.植烷酸和降植烷酸非对映异构体的出现及其气相色谱测定法。
Lipids. 1967 Sep;2(5):357-62. doi: 10.1007/BF02531848.
3
Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.
叶绿醇代谢产物是循环的膳食因子,可激活核受体RXR。
Mol Biol Cell. 1996 Aug;7(8):1153-66. doi: 10.1091/mbc.7.8.1153.
4
Localization of the oxidative defect in phytanic acid degradation in patients with Refsum's disease.雷夫叙姆病患者植烷酸降解氧化缺陷的定位
J Clin Invest. 1969 Jun;48(6):1033-40. doi: 10.1172/JCI106059.
5
Refsum's disease: characterization of the enzyme defect in cell culture.雷夫叙姆病:细胞培养中酶缺陷的特征
J Clin Invest. 1969 Jun;48(6):1017-32. doi: 10.1172/JCI106058.
6
Studies on the metabolic error in Refsum's disease.关于雷夫叙姆病代谢错误的研究。
J Clin Invest. 1967 Mar;46(3):313-22. doi: 10.1172/JCI105533.
7
Tissue distribution of phytanic acid and its analogues in a kinship with Refsum's disease.植烷酸及其类似物在与雷夫叙姆病相关的亲属关系中的组织分布。
Lipids. 1987 Feb;22(2):69-75. doi: 10.1007/BF02534855.