Species Differences in Tryptophan Metabolism and Disposition

Abstract

Major species differences in tryptophan (Trp) metabolism and disposition exist with important physiological, functional and toxicity implications. Unlike mammalian and other species in which plasma Trp exists largely bound to albumin, teleosts and other aquatic species possess little or no albumin, such that Trp entry into their tissues is not hampered, neither is that of environmental chemicals and toxins, hence the need for strict measures to safeguard their aquatic environments. In species sensitive to toxicity of excess Trp, hepatic Trp 2,3-dioxygenase (TDO) lacks the free apoenzyme and its glucocorticoid induction mechanism. These species, which are largely herbivorous, however, dispose of Trp more rapidly and their TDO is activated by smaller doses of Trp than Trp-tolerant species. In general, sensitive species may possess a higher indoleamine 2,3-dioxygenase (IDO) activity which equips them to resist immune insults up to a point. Of the enzymes of the kynurenine pathway beyond TDO and IDO, 2-amino-3-carboxymuconic acid-6-semialdehyde decarboxylase (ACMSD) determines the extent of progress of the pathway towards NAD⁺ synthesis and its activity varies across species, with the domestic cat (Felis catus) being the leading species possessing the highest activity, hence its inability to utilise Trp for NAD⁺ synthesis. The paucity of current knowledge of Trp metabolism and disposition in wild carnivores, invertebrates and many other animal species described here underscores the need for further studies of the physiology of these species and its interaction with Trp metabolism.

Keywords: Albumin; indoleamine 2,3-dioxygenase; kynurenine pathway; plasma tryptophan; serotonin; tryptophan 2,3-dioxygenase; tryptophan toxicity.

Figure 1.

The tryptophan degradative pathways. Abbreviations: Acet, acetaldehyde; ACMS, 2-Amino-3-carboxymuconic acid-6-semialdehyde: also known as acroleyl aminofumarate, AMS, 2-Aminomuconic acid -6-semialdehyde; AA, anthranilic acid; 3-HAA, 3-hydroxyanthranilic acid; 5-HIAcet, 5-hydroxyindoleacetaldehyde; 5-HIAA, 3-hydroxyindoleacetic acid; 3-HK, 3-hydroxykynurenine; 5-HT, 5-hydroxytryptamine or serotonin; 5-HTP, 5-hydroxytryptophan; IAcet, indole acetaldehyde; IAA, indol-3-ylacetic acid; ILA, indol-3-yllactic acid; IPA, indol-3-ylpyruvic acid; KA, kynurenic acid; PA, picolinic acid; QA, quinolinic acid; XA, xanthurenic acid. Bold numbers represent enzymes of the different pathways, as follows: 1 (tryptophan hydroxylase); 2 (aromatic L-amino acid decarboxylase); 3 monoamine oxidase); 4 (aldehyde dehydrogenase); 5 (alkyl amine N-acetyl transferase); 6 (hydroxyindole o-methyl transferase); 7 (tryptophan aminotransferase); 8 (indole lactate dehydrogenase); 9 (indole pyruvate decarboxylase); 10 (tryptophan 2,3-dioxygenase); 11 (indoleamine 2,3-dioxygenase); 12 (N′-formylkynurenine formamidase); 13 (kynureninase); 14 (kynurenine aminotransferase); 15 (kynurenine monooxygenase: also known as kynurenine hydroxylase); 16 (3-hydroxyanthranilic acid 34-dioxygenase); 17 (non-enzymic cyclisation); 18 (2-Amino-3-carboxymuconic acid-6-semialdehyde decarboxylase (ACMSD: also known as picolinate carboxylase).

Figure 2.

Correlations between plasma albumin and tryptophan concentrations and tryptophan binding in humans and other species. (A) Healthy human volunteers (n = 114) with mean albumin values of 49.6 g/l (range: 40.7-57.4). (B–E) correlations with 35 different animal species between albumin and the % free Trp (B), free Trp (C), total Trp (D) and bound Trp (E).

Figure 3.

Correlation between plasma albumin concentration and turnover rate. Pearson moment product correlations were made between plasma [albumin] and albumin T1/2 for the 9 animal species described in the text, the T1/2 of which rose in the following order: mouse < rabbit < cat = dog < pig < cow < horse < man < sheep.

Figure 4.

Ranking of ACMSD activity among species. Ranking was based on levels of enzyme activity similarly expressed in a single study by Ikeda et al.