Niacin serotonin

Tryptophan is also the precursor of niacin, serotonin, and melatonin. 

Pathways of metabolism have been outlined which indicate how tryptophan is a source of auxin, niacin, serotonin, ommochrome, and energy. Many other compounds are formed as side-products of these pathways and still others are formed by further reactions. Yet additional pathways remain to be elucidated to describe the formation of gramine (V-dimethyl-indole-3-methylamine), abrine (A -methyltryptophan), the a-hydroxy-tryptophan component of phalloidin, skatole, and possibly other complex compounds containing the indole nucleus. The reactions involved in these transformations include examples of various types of oxidation, transamination, cleavage, elimination, decarboxylation, and condensation as well as cis-trans isomerization. The wealth of biochemical variety already revealed in these studies is a stimulus toward exploration of the still unknown reactions of tryptophan metabolism. 

The role of cADP-ribose and NAADP in regulating cytosolic calcium may provide an alternative explanation to the serotonin hypothesis for the psychiatric and neurological signs of the niacin deficiency disease pellagra (Section 8.5 Petersen and Cancela, 1999). 

Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan and other large neutral amino acids. The result is that the intestinal absorption of free tryptophan is impaired, although dipeptide absorption is normal. There is a considerable urinary loss of tryptophan (and other amino acids) as a result of the failure of the normal reabsorption mechanism in the renal tubules - renal aminoaciduria. In addition to neurological signs that can be attributed to a deficit of tryptophan for the synthesis of serotonin in the central nervous system, the patients show clinical signs of pellagra, which respond to the administration of niacin. 

Nicotinate (also called niacin or vitamin Bg) is derived from tryptophan. Human beings can synthesize the required amount of nicotinate if the supply of tryptophan in the diet is adequate. However, nicotinate must be obtained directly if the dietary intake of tryptophan is low. A dietary deficiency of tryptophan and nicotinate can lead to pellagra, a disease characterized by dermatitis, diarrhea, and dementia. An endocrine tumor that consumes large amounts of tryptophan in synthesizing the hormone and neurotransmitter serotonin (5-hydroxytryptamine) can lead to pellagralike symptoms. 

In view of the hypoglycemic and insulinase-inhibitory action of l-tryptophan, it seemed pertinent to Mirsky to study the effect of various metabolic products of tryptophan on the blood sugar of normal and diabetic rats (M9), A statistically significant hypoglycemic response was produced after oral administration of anthranilic acid, niacin, indole-3-acetic acid, 5-hydroxytryptophan, and serotonin. A hypoglycemic fol-... 

Serotonin and melatonin are derived from tryptophan, as is the nicotinamide portion of NAD+ (which is also derived from the vitamin niacin). 

A precursor to the neurotransmitter serotonin, which promotes relaxation and sleep, tryptophan reduces anxiety and helps some forms of depression. It converts to niacin, lowers cholesterol, helps migraine headaches, and stimulates growth hormone. 

One of the substances commonly treated as a vitamin is niacin, which is synthesized from the essential amino acid tryptophan. The ratio is approximately 60 mg of tryptophan being required to produce 1 mg of niacin (1). This has led to niacin requirements being expressed as niacin equivalents (NE), based on the amount of tryptophan in the diet. It must be kept in mind that tryptophan is essential and is the precursor to the neurotransmitter serotonin in addition to being part of protein structure. Therefore, niacin can be thought of as tryptophan sparing. 

Pellagra-like symptoms can occur in Hartnup s disease and carcinoid syndrome. Hartnup s disease is an inherited disorder of amino acid transport (Chapter 17) in which niacin deficiency presumably develops because niacin intake is inadequate to supply metabolic needs when combined with the decreased absorption of dietary tryptophan. In carcinoid syndrome, up to 60% of available dietary tryptophan is diverted to formation of 5-hydroxytryptamine (serotonin) by what is normally a minor pathway. 

This chapter discusses the pathways by which L-tryptophan is metabolized into a variety of metabolites, many of which have important physiological functions. A few metabolites are cited here briefly. Quinolinic acid is involved in the regulation of gluconeogenesis. Picolinic acid is involved in normal intestinal absorption of zinc. The body s pool of nicotinamide adenine dinucleotide (NAD) is influenced by L-tryptophan s metabolic conversion to niacin. Finally, L-tryptophan is the precursor of several neuroactive compounds, the most important of which is serotonin (5-HT), which participates as a neurochemical substrate for a variety of normal behavioral and neuroendocrine functions. Serotonin derived from L-tryptophan allows it to become involved in behavioral effects, reflecting altered central nervous system function under conditions that alter tryptophan nutrition and metabolism. 

Niacin plays a number of essential roles in the body. It is necessary for cell respiration metabolism of proteins, fats, and carbohydrates the release of energy from foods the secretion of digestive enzymes the synthesis of sex hormones and the proper functioning of the nervous system. It is also involved in the production of serotonin, an essential... 

