Tryptophan in poultry nutrition-Mohammad Behroozlak

Tryptophan Supervisor: Prof. Farhoomand

Presenter: M. Behroozlak Urmia University

Departement of Animal ScienceJun 2014

Intoduction

• Tryptophan amino acid is the essential amino acid. This means it must be provided through food to the body. It is one of the amino acid which in its molecule contains an indole ring.

• Tryptophan is glucogenic as well as ketogenic amino acid. It has codon UGG. It has two stereoisomers, namely L-tryptophan and D-tryptophan.

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Intoduction

• L-tryptophan can only be utilized in the structure or enzymes proteins while D–tryptophan is normally present in naturally occurring peptides. Tryptophan has aromatic side chain and is relatively polar.

• The N of the indole ring present in tryptophan gives polarity to this amino acid.

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Intoduction

• Tryptophan is an essential constituent of the diet. It plays an important role in protein synthesis, and is also the precursor of a variety of biologically active compounds including serotonin, melatonin, tryptamine, quinolinic acid and kynurenic acid.

• In addition, tryptophan is a precursor to the

coenzymes NAD and NADP, and can replace niacin as an essential nutrient.

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Isolation

• While other amino acids were isolated from acid digests of proteins, the isolation of tryptophan was first reported by Frederick Hopkins in 1901 through hydrolysis of casein.

• From 600 grams of crude casein one obtains 4-8 grams of tryptophan.

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Biosynthesis and industrial production

• Plants and microorganisms commonly synthesize tryptophan from shikimic acid or anthranilate. The latter condenses with phosphoribosylpyrophosphate (PRPP), generating pyrophosphate as a by-product.

• After ring opening of the ribose moiety and following reductive decarboxylation, indole-3-glycerinephosphate is produced, which in turn is transformed into indole.

• In the last step, tryptophan synthase catalyzes the formation of tryptophan from indole and the amino acid serine.

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• The industrial production of tryptophan is also biosynthetic and is based on the fermentation of serine and indole using either wild type or genetically modified bacteria such as B. amyloliquefaciens, B. subtilis or E. coli.

• The conversion is catalyzed by the enzyme tryptophan synthase.

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Functions & metabolic processes of tryptophan

• In humans, tryptophan has relatively low tissue storage and the overall tryptophan concentration in the body is the lowest among all amino acids, although only small amounts are necessary for general healthy nutrition.

• While typical intake for many individuals is approximately 900 to 1000 mg daily, the recommended daily allowance for adults is estimated to be between 250 mg/day and 425 mg/day.

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Protein synthesis

• The principal role of tryptophan in the human body is as a constituent of protein synthesis. Because tryptophan is found in the lowest concentrations among the amino acids, it is relatively less available and is thought to play a rate-limiting role during protein synthesis.

• Tryptophan is also the precursor of two important metabolic pathways, kynurenine synthesis and serotonin synthesis.

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Kynurenine synthesis

• After protein synthesis, the second most prevalent metabolic pathway of tryptophan is for the synthesis of kynurenine, which accounts for approximately 90% of tryptophan catabolism.

• Kynurenine is a key component in the synthesis of a number of metabolites, but most importantly, it is the precursor of kynurenic and quinolinic acids.

• kynurenine is known to be involved in acting as an ultra violet (UV) filter which protects the retina of the eye from UV damage. The effectiveness of this protection deteriorates with age. 12

Kynurenine synthesis

• N-formylkynurenine and kynurenine are the first metabolites of a complex metabolic pathway ending in quinolinic acid, niacin, kynurenic and xanthurenic acid.

• Two enzymes are able to catalyze the conversion of tryptophan into N-formylkynurenine: tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO).

• These two enzymes differ in their tissue localization, structure, substrate specificity, cofactor requirement and function. Whereas IDO is widespread in numerous tissues, TDO is mainly located in the liver. 13

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Serotonin synthesis

• It is estimated that 95% of mammalian serotonin is found within the gastrointestinal tract, and only 3% of dietary tryptophan is used for serotonin synthesis throughout the body.

• It is estimated that only 1% of dietary tryptophan is used for serotonin synthesis in the brain, but despite the relatively low concentration of brain serotonin compared to that in the rest of the body, it has a broad impact as a neurotransmitter and neuromodulator and has been implicated in numerous psychiatric conditions and psychological processes. 15

Serotonin synthesis

• Tryptophan is the precursor of serotonin (5-HT or 5-hydroxytryptamine), an important neuromediator regulating gastrointestinal functions, mood, appetite.

