The tryptophan utilization concept in pregnancy

Abstract

The decrease in maternal plasma total (free + albumin-bound) tryptophan (Trp) during the third pregnancy trimester is attributed to induction of indoleamine 2,3-dioxygenase (IDO). When measured, free [Trp] is increased because of albumin depletion and non-esterified fatty acid elevation. The Trp depletion concept in pregnancy is therefore not supported because of incorrect interpretation of changes in Trp disposition and also for not addressing mouse strain differences in Trp-related responses and potential inhibition of Trp transport by the IDO inhibitor 1-methyl tryptophan. Application of the Trp utilization concept in pregnancy offers several physiological advantages favoring fetal development and successful outcome, namely provision of Trp for fetal protein synthesis and growth, serotonin for signaling pathways, kynurenic acid for neuroprotection, quinolinic acid for NAD+ synthesis, and other kynurenines for suppression of T cell responses. An excessive increase in Trp availability could compromise pregnancy by undermining T cell suppression, e.g., in pre-eclampsia.

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

“…These results are in line with previous research [26][27][28]. The physiopathological mechanism of decreasing TRP during infection and inflammation is a matter of current discussion [29]. It has been hypothesized early on that diseaseassociated starvation and depletion by microbes may cause these effects.…”

Tryptophan pathway alterations in the postpartum period and in acute postpartum psychosis and depression

“…A few studies have suggested that the occurrence of postpartum mood symptoms could be related to increased tryptophan breakdown (Figure 1), a physiological phenomenon of pregnancy and the postpartum period (Kohl et al, 2005;Maes et al, 2002). During pregnancy, tryptophan metabolism is altered, with a decrease in total tryptophan and a shift in the proportions of free and bound tryptophan (Badaway, 2014). After pregnancy, both free and bound tryptophan levels gradually return to pre-pregnancy levels (Handley et al, 1977;Schrocksnadel et al, 1996;Schrocksnadel et al, 2003).…”

Negative effects on newborn piglets caused by excess dietary tryptophan in the morning in sows

“…Some deleterious effects of elevated KYNA levels during gestation have been reported. The maternal plasma KYNA level is elevated in preeclampsia, and elevated plasma KYNA level during pregnancy was suggested to be strongly associated with increased risk of preeclampsia in women, which is usually accompanied by complications including placental abruption, organ damage, fetal growth restriction and others . Animal studies revealed KYNA was a potent inhibitor of the synthesis of fatty acids in rat liver .…”

“…The maternal plasma KYNA level is elevated in preeclampsia, and elevated plasma KYNA level during pregnancy was suggested to be strongly associated with increased risk of preeclampsia in women, which is usually accompanied by complications including placental abruption, organ damage, fetal growth restriction and others. 43,44 Animal studies revealed KYNA was a potent inhibitor of the synthesis of fatty acids in rat liver. 45,46 Elevated levels of KYNA during gestation induced neurochemical, morphological and cognitive deficits in offspring in adulthood, modeling the pathophysiological deficits during the sensitive periods of early development.…”