Ellis C K, Smigel M D, Oates J A, Oelz O, Sweetman B J
J Biol Chem. 1979 May 25;254(10):4152-63.
[3H7]Prostaglandin D2 was biosynthesized and infused into an unanesthetized monkey. The urinary metabolites were isolated and subsequently identified by gas chromatography-mass spectrometry. Two pathways of prostaglandin D2 metabolism were identified and resulted in metabolites with prostaglandin D (3-hydroxycyclopentanone) and prostaglandin F (cyclopentane-1,3-diol) ring structures. The major prostaglandin D ring metabolite was identified as 9,20-dihydroxy-11,15-dioxo-2,3-dinorprost-5-en-1-oic acid. Nine other prostaglandin D ring metabolites were identified reflecting various combinations of metabolism by beta and omega oxidation, 15 dehydrogenation, and 13-14 reduction. In greater abundance were those prostaglandin D2 metabolites which had the prostaglandin F ring structure. The major prostaglandin D2 metabolite which had the prostaglandin F ring structure was identified as 9,11,15-trihydroxy-2,3-dinorprosta-5,13-dien-1-oic acid (dinor prostaglandin F2 alpha). Nine other metabolites with the prostaglandin F ring structure were identified, including prostaglandin F2 alpha itself. These, for the most part, were the structural counterparts of the metabolites with the prostaglandin D ring. Since many prostaglandin D2 metabolites were found to be identical with the metabolites of prostaglandin F2 alpha, quantitative determinations of prostaglandin F ring metabolites may not be a specific indicator of prostaglandin F2 alpha biosynthesis. Likewise, data involving the measurement of a biological effect of prostaglandin D2 must be re-examined to account for the possible contribution of prostaglandin F2 alpha, a metabolite of prostaglandin D2, to the biological response.
[3H7]前列腺素D2经生物合成后注入未麻醉的猴子体内。分离出尿液代谢产物,随后通过气相色谱-质谱联用仪进行鉴定。确定了前列腺素D2的两条代谢途径,其代谢产物具有前列腺素D(3-羟基环戊酮)和前列腺素F(环戊烷-1,3-二醇)环结构。主要的前列腺素D环代谢产物被鉴定为9,20-二羟基-11,15-二氧代-2,3-二去甲前列腺-5-烯-1-酸。还鉴定出了其他九种前列腺素D环代谢产物,反映了β氧化和ω氧化、15位脱氢以及13-14位还原的各种代谢组合。具有前列腺素F环结构的前列腺素D2代谢产物含量更为丰富。具有前列腺素F环结构的主要前列腺素D2代谢产物被鉴定为9,11,15-三羟基-2,3-二去甲前列腺-5,13-二烯-1-酸(二去甲前列腺素F2α)。还鉴定出了其他九种具有前列腺素F环结构的代谢产物,包括前列腺素F2α本身。这些产物在很大程度上是具有前列腺素D环的代谢产物的结构对应物。由于发现许多前列腺素D2代谢产物与前列腺素F2α的代谢产物相同,因此对前列腺素F环代谢产物的定量测定可能不是前列腺素F2α生物合成的特异性指标。同样,涉及测量前列腺素D2生物学效应的数据必须重新审视,以考虑前列腺素D2的代谢产物前列腺素F2α对生物反应可能产生的影响。