• Serotonin seems to act as a trophic factor in the developing brain and is also a neurotransmitter. Serotonin has a modulatory role in neural information processing. It is thought to inhibit a variety of behaviors including aggression, impulsivity, selection of food and arousal, sexual behavior and reaction to pain. In addition, serotonin is involved in the control of mood.

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Tryptamine synthesis

• Tryptamine is another biologically active compound that is derived from tryptophan. The immediate decarboxylation of tryptophan results in the synthesis of trace amounts of tryptamine, which is an important neuromodulator of serotonin.

• Numerous animal studies have indicated that tryptamine acts as a control for the balance between excitatory and inhibitory functions of serotonin, and in other instances, tryptamine acts as a neurotransmitter with specific receptors that are independent of serotonin function.

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Melatonin synthesis

• Melatonin is a hormone produced in the tryptophan/ serotonin pathway, which regulates diurnal rhythms and influences the reproductive and immune systems, as well as digestive processes and gastrointestinal motility.

• During periods of darkness, it is actively secreted from the pineal gland to induce neural and endocrine effects that regulate circadian rhythms of behavior, physiology, and sleep patterns.

• Synthesis of melatonin is inhibited by light.

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NAD/NADP synthesis

• Tryptophan also plays a role as a substrate for synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP).

• NAD and NADP are coenzymes essential for electron transfer reactions (i.e. redox reactions) in all living cells.

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These coenzymes can be synthesized de novo from ingested tryptophan, or from ingestion of niacin (i.e. vitamin B3).

Niacin synthesis

• Interestingly, tryptophan can act as a substrate for niacin synthesis through the kynurenine/ quinolinic acid pathway.

• However, this is a less efficient use of tryptophan since approximately 60 mg of tryptophan are necessary to generate a single milligram of niacin.

• Thus, an intake of 900mg of tryptophan should result in the synthesis of about 15mg niacin, while a daily intake of 11 to 13mg niacin is adequate to prevent depletion of body stores of niacin.

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Physiological metabolism of tryptophan

• Unlike other amino acids, tryptophan circulates in blood and plasma mainly (90%) bound to albumin. Only 10–20% of tryptophan is present as free form in the plasma.

• Tryptophan is transported into the brain by a transporter located in capillaries of the blood–brain barrier (BBB).

• In the bloodstream, tryptophan competes with other large neutral amino acids (LNAA).

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• The LNAA comprise leucine, valine, isoleucine, the three branched chain amino acids (BCAA), tyrosine, phenylalanine and methionine.

• Consequently, tryptophan entry into the brain is

influenced by the ratio between tryptophan and amino acids sharing the same transporter and, particularly, BCAA, which are present in higher proportion than tryptophan in plasma.

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• To some extent, tryptophan availability to the brain can be enhanced by ingestion of carbohydrates and reduced by ingestion of proteins.

• Carbohydrate ingestion does not change the levels of circulating tryptophan, but it does decrease concentrations of LNAA through activation of insulin, which increases the relative availability of tryptophan for transport into the brain.

• In contrast, protein contains relatively low concentrations of tryptophan and ingestion of a protein meal increases the LNAA concentration relative to tryptophan. 24

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Tryptophan: a key nutrient in the regulation of feed intake

• It has been clearly demonstrated in piglets that an adequate dietary Trp:Lys ratio, enhances feed intake.

• The effect of tryptophan on appetite regulation could be mediated through the regulation of the central production of serotonin which is involved in the regulation of satiation and appetite.

• Melatonin which is produced from tryptophan in the gastrointestinal tract, may serve as a signal for the synchronization of the feeding and digestion processes.

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• The effect of tryptophan on the regulation of appetite could also be explained by its effect on the gene expression and the synthesis of the ghrelin hormone. Ghrelin is an appetite stimulating hormone produced and secreted by the stomach and the duodenum.

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Dietary tryptophan content improving ghrelin gene expression, it increases feed intake and weight gain.


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Biological roles of tryptophan

• Tryptophan is usually the fourth limiting amino acid after lysine, threonine and the sulphur amino acids (methionine + cysteine).

• As lysine and threonine, tryptophan is an indispensable amino acid for body protein deposition and growth. Thus, deficiency in tryptophan affects the utilization of dietary lysine and threonine and consequently animal growth.

• Besides its utilization for protein synthesis, tryptophan is involved in other biological functions such as appetite regulation, immune response and health maintenance 30

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Sources of tryptophan

• Tryptophan is found in foods of animal origin as well foods of plant origin in abundant amount. Some of the foods in which it is present are as follow:

• Animal Origin: Chicken, turkey, fish, egg, milk, cheese, beef etc.

• Plant origin: Nuts, peanuts, peanut butter, pumpkin seed, soy, sunflower seed, rice, banana, potato and wheat flower etc.

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