CONVERSION OF D‐ AND L‐TRYPTOPHAN TO BRAIN SEROTONIN AND 5‐HYDROXYINDOLEACETIC ACID AND TO BLOOD SEROTONIN 1

Abstract— Intraperitoneal administration of both D‐ or L‐tryptophan elevated the levels of serotonin and 5‐hydroxyindoleacetic acid in the brains of hypophysectomized and intact rats. In intact rats, the increase in brain 5‐hydroxyindoles was slower after D‐tryptophan than after L‐tryptophan. Similarly, brain tryptophan rose more slowly after administration of D‐tryptophan. The uptake of L‐tryptophan from blood into brain was at a rate about one‐third that of 3H2O. D‐tryptophan uptake was at 1/25 that of 3H2O. Brain and liver tryptophan aminotransferase activities were stereospecific for the L‐isomer and no evidence could be found for a tryptophan racemase in brain. Evisceration prevented the increase in brain 5‐hydroxyindoles following peripheral administration of D‐tryptophan administration but not that after L‐tryptophan. The serotonin ratios between the two brain regions examined remained constant following administration of either D‐ or L‐tryptophan. On the basis of these results we concluded that the increase in brain 5‐hydroxyindoles following administration of L‐tryptophan was not dependent upon stress‐induced changes in pituitary hormones and that the elevations after D‐tryptophan were dependent upon its prior conversion to L‐tryptophan via peripheral deamination and subsequent transamination.

[1]  W H Oldendorf,et al.  Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. , 1971, The American journal of physiology.

[2]  R. Wurtman,et al.  Brain Serotonin Content: Physiological Dependence on Plasma Tryptophan Levels , 1971, Science.

[3]  L. Wetterberg,et al.  RELATIONSHIP BETWEEN ALTERNATE ROUTES OF TRYPTOPHAN METABOLISM FOLLOWING ADMINISTRATION OF TRYPTOPHAN PEROXIDASE INDUCERS OR STRESSORS 1 , 1971, Journal of neurochemistry.

[4]  L. Wetterberg,et al.  Alterations in induction of tyrosine aminotransferase and tryptophan oxygenase by glucose pretreatment. , 1970, Biochimica et biophysica acta.

[5]  Y. Nishizuka,et al.  Enzymic studies on the biosynthesis of serotonin in mammalian brain. , 1970, The Journal of biological chemistry.

[6]  M. Roberts,et al.  Long Term Effects of Midbrain Stimulation on 5-Hydroxyindole Synthesis in Rat Brain , 1970, Nature.

[7]  E. Ritvo,et al.  A rapid accurate procedure for the determination of serotonin in whole human blood. , 1970, Biochemical medicine.

[8]  E. Azmitia,et al.  Corticosterone Regulation of Tryptophan Hydroxylase in Midbrain of the Rat , 1969, Science.

[9]  M. Jouvet,et al.  Biogenic amines and the states of sleep. , 1969, Science.

[10]  J. Glowinski,et al.  Effects of stress on the metabolism of noradrenaline, dopamine and serotonin (5HT) in the central nervous system of the rat. (II). Modifications of serotonin metabolism. , 1968, European journal of pharmacology.

[11]  D. Eccleston,et al.  THE EFFECTS OF PRECURSOR LOADING IN THE CEREBRAL METABOLISM OF 5‐HYDROXYINDOLES , 1968, Journal of neurochemistry.

[12]  D. Sarma,et al.  Effect of dietary tryptophan on hepatic polyribosomes and protein synthesis in fasted mice. , 1968, The Journal of biological chemistry.

[13]  C. McKean,et al.  THE INFLUENCE OF HIGH PHENYLALANINE AND TYROSINE ON THE CONCENTRATIONS OF ESSENTIAL AMINO ACIDS IN BRAIN , 1968, Journal of neurochemistry.

[14]  L. Valzelli,et al.  A method for the determination of 5‐hydroxyindolyl‐3‐acetic acid in brain , 1966, Journal of neurochemistry.

[15]  D. B. Goldstein d‐AMINO ACID OXTDASE IN BRAIN: DISTRIBUTION IN SEVERAL SPECIES AND INHIBITION BY PENTOBARBITONE , 1966, Journal of neurochemistry.

[16]  P. Ray,et al.  Paths of carbon in gluconeogenesis and lipogenesis. IV. Inhibition by L-tryptophan of hepatic gluconeogenesis at the level of phosphoenolpyruvate formation. , 1966, The Journal of biological chemistry.

[17]  B. Ginsberg,et al.  THE NATURE OF IN VITRO HYDROXYLATION OF l‐TRYPTOPHAN BY BRAIN TISSUE , 1966, Journal of neurochemistry.

[18]  A. Neims,et al.  DISTRIBUTION OF d‐AMINO ACID OXIDASE IN BOVINE AND HUMAN NERVOUS TISSUES * , 1966, Journal of neurochemistry.

[19]  S H Snyder,et al.  A sensitive and specific fluorescence assay for tissue serotonin. , 1965, Biochemical pharmacology.

[20]  F. Fonnum,et al.  TRANSAMINATION OF AROMATIC AMINO ACIDS IN RAT BRAIN , 1964, Journal of neurochemistry.

[21]  J. Barchas,et al.  BRAIN AMINES: RESPONSE TO PHYSIOLOGICAL STRESS. , 1963, Biochemical pharmacology.

[22]  W. Knox The adaptive control of tryptophan and tyrosine metabolism in animals. , 1963, Transactions of the New York Academy of Sciences.

[23]  E. Lin,et al.  The assay of aromatic amino acid transaminations and keto acid oxidation by the enol borate-tautomerase method. , 1958, The Journal of biological chemistry.

[24]  H. Weissbach,et al.  Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan. , 1957, The Journal of biological chemistry.

[25]  R. Schayer Studies of the metabolism of tryptophan labeled with N15 in the indole ring. , 1950, The Journal of biological chemistry.

[26]  H. Jasper,et al.  Physiological salt solutions for brain surgery; studies of local pH and pial vessel reactions to buffered and unbuffered isotonic solutions. , 1949, Journal of neurosurgery.

[27]  H. Krebs Metabolism of amino-acids: Deamination of amino-acids. , 1935, The Biochemical journal.

[28]  W. Lovenberg,et al.  Tryptophan hydroxylation in mammalian systems. , 1968, Advances in pharmacology.

[29]  N. J. Giarman,et al.  Serotonin, norepinephrine, and fever. , 1968, Advances in pharmacology.

[30]  L. Valzelli,et al.  Studies on behavioural and biochemical changes in rats after lesion of midbrain raphé. , 1968, European journal of pharmacology.

[31]  C. Wise An improved and simplified method for the fluorometric determination of brain serotonin , 1967 .

[32]  H. Dewey,et al.  The determination of tryptophan in plasma, liver, and urine. , 1967, The Journal of laboratory and clinical medicine.

[33]  V. E. Davis Effect of cortisone and thyroxine on aromatic amino acid decarboxylation. , 1963, Endocrinology.

[34]  A. Yuwiler,et al.  Studies on 5-hydroxytryptophan decarboxylase. I. In vitro inhibition and substrate interaction☆ , 1959 .

[35]  O. Wiss,et al.  Zur Kenntnis des Abbaues der Aminosäuren im tierischen Organismus. 3. Über den oxydativen Abbau der Aminosäuren im Gehirn , 1944 .

[36]  C. P. Berg,et al.  Tryptophane metabolism. 2. The growthpromoting ability of dl-tryptophane. , 1932 .