Tryptophan metabolism and dispositions and utilisation in pregnancy

Synopsis 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 for signaling pathways; (3) kynurenic acid for neuronal protection; (4) quinolinic acid for NAD synthesis (5) other kynurenines 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 utilisation concept. Briefly, Trp is utilised as follows: (1) In early and midpregnancy, emphasis is on increased maternal Trp availability to meet the demand for protein synthesis and fetal development, most likely mediated by maternal liver Trp 2,3-dioxygenase inhibition by progesterone and oestrogens. (2) In midand late pregnancy, Trp availability is maintained and enhanced by the release of albumin-bound Trp by albumin depletion and nonesterified fatty acid (NEFA) elevation, leading to increased flux of Trp down the kynurenine pathway to elevate immunosuppressive kynurenines. An excessive release of free Trp could undermine pregnancy by abolishing T-cell suppression by kynurenines. Detailed assessment of parameters of Trp metabolism and disposition and related measures (free and total Trp, albumin, NEFA, kynurenine and its metabolites and proand 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. Ac ep t d M an us cr ip t