Tryptophan metabolism, disposition and utilization in pregnancy.
Tryptophan metabolism, disposition and utilization in pregnancy.
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DOI：
10.1042/bsr20150197
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发表时间：
2015-09-17
影响因子：
4
通讯作者：
Badawy AA
中科院分区：
文献类型：
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作者：
Badawy AA
必需氨基酸色氨酸（Trp）在妊娠期间对母体和胎儿的蛋白质合成、胎儿的生长发育以及通过免疫抑制预防胎儿排斥反应尤为重要。基于这些生理需求，提出了妊娠期Trp利用概念。妊娠期对色氨酸（Trp）的需求是多方面的：(1)母亲和胎儿生长发育需要增加蛋白质合成；(2) 5-羟色胺（5-HT）参与信号通路；(3)犬尿酸（KA），具有神经元保护作用；(4)喹啉酸（QA）用于合成NAD+(5)其他犬尿氨酸（Ks）用于抑制胎儿排斥反应。如果母体血浆[Trp]耗尽，这些目标就无法实现。妊娠期血浆总色氨酸（游离+白蛋白结合）降低，游离色氨酸升高。上述要求最好用Trp利用概念来表达。简而言之，色氨酸的用途如下：(1)在妊娠早期和中期，重点是增加母体色氨酸的可用性，以满足蛋白质合成和胎儿发育的需要，这很可能是通过孕激素和雌激素抑制母体肝脏色氨酸2,3-双加氧酶（TDO）介导的。(2)在妊娠中后期，白蛋白耗竭和非酯化脂肪酸（NEFA）升高使白蛋白结合的色氨酸释放，从而维持和增强色氨酸的可用性，导致色氨酸在K通路上的通量增加，从而升高免疫抑制性Ks。游离Trp的过量释放可能通过消除Ks对t细胞的抑制而破坏妊娠。对正常妊娠和异常妊娠中色氨酸代谢和处置参数的详细评估以及相关测量（母体血液中游离和总色氨酸、白蛋白、NEFA、K及其代谢物、促炎性和抗炎性细胞因子，以及适当的胎盘和胎儿物质）可能会弥补我们对妊娠期色氨酸状态知识的缺失，并有助于确定适当的干预策略。
The essential amino acid tryptophan (Trp) is especially important in pregnancy for protein synthesis by mother and fetus, fetal growth and development and prevention of fetal rejection by immunosuppression. A Trp utilization concept based on these physiological requirements in pregnancy is proposed. Tryptophan (Trp) requirements in pregnancy are several-fold: (1) the need for increased protein synthesis by mother and for fetal growth and development; (2) serotonin (5-HT) for signalling pathways; (3) kynurenic acid (KA) for neuronal protection; (4) quinolinic acid (QA) for NAD+ synthesis (5) other kynurenines (Ks) for suppressing fetal rejection. These goals could not be achieved if maternal plasma [Trp] is depleted. Although plasma total (free + albumin-bound) Trp is decreased in pregnancy, free Trp is elevated. The above requirements are best expressed in terms of a Trp utilization concept. Briefly, Trp is utilized as follows: (1) In early and mid-pregnancy, emphasis is on increased maternal Trp availability to meet the demand for protein synthesis and fetal development, most probably mediated by maternal liver Trp 2,3-dioxygenase (TDO) inhibition by progesterone and oestrogens. (2) In mid- and late pregnancy, Trp availability is maintained and enhanced by the release of albumin-bound Trp by albumin depletion and non-esterified fatty acid (NEFA) elevation, leading to increased flux of Trp down the K pathway to elevate immunosuppressive Ks. An excessive release of free Trp could undermine pregnancy by abolishing T-cell suppression by Ks. Detailed assessment of parameters of Trp metabolism and disposition and related measures (free and total Trp, albumin, NEFA, K and its metabolites and pro- and anti-inflammatory cytokines in maternal blood and, where appropriate, placental and fetal material) in normal and abnormal pregnancies may establish missing gaps in our knowledge of the Trp status in pregnancy and help identify appropriate intervention strategies.
DOI：
10.4137/ijtr.s5169
发表时间：
2010
期刊：
International journal of tryptophan research : IJTR
影响因子：
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作者：
Badawy AA;Dougherty DM;Richard DM
通讯作者：
Richard DM