Short-term supplementation of isocaloric meals with L-tryptophan affects pig growth.

L-Tryptophan (Trp) and some of its metabolites regulate the circadian rhythm in mammals. We aimed to investigate the effects of short-term supplementation of Trp in isocaloric meals on growth performance using the parameters of multiple blood biomarkers and free amino acids in growing pigs. A total of 32 Landrace × Yorkshire barrows with a mean body weight of 8.64 (±1.13) kg were randomly assigned to four groups and then fed with various concentrations of Trp diets daily. Our results showed that sequential supplementation of different concentrations of Trp in isocaloric meals decreased the feed:gain (F:G) ratio (P = 0.079) and plasma urea and albumin (P = 0.019), whereas the level of total protein did not. Among the essential and conditionally essential amino acids, the concentrations of histidine, isoleucine, proline, threonine, arginine, and valine in the plasma decreased (P < 0.05), whereas the concentrations of Trp, glycine, serine, and methionine increased (P < 0.01). In addition, concentrations of branched chain amino acids also significantly decreased (P = 0.004), while the rate of conversion of Trp to branched chain amino acids increased (P < 0.001). Taken together, we show that administration of a high concentration of Trp in breakfast with decreasing concentrations of Trp in lunch and dinner positively affected feed utilization and improved feed efficiency, at least in part, through the optimization of amino acid interconversions and nitrogen utilization.

Human Delta1-pyrroline-5-carboxylate synthase: function and regulation.

Mammalian Delta(1)-pyrroline-5-carboxylate synthase (P5CS) is a bifunctional ATP- and NAD(P)H-dependent mitochondrial enzyme that catalyzes the coupled phosphorylation and reduction-conversion of L: -glutamate to P5C, a pivotal step in the biosynthesis of L: -proline, L: -ornithine and L: -arginine. Previously, we reported cloning and characterization of two P5CS transcript variants generated by exon sliding that encode two protein isoforms differing only by a two amino acid-insert at the N-terminus of the gamma-glutamyl kinase active site. The short form (P5CS.short) is highly expressed in the gut and is inhibited by ornithine. In contrast, the long form (P5CS.long) is expressed ubiquitously and is insensitive to ornithine. Interestingly, we found that all the established human cell lines we have studied expressed P5CS.long but not P5CS.short. In addition, expression of P5CS.long can be modulated by hormones: downregulation by hydrocortisone and dexamethasone and upregulation by estradiol, for example. Using a quantitative proteomic approach, we showed that P5CS.long is upregulated by p53 in p53-induced apoptosis in DLD-1 colorectal cancer cells. Functional genomic analysis confirmed that there are two p53-binding consensus sequences in the promoter region and in the intron 1 of the human P5CS gene. Interestingly, overexpression of P5CS by adenoviruses harboring P5CS.long or P5CS.short in various cell types has no effect on cell growth or survival. It would be of importance to further investigate the role of P5CS as a p53 downstream effector and how P5CS.short expression is regulated by hormones and factors of alternative splicing in cells isolated from model animals.