Tryptophan metabolism

The kynurenine pathway accounts for most of the nonprotein tryptophan metabolism in most tissues. Several metabolites produced by this pathway have been shown... 

Pewnim T, Seifert J. 1993. Structural requirements for altering the L-tryptophan metabolism in mice by organophosphorous and methylcarbamate insecticides. Eur J Pharmacol 248 237-241. 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Kaderbhai, N. N. Broadhurst, D. I. Ellis, D. I. Goodacre, R. Kell, D. B. Functional genomics via metabolic footprinting monitoring metabolite secretion by Escherichia coli tryptophan metabolism mutants using FT-IR and direct injection electrospray mass spectrometry. Compar. Func. Genomics 2003, 4, 376-391. 

B19. Banerjee, S., and Agarival, P. S., Nicotinic acid-tryptophan metabolism in certain diseases. Proc. Soc. Exptl. Biol. Med. 97, 65-68 (1958). 

Valine, leucine, and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine, and tryptophan biosynthesis Urea cycle and metabolism of amino groups... 

The Lac operon is but one example of the genetic adaptations which allow bacteria to respond to their environment. Other examples are to be found in amino acid metabolism, for example the TRP operon which regulates tryptophan metabolism. 

Bender J Celenza JL (2009) Indolic glucosinolates at the crossroads of tryptophan metabolism. Phytochem Rev 8 25-37... 

Aspects of Disorders of the Kynurenine Pathway of Tryptophan Metabolism in Man... 

The end products of tryptophan metabolism in the stick insect, Carausius morosus, are the ommochromes ommin and xanthommatin (58) in the epidermis, and kynurenic acid (53) in the feces. During larval development of this insect kynurenic acid (53) is the major end product of tryptophan metabolism (Table V) (109,110). Additionally, this insect contains five pteridines (Table VI), of which leucopterin (68), xanthopterin (65), and isoxanthopterin (67) are the origin of the yellow-white color of the insect (111). 

Y. Umebachi, in Biochemical and Medical Aspects of Tryptophan Metabolism (O. Hay-aishi, Y. Ishimura, R. Kido, eds.), p. 117. Elsevier, Amsterdam, 1980. 

Seifert J, Pewnim T. 1992. Alteration of mice L-tryptophan metabolism by the organophosphorous acid triester diazinon. Biochem Pharmacol 44(11) 2243-2250. 

Botting NP (1995) Chemistry and biochemistry of the kynurenine pathway of tryptophan metabolism. Chem Soc Rev 24, 401-412. 

Sugimura, T. Kawachi, M. Nagao, M. Yamada, M. Takayama, S. Matsukawa, N. Wakabayashi, K. "Biochemical and Medical Aspects of Tryptophan Metabolism", Elsevier/North Holland, 1980, p. 297-310. 

In addition to altering the activities of enzymes from the MFO system in the liver, 2,3,7,8-TCDD also alters the activities of some key liver enzymes of the intermediary metabolism. These effects are intimately related with the wasting syndrome as discussed below (see Body Weight Effects). For example, 2,3,7,8-TCDD decreased the activities of hepatic PEPCK and G-6-Pase (key enzymes of gluconeogenesis) in mice and rats (Fan and Rozman 1995 Li and Rozman 1995 Viluksela et al. 1994 Weber et al. 1995) and also reduced the activity of TdO (key enzyme of tryptophan metabolism) in rats (Li and Rozman 1995 Viluksela et al. 1994), but not in mice (Weber et al. 1995). 

Unkila M, Pohjanvirta R, MacDonald E, et al. 1994. Dose response and time course of alterations in tryptophan metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the most TCDD-susceptible and the most TCDD-resistant rat strain Relationship with TCDD lethality. Toxicol Appl Pharmacol 128 280-292. 

Urine Progressive form of albuminuria from the nonprogressive form of albuminuria Type 1 diabetic patients normoalbuminuric56. After 5.5 years micro/macroalbuminuric 26 normoalbuminuric 26 GC-MS LC-MS Acylcarnitines, acyl-glycines, and metabolites related to the tryptophan metabolism (56)... 

Khodursky AB, Peter BJ, Cozzarelli NR et al (2000) DNA microarray analysis of gene expression in response to physiological and genetic changes that affect tryptophan metabolism in Escherichia coli. Proc Natl Acad Sci USA 97 12170-12175... 

Tryptophan metabolism does not produce any propionyl-CoA precursors, such as a-ketobutyrate. The other four amino acids do. 

Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH. Interferon-alfa-induced changes in tryptophan metabolism. Relationship to depression and paroxetine treatment. Biol Psychiatry 2003 54 906-14. 

The disturbance of tryptophan metabolism in riboflavin deficiency, caused by impairment of kynurenine hydroxylase, can also result in reduced synthesis of NAD from tryptophan. This may therefore be a factor in the etiology of pellagra (Section 8.3.3.1). 

It is not strictly correct to regard niacin as a vitamin. Its metabolic role is as the precursor of the nicotinamide moiety of the nicotinamide nucleotide coenzymes, nicotinamide adenine dinucleotide (NAD) and NADP, and this can also be synthesized in vivo from the essential amino acid tryptophan. At least in developed countries, average intakes of protein provide more than enough tryptophan to meet requirements for NAD synthesis without any need for preformed niacin. It is only when tryptophan metabolism is disturbed, or intake of the amino acid is inadequate, that niacin becomes a dietary essential. 

As shown in Figure 8.2, NAD(P) can be synthesized from the tryptophan metaboUte quinolinic acid. The oxidative pathway of tryptophan metabolism is shown in Figure 8.4. Under normal conditions, almost aU of the dietary intake of tryptophan, apart from the small amount that is used for net new protein synthesis, is metabolized by this pathway, and hence is potentially available for NAD synthesis. About 1% of tryptophan metabolism is by way of 5-hydroxylation and decarboxylation to 5-hydroxytryptarnine (serotonin), which is excreted mainly as 5-hydroxyindoleacetic acid. 

---