5-Hydroxyindoleacetic acid excretion

An intermediate in the conversion of tryptophan to 5-hydroxy tryptamine (serotonin). In some cases of carcinoid syndrome it i excreted in large amounts in the urine, even though the 5 hydroxyindoleacetic acid excretion may be normal. This i thought to be because the cells lack the decarboxylase whicl converts 5-hydroxytryptophan to 5-hydroxytryptamine. 

Colorimetric assays used in endocrinological procedures are also often subject to drug interference. We have observed an interesting interference in a patient with carcinoid. The patient excreted 400 mg of 5-hydroxyindoleacetic acid (5-HIAA) and when a vanillylmandclic acid (VMA) determination was performed by a nonspecific diazo method, the value was reported to be 375 mg. The catecholamines were just above normal. There was an immediate suggestion that the patient also had a pheochromocytoma. However, when a specific chromatographic VMA method was used, the value was found to be within normal limits. Subse-... 

The enzymes responsible for the metabolism of serotonin are present in all of the cells containing this amine and in the Uver. Serotonin is initially oxidatively deami-nated to form 5-hydroxyindoleacetaldehyde this compound is subsequently rapidly oxidized to the major metabolite 5-hydroxyindoleacetic acid, which is excreted in the urine. Much of the serotonin released in the brain at synapses is taken back into the initial neuron by an active reuptake mechanism to be released again. 

Serotonin is metabolized by MAO, and the intermediate product, 5-hydroxyindoleacetaldehyde, is further oxidized by aldehyde dehydrogenase to 5-hydroxyindoleacetic acid (5-HIAA). In humans consuming a normal diet, the excretion of 5-HIAA is a measure of serotonin synthesis. Therefore, the 24-hour excretion of 5-HIAA can be used as a diagnostic test for tumors that synthesize excessive quantities of serotonin, especially carcinoid tumor. A few foods (eg, bananas) contain large amounts of serotonin or its precursors and must be prohibited during such diagnostic tests. 

Focusing our attention on the serotonin branch of Figure 20.21, it is seen that the initial hydroxylation reaction requires tetrahydrobiopterin, which was introduced in Chapter 16 and is discussed further here. Serotonin per se is a neurotransmitter, and it can give rise to melatonin in the pineal gland. Melatonin is synthesized at night, and is believed to be associated with the phenomenon of circadian rhythms. Serotonin is metabolized to 5-hydroxyindoleacetic acid, which is excreted in the urine. Normal 5-hydroxyindoleacetic add excretion is about 7 mg/day, whereas in carcinoid tumor patients, this may be as high as 400 mg/day. Carcinoid is an intestinal tumor that may metastasize into the liver. 

On account of the activity of these plant extracts and the isolation from them of iV,iV-dimethyltryptamine, the physiological activity of this base in humans is of interest. When injected intramuscularly, it causes hallucinations and illusions, which are characterized by their rapid appearance and brief duration (80). Apparently, dimethyltrypt-amine is rapidly metabolized and excreted mainly as indoleacetic acid, although the urine is enriched with 5-hydroxyindoleacetic acid whether this is the result of oxidation at the 5-position or stimulation of the metabolism of serotonin in the brain is not yet known (80). 

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. 

Finally, it was found (B7) that the excretion of 5-hydroxyindoleacetic acid, which is taken as an index of tryptophan metabolism by the serotonin pathway, is affected by the administration of tryptophan neither in normal nor in schizophrenic subjects. 

It has been observed (D6) Aat addition of vitamin Be to insulin therapy allowed the employment of lower doses of insuhn and, in one subject, the total cessation of insulin administration. Finally, Oka and Leppanen (04) studied the tryptophan metabolism in 10 patients with diabetes mellitus and in 12 control subjects by determining the urinary excretion of 5-hydroxyindoleacetic acid, kynurfenine, and anthranilic, 3-hydroxyanthranilic, and xanthurenic acids before and after a load of 2 g L-tryptophan. The authors noted a markedly increased excretion of... 

More recently, Olson et al. (05) reported that in 34 patients with chronic alcoholism the excretion of 5-hydroxyindoleacetic acid was significantly lower than in normal controls, after oral ingestion of 10 g DL-tryptophan. Such lowered excretion was unaffected by improved nutritional status or abstinence from ethyl alcohol. The urinary excr on of xanthurenic acid was similar in the alcoholic and control groups. The conclusions indicate that in chronic alcoholism the conversion of tryptophan to 5-hydroxyindoleacetic acid is preferentially depressed, while the kynurenine pathway is normal (05). 

Serotonin. Many fruits and vegetables that contain 5-hydroxytryptamine (serotonin), such as bananas, cause an increased excretion of 5-hydroxyindoleacetic acid. Avocados impair glucose tolerance by affectmg insulin secretion. Onions reduce both the plasma glucose and insulin response to glucose. 

Caffeine, Caffeine is contained in many beverages, including coffee, tea, and colas and has considerable effect on the concentration of blood constituents. Caffeine stimulates the adrenal medulla, causing an increased excretion of the catecholamines and their metabolites and a slight increase in the plasma glucose concentration with impairment of glucose tolerance. The adrenal cortex is also affected plasma cortisol is increased, accompanied by increased excretion of free cortisol, 11-hydroxycorticoids, and 5-hydroxyindoleacetic acid. The effect of caffeine may be so great that the normal diurnal variation of plasma cortisol may be suppressed. 

Smoking affects both the adrenal cortex and the medulla plasma 11-hydroxycorticosteroids may be increased by 75% with heavy smoking. In addition, the plasma cortisol concentration may increase by as much as 40% within 5 minutes of the start of smoking, although the normal diurnal rhyth-micity of cortisol is unaffected. Smokers excrete more 5-hydroxyindoleacetic acid than do nonsmokers. 

Feldman JM, Lee EM. Serotonin content of foods effect on urinary excretion of 5-hydroxyindoleacetic acid. Am J Clin Nutr 1985 42 639-43. 

A large amount of 5-hydroxyindoleacetic acid is excreted by patients with malignant carcinoid. 

Hernberg S, Nikkanen J, Mellin G, Lilius H (1970) J-Aminolevulinic acid dehydratase as a measure of lead exposure. Arch Environ Health 21 140-145 Ho JW (1990) Determination of porphyrins in human blood by high performance liquid chromatography. J Liquid Chromatog 13 2179-2192 Ichiba M, Tomokuni K (1987) Urinary excretion of 5-hydroxyindoleacetic acid, S-aminolevulinic acid and coproporphyrin isomers in rats and men exposed to lead. Toxicol Lett 38 91-96... 

Considerable information about serotonin metabolism has been learned from the action of monoamine oxidase inhibitors. One of the first of these compounds to be discovered was l-isonicotinyl-2-isopropyl hydrazide (Marsilid) 376) Many other compounds have since been discovered that inhibit monoamine oxidase both in vHxo and in vivo 368). The outcome of the studies with monoamine oxidase inhibitors has been to show that when the enzyme is inhibited there is a diminished formation of 5-hydroxyindoleacetic acid and serotonin is converted to the 0-glucuronide and excreted in rodents. In man there is little formation of serotonin glucuro-nide. The fate of serotonin in man under these conditions is not known definitely, although serotonin-O-sulfate has been observed in carcinoid patients. Serotonin may also be methylated to yield W-methyl-serotonin 368). 

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