Tryptophan manufacture

After initial studies implicated the consumption of tryptophan as a major risk factor for EMS, US state and federal health agencies began investigations to further examine this association. Consumers of tryptophan were classified as either case (EMS patients) or control (non-EMS tryptophan users), and the lots of tryptophan consumed by each group were traced back to determine the tryptophan source. Before the epidemic, L-tryptophan had been manufactured by six companies, all in Japan. Analysis of the tryptophan sources for case patients and controls demonstrated a strong association between EMS and consumption of tryptophan manufactured by a single company, Showa Denko K. K. (Tokyo), a large petrochemical company. 

Figure 2 Typicai HPLC chromatograms of i-tryptophan manufactured by the six different companies. (Reproduced from Mayeno AN and Gieich GJ (1994) Eosinophiiia - myaigia syndrome and tryptophan production. A cautionary taie. Trends in Biotechnoiogy 12 346-352, with permission from Eisevier.)...

Because of the simplicity of swiae and poultry feeds, most feed manufacturers add vitamins (qv) and trace minerals to ensure an adequate supply of essential nutrients. Amino acids (qv) such as methionine [7005-18-7] lysiae [56-87-17, threonine [36676-50-3] and tryptophan [6912-86-3], produced by chemical synthesis or by fermentation (qv), are used to fortify swiae and poultry diets. The use of these supplements to provide the essential amino acids permits diets with lower total cmde proteia coateat. 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

Still, some members of the lay public are clearly skeptical of science and scientists, as indicated by the view of the profession presented on the cover of a national magazine in Figure 6.110 Although we may be assured that scientists as a group are no more deficient in morals than, say, cartoonists, it is important to understand the basis of public perceptions and to examine the practical implications for laboratory management. Industrial products are very widely distributed and many are used intimately. There are real consequences that can arise from a serious error in manufacture or design, as illustrated by the case of L-tryptophan. 

L-tryptophan is a naturally-produced, natural amino acid used as a dietary supplement. Samples from one manufacturer were found to be contaminated by trace amounts of another naturally occurring compound — l,l -ethylidene bis-[i.-tryptophan]. The latter compound appears to have been responsible for causing a number of deaths and additional cases of chronic eosinophilia-myalgia,111 some of which might have been prevented had there... 

What kind of business This depends largely on what kind of dope you plan to manufacture. Amine-type precursors go hand in hand with perfumery or dyes. Nitrating-type compounds (nitromethane, nitroethane) are also used as solvents, and rocket fuels. Indole has been used in perfumery. Tyrosine and tryptophan are nutrients added to feeds. Urea is a plant fertilizer and a feed additive. 

In 1989, the amino acid dietary supplement L-tryptophan was thought to he associated with an outbreak of eosinophila-myalgia syndrome (EMS), a condition characterized by an increase in white blood cell count, severe muscle pain, and other skin and neuromuscular problems. Later studies showed that an impurity present during the manufacture of the amino acid was probably responsible for the outbreak of EMS and that the amino acid itself was probably safe for human consumption. 

Vitamins must be derived from the diet because either they cannot be synthesized de novo in human beings or their rate of synthesis, e.g. the production of nicotinic acid from tryptophan, is inadequate for the maintenance of health. Only vitamin D can be manufactured by the body at a sufficient rate. 

Neurons manufacture serotonin in a series of chemical reactions, beginning with the amino acid tryptophan. Catalyzing these reactions are specific enzymes, such as an enzyme known as tryptophan hydroxylase, which speeds up a reaction that adds a hydroxyl group (an OH molecule) to tryptophan. Serotonin is packaged into vesicles, with each vesicle... 

The reliability and consistency of commercial melatonin has been questioned (3). One group analysed three commercial melatonin formulations and identified analogues of the contaminant of L-tryptophan compounds implicated in an epidemic of eosinophilia-myalgia syndrome in the 1980s (27). There have been no reports of this condition associated with melatonin consumption, but food supplements are not required to comply with the same manufacturing and monitoring quality control standards as drugs. 

There are 22 different AAs in the body of the bird, 10 of which are essential AA (EAA arginine, methionine, histidine, phenylalanine, isoleucine, leucine, lysine, threonine, tryptophan and valine), i.e. cannot be manufactured by the body and must be derived from the diet. Cystine and tyrosine are semi-essential in that they can be synthesized from methionine and phenyla-... 

Near infra red reflectance spectroscopy (NIRS) is becoming increasingly used for the analysis of nutrients in feedstuffs. It is very rapid and cost-effective and may eventually replace the slower chemical methods of analysis used currently in the feed-manufacturing industry. NIRS may also be used for amino acid analysis. Another method now being adopted widely in feed manufacture is to use predichon equations based on chemical or NIRS analysis to predict amino acid contents of some feedstuffs. The NRC (1994) published equations for the predichon of lysine, tryptophan, threonine,... 

Another case, much more serious and also more pertinent to the chemical process development area, occurred in 1989 when over 1600 people became ill with eosinophilia-myalgia syndrome (EMS) and 38 died, worldwide, after taking l-tryptophan (Trp) manufactured by one producer in Japan. Prior to the outbreak, this producer whose Trp met the >98.5% purity specification had decided to employ a new genetically modified strain of the established Bacillus amyloliquefaciens and also to halve the amount of activated charcoal used in the purification step. These changes cause the Trp product to become contaminated with several new impurities, principally I to III, all associated to some extent (using a crude animal model) with EMS.5... 

Amino Acids. Amino acids are produced by both fermentation and biocatalysis for use in animal feed, fertilizer, as flavor enhancers, dietary supplements, and in pharmaceutical manufacture. By volume, the most important products are L-lysine, L-methionine, L-threonine, and L-tryptophan, most of which are produced by fermentation. Biocatalysis still plays an important role in amino acid supply and has been used to synthesize both L- and D-amino acids, including a variety of nonnatural analogues. The major producers are Degussa, Tanabe Seiyaku, and Kyowa Hakko. 

The amino acid L-tryptophan (19), used as a food supplement and in insomnia, is manufactured in Japan by a novel biotechnological process that leads to the contaminant bisindole 50 (peak E) 126), for which earlier an aminal structure was proposed 127). An outbreak of an eosinophilia... 

Although all of the amino acids listed in Table SO-1 are present in the proteins of the human body, not all of them need to be in the food. Experiments have been carried out which show that nine of the amino acids are essential to man. 1 hese nine essential amino acids are histidine, lysine, tryptophan, phenylalanine, leucine, isoleucine, threonine, methionine, and valine. The human body seems to be able to manufacture the others, which are called the non-essential amino acids. Some organisms that we usually consider to be simpler than man have greater powers than the human organism, in that they are able to manufacture all of the amino acids from inorganic constituents. The red bread mold, Neurospora, has this power. 

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