The Tryptophan-Niacin Pathway, the Serotonin Pathway, and Vitamin Bi. 264... 

Tryptophan is an essential amino acid which is ingested by Americans in quantities that exceed the normal daily requirements for protein synthesis (Rl), and considerable amounts are converted to nonprotein substances such as nicotinic acid and serotonin (Fig. 1). The tryptophan-niacin pathway, which is also known as the kynurenine pathway (Fig. 1), is important for production of the vitamin, nicotinic acid, and provides also a means for degrading tryptophan to acetoacetyl-CoA, carbon dioxide, and ammonia (P7). The amount of tryptophan metabolized by the various pathways available depends greatly on the amount of... 

Fic. 1. Metabolism of tryptophan to serotonin (5-hydroxytryptamine) and niacin. Fyiidoxal phosphate (PLP) dependent reactions are indicated. Reactions not shown which may result in formation of products excreted in urine include the acetylation of liymuenine and 3-hydroxykynurenine, conjugation of anthranilic acid with glycine (to form o-aminohippuric acid) and with glucuronic acid, and the dehydroxylation of kynurenic acid and xanthurenic add to quinaldic add and 8-hydroxyquinaldic add, respectively. 

L-Tryptophan is one of the essential amino acids in animals. In addition, it is the biosynthetic precursor to other important molecules such as serotonin (thus, melatonin) and niacin. Until 1989, L-Tryptophan was sold singly over-the-counter and as a constituent in dietary supplement combinations. One of several effects that ingesting L-tryptophan has on the body is an increase in serotonin levels. Partly because of this, L-tryptophan supplements commonly were used to treat premenstrual syndrome, as a sleep aid and as a natural antidepressant [8] (http //www. webmd.com/vitamins-supplements/ingredientmono-326-L-TRYPTOPHAN.aspx activebigredientId=326 activeIngredientName=L-TRYPTOPHAN source=3). 

Although pellagra is uncommon, it most frequently afflicts alcoholics and the elderly. Thyrotoxicosis and sepsis increase niacin requirements but rarely precipitate pellagra. Though the disease is produced by dietary insufficiency of tryptophan and niacin, the full deficiency syndrome can develop in patients who shunt tryptophan into other metabolic pathways despite a normal diet. Such is the case for patients with the carcinoid syndrome, in whom 60 times more tryptophan than normal is hydroxy-lated to serotonin (Melmon, 1981). 

Hartnup disease, an autosomal recessive trait that interferes with the absorption of tryptophan, and carcinoid syndrome in which the amino acid is preferentially oxidized to 5-hydroxytryptophan and serotonin. Prolonged treatment with the drug isoniazid, which competes with pyridoxal 5 -phosphate (a vitamin Be-derived coenzyme required in the tryptophan-to-niacin pathway), also reduces the conversion of tryptophan to niacin. Oral contraceptives that contain high doses of estrogen increase tryptophan conversion efficiency (Braidman and Rose 1971). 

There are numerous sources of niacin that are essential and these include poultry, fish (tuna, salmon), meat (beef), yeast, legumes, milk and fortified eereals. In addition, niacin is naturally occurring in tiny amounts and the human body can make nicotinic acid from the metabolism of dietary tryptophan (Vosper 2009). The body requires tryptophan for two main reasons (i) for the synthesis of niacin and (ii) to raise serotonin levels, which is essential for the regulation of sleep, appetite and mood. The vast majority of proteins contain about 1 % of tryptophan and it is suggested that approximately 100 g of protein intake a day will be sufficient to ensure optimum levels of niacin in the body. The recommended dose of niacin is higher when there is an increase in physiological states such as pregnancy and lactation. Importantly, the Committee of Medical Aspects of Food Policy (COMA) in the UK stated that the Reference Nutrient Intake (RNI) for niacin was 17 mg/day and 13 mg/day. 

The depressive psychosis is superficially similar to schizophrenia and the organic psychoses, but clinically distinguishable by the sudden lucid phases that alternate with the most florid psychiatric signs. It is probable that these mental symptoms can be explained by a relative deficit of the essential amino acid tryptophan, and hence reduced synthesis of the neurotransmitter serotonin, and not to a deficiency of niacin per se. 

Other claims for megadoses of nicotinic acid or nicotinamide, such as the claim that abnormalities associated with schizophrenia, Down s syndrome, hyperactivity in children, etc. can be reduced, have so far failed to win general acceptance. Clearly niacin deficiency or dependency can exacerbate some types of mental illness such as depression or dementia. There have been a number of attempts to treat depression with tryptophan or niacin, or both, on the basis that the correction of depressed brain levels of serotonin would be advantageous. However, these have met with only limited success. Schizophrenics have been treated with nicotinic acid on the basis that their synthesis of NAD is impaired in some parts of the brain, and that the formation of hallucinogenic substances such as methylated indoles may be controlled. 

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