Studies on the oxidation of omega-hydroxyprostaglandins by an NAD-dependent dehydrogenase from mammalian liver cytosol.
Studies on the oxidation of omega-hydroxyprostaglandins by an NAD-dependent dehydrogenase from mammalian liver cytosol.
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研究哺乳动物肝细胞质中 NAD 依赖性脱氢酶对 omega-羟基前列腺素的氧化作用。
DOI：
10.1016/0003-9861(80)90276-3
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发表时间：
1980
影响因子：
3.9
通讯作者：
A. Theoharides
中科院分区：
文献类型：
--
作者：
D. Kupfer;J. Navarro;G. K. Miranda;D. E. Piccolo;A. Theoharides
在存在NAD的情况下，用大鼠、家兔和豚鼠的肝细胞溶质证明了12-羟基月桂酸甲酯（12-OH-L-Me）和ω-羟基-野牡丹素（ω-OH-PG）（如20-OH-PGB 1和20-OH-PGE 1）的氧化;然而，NADP不支持这种氧化。（ω-1）-羟基化合物（11-OH-月桂酸酯和19-OH-PGB 1）和PGE 1、PGF 1 α和PGB 1（均缺乏末端（ω）-羟基）不能降低NAD。然而，在pH 10时，PGE 1略微增强NAD还原，表明在此pH下PGE 1可为15-羟基-PG脱氢酶（PGDH）的底物。分离12-OH-L-Me、20-OH-PGB 1-Me和20-OH-PGE 1与豚鼠肝胞液孵育的氧化产物，并通过气相色谱/质谱法鉴定为相应的二羧酸。与肝胞液相反，豚鼠肾胞液对12-OH-L-Me还原NAD的影响很小，但支持PGE 1和PGF 1 α（但不支持PGB 1）刺激NAD还原，表明肾胞液PGDH参与PGE 1和PGF 1 α氧化，并证明ω-OH氧化为羧酸不是由PGDH介导的。虽然ω-OH-PGs的氧化过程尚不明确，但这些结果表明，尿中二羧基-PG代谢产物涉及PGs的多个连续步骤氧化，包括内质网中NADPH-细胞色素P-450系统的ω-羟基化和随后胞质中NAD依赖性脱氢酶对ω-OH的氧化。
The oxidation of 12-hydroxylauric acid methyl ester (12-OH-L-Me) and of ω-hydroxy-prostaglandins (ω-OH-PGs) such as 20-OH-PGB1and 20-OH-PGE1, was demonstrated with liver cytosol from rat, rabbit, and guinea pig in the presence of NAD; however, NADP did not support this oxidation. (ω-1)-Hydroxy-compounds (11-OH-laurate and 19-OH-PGB1) and PGE1, PGF1α, and PGB1, all lacking the terminal (ω)-hydroxyl, did not reduce NAD. However, at pH 10, PGE1slightly enhanced NAD reduction, suggesting that at this pH PGE1, could be a substrate for 15-hydroxy-PG dehydrogenase (PGDH). The oxidation products from incubations of 12-OH-L-Me, 20-OH-PGB1-Me, and 20-OH-PGE1with guinea pig liver cytosol were isolated and identified by gas chromatography/mass fragmentation spectrometry as being the corresponding dicarboxylic acids. In contrast to the liver cytosol, guinea pigkidneycytosol had only a minimal effect on NAD reduction by 12-OH-L-Me but nevertheless did support the stimulation of NAD reduction by PGE1, and PGF1α, but not by PGB1, indicating the participation of kidney cytosolic PGDH in PGE1and PGF1αoxidation and demonstrating that the oxidation of ω-OH to the carboxylic acid is not mediated by PGDH. Though thein vivorate of oxidation of ω-OH-PGs has not been established, these results suggest that the urinary dicarboxylic-PG metabolites involve a multiple sequentialstep oxidation of PGs involving ω-hydroxylation by an NADPH-cytochromeP-450 system in the endoplasmic reticulum and the subsequent oxidation of the ω-OH by an NAD-dependent dehydrogenase in the cytosol.