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辅酶Q10的代谢:豚鼠的胆汁和尿液排泄研究。

Metabolism of coenzyme Q10: biliary and urinary excretion study in guinea pigs.

作者信息

Nakamura T, Ohno T, Hamamura K, Sato T

机构信息

Eisai Research Laboratories, Eisai Co., Ltd., Tokyo, Japan.

出版信息

Biofactors. 1999;9(2-4):111-9. doi: 10.1002/biof.5520090205.

Abstract

Biliary and urinary metabolites were examined after intravenous administration of 14C-coenzyme Q10 (14C-CoQ) to guinea pigs. Cumulative recovery of administered radioactivity for up to 8 hours by bile drainage was 4.8%. The greater part of radioactivity was detected in conjugate form. After hydrolyzing with beta-glucuronidase, aglycone fragments were subjected to methylation and reductive acetylation. The main metabolite was demonstrated to be Q acid-1 1,4-hydroquinone diacetate methyl ester (M-1) on HPLC. Then, the main metabolite was assumed to be glucuronide of 2,3-dimethoxy-5-methyl-6-(3'-methyl-5'-carboxy-2'-pentenyl)-1, 4-benzohydroquinone [Q acid-I hydroquinone]. The cumulative urinary recovery of the administered radioactivity over 48 hours was 8.3%. The labeled samples were treated similarly to bile. The urinary metabolites of CoQ10 consisted of unconjugated and conjugated forms. Lyophilized urine was treated as a bile sample and analyzed. The two major metabolites were assigned to be M-1 and Q acid-II 1,4-hydroquinone diacetate methyl ester (M-2). Then, the two metabolites were assumed to be composed of Q acid-I and 2,3-dimethoxy-5-methyl-6-(3'-carboxypropyl)-1,4-benzoquinone (Q acid-II) in free and corresponding hydroquinone conjugate forms. To investigate the effect of exogenous labeled CoQ10 on unlabeled CoQ10 (endogenous) metabolites in urine, simultaneous quantitative determination was performed using deuterium labeled CoQ10 (CoQ10-d5). Urine collected over a 72-hour period after intravenous administration of CoQ10-d5 was processed similarly to that described above and two derivatized metabolites (M-1 and M-2) were quantified by gas chromatography-mass fragmentography with the multi-ion detection method. The analytical results showed that the addition of exogenous labeled CoQ10 did not influence the metabolism (or breakdown) of unlabeled (endogenous) CoQ10.

摘要

给豚鼠静脉注射14C - 辅酶Q10(14C - CoQ)后,对胆汁和尿液中的代谢产物进行了检测。通过胆汁引流,长达8小时的给药放射性累积回收率为4.8%。大部分放射性以结合形式被检测到。用β - 葡萄糖醛酸酶水解后,对苷元片段进行甲基化和还原乙酰化处理。在高效液相色谱法(HPLC)上,主要代谢产物被证明是Q酸 - 1 1,4 - 对苯二酚二乙酸甲酯(M - 1)。然后,推测主要代谢产物是2,3 - 二甲氧基 - 5 - 甲基 - 6 - (3' - 甲基 - 5' - 羧基 - 2' - 戊烯基) - 1,4 - 苯并对苯二酚[Q酸 - I对苯二酚]的葡萄糖醛酸苷。给药放射性在48小时内的尿液累积回收率为8.3%。对标记样品的处理方式与胆汁类似。辅酶Q10的尿液代谢产物由未结合和结合形式组成。将冻干尿液作为胆汁样品进行处理并分析。两种主要代谢产物被确定为M - 1和Q酸 - II 1,4 - 对苯二酚二乙酸甲酯(M - 2)。然后,推测这两种代谢产物分别由游离形式和相应对苯二酚结合形式的Q酸 - I和2,3 - 二甲氧基 - 5 - 甲基 - 6 - (3' - 羧基丙基) - 1,4 - 苯醌(Q酸 - II)组成。为了研究外源性标记的辅酶Q10对尿液中未标记的辅酶Q10(内源性)代谢产物的影响,使用氘标记的辅酶Q10(CoQ10 - d5)进行了同步定量测定。静脉注射CoQ10 - d5后72小时内收集的尿液按照上述类似方法进行处理,通过气相色谱 - 质谱碎片分析法和多离子检测法对两种衍生代谢产物(M - 1和M - 2)进行定量。分析结果表明,外源性标记的辅酶Q10的添加并未影响未标记的(内源性)辅酶Q10的代谢(或分解)。

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