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乳清酸喂养诱导的脂肪肝中类固醇的代谢

The metabolism of steroids in the fatty liver induced by orotic acid feeding.

作者信息

Carrella M, Björkhem I, Gustafsson J A, Einarsson K, Hellström K

出版信息

Biochem J. 1976 Jul 15;158(1):89-95. doi: 10.1042/bj1580089.

Abstract
  1. The metabolism of 4-[4-14C]androstene-3,17-dione, 4-[4-14C]pregnene-3,20-dione, 5alpha-[4-14C]androstane-3alpha,17beta-diol, [4-14C]cholesterol, 7alpha-hydroxy-4-[6beta-3H]cholesten-3-one, 5beta-[7beta-3H]cholestane-3alpha,7alpha-diol and [3H]lithocholic acid was studied in the microsomal fraction of livers from control and orotic acid-treated male rats. 2. As a result of the treatment the orotic acid-fed rats had fatty livers and subnormal concentrations of cholesterol and triglycerides in serum. 3. The 6beta- and 7alpha-hydroxylation of 4-androstene3,17-dione, and the 2alpha-, 2beta- and 18-hydroxylation of 5alpha-androstane-3alpha,17beta-diol, and the 5alpha-reduction of 4-androstene-3,17-dione and 4-pregnene-3,20-dione were decreased by 40--50% in orotic acid-fed rats. Other oxidative and reductive reactions of the steroid hormones were not significantly affected. 4. The 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one was decreased by about 50%, whereas the 7alpha-hydroxylation of cholesterol and the 26-hydroxylation of 5beta-cholestane-3alpha,7alpha-diol were not significantly decreased. The 6beta-hydroxylation of lithocholic acid was stimulated by 40%. 5. The results are discussed in relation to present knowledge of the heapatic drug-metabolizing enzymes and to the recent findings of an abnormal bile acid metabolism in liver disease.
摘要
  1. 研究了4-[4-¹⁴C]雄甾烯-3,17-二酮、4-[4-¹⁴C]孕烯-3,20-二酮、5α-[4-¹⁴C]雄甾烷-3α,17β-二醇、[4-¹⁴C]胆固醇、7α-羟基-4-[6β-³H]胆甾烯-3-酮、5β-[7β-³H]胆甾烷-3α,7α-二醇和[³H]石胆酸在对照和乳清酸处理的雄性大鼠肝脏微粒体部分的代谢。2. 作为处理的结果,喂食乳清酸的大鼠出现脂肪肝,血清中胆固醇和甘油三酯浓度低于正常水平。3. 在喂食乳清酸的大鼠中,4-雄甾烯-3,17-二酮的6β-和7α-羟基化、5α-雄甾烷-3α,17β-二醇的2α-、2β-和18-羟基化以及4-雄甾烯-3,17-二酮和4-孕烯-3,20-二酮的5α-还原减少了40%-50%。甾体激素的其他氧化和还原反应未受到显著影响。4. 7α-羟基-4-胆甾烯-3-酮的12α-羟基化减少了约50%,而胆固醇的7α-羟基化和5β-胆甾烷-3α,7α-二醇的26-羟基化未显著减少。石胆酸的6β-羟基化增加了40%。5. 结合目前关于肝脏药物代谢酶的知识以及肝病中胆汁酸代谢异常的最新发现对结果进行了讨论。

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本文引用的文献

5
Fatty liver induced by orotic acid feeding.由乳清酸喂养诱导的脂肪肝。
Proc Soc Exp Biol Med. 1955 Oct;90(1):270-1. doi: 10.3181/00379727-90-22005.
9
Effect of dietary orotic acid and adenine sulfate on hepatic microsomal enzymes in male and female rats.
Biochem Pharmacol. 1969 Aug;18(8):1922-33. doi: 10.1016/0006-2952(69)90288-3.

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