{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T20:26:08Z","timestamp":1763497568870},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,11]],"date-time":"2004-10-11T00:00:00Z","timestamp":1097452800000},"content-version":"vor","delay-in-days":5581,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[1989,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The daytime administration of the heme precursor 5\u2010aminolevulinate (5\u2010ALA) has been shown to reduce brain tryptophan and serotonin levels owing to saturation of liver tryptophan pyrrolase. Saturation of this enzyme with heme results in enhanced activity, leading to increased catabolism of tryptophan and thus making less tryptophan available to the brain. Tryptophan is also the precursor of melatonin, a primary secretory product of the pineal gland. Reduced melatonin levels, which could be a consequence of altered tryptophan metabolism, have been associated with depressive disorders in humans. In view of this, in the present study we examined the effects of 5\u2010ALA administration on forebrain tryptophan and serotonin levels as well as pineal serotonin, melatonin, and the pineal melatonin\u2010forming enzymes N\u2010acetyltransferase (NAT) and hydroxyindole\u2010O\u2010methyltransferase (HIOMT). 5\u2010ALA induced a reduction in forebrain tryptophan and serotonin levels during the light phase and caused the opposite effect in the dark phase. Allopurinol, an inhibitor of hepatic tryptophan pyrrolase activity, prevented the reduction in the indole levels induced by 5\u2010ALA. Although 5\u2010ALA induced these changes in the forebrain, it did not alter either daytime or nighttime pineal NAT, HIMOT, serotonin, or melatonin levels. It appears that high serotonin levels and melatonin production in the pineal are conserved even in the face of low circulating tryptophan levels, changes which alter brain tryptophan and serotonin concentrations.<\/jats:p>","DOI":"10.1002\/jnr.490230309","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T01:44:22Z","timestamp":1104543862000},"page":"304-309","source":"Crossref","is-referenced-by-count":19,"title":["Heme precursor 5\u2010aminolevulinic acid alters brain tryptophan and serotonin levels without changing pineal serotonin and melatonin concentrations"],"prefix":"10.1002","volume":"23","author":[{"given":"S.","family":"Daya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. O.","family":"Nonaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. R.","family":"Buzzell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. J.","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,11]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S0021-9258(18)64458-8","article-title":"Purification and properties of hydroxyindole\u2010O\u2010methyltransferase","volume":"236","author":"Axelrod J","year":"1961","journal-title":"J Biol Chem"},{"key":"e_1_2_1_3_1","first-page":"7","article-title":"Central role tryptophan pyrrolase in heme metabolism","volume":"7","author":"Badaway AAB","year":"1979","journal-title":"Biochem Soc Trans"},{"key":"e_1_2_1_4_1","first-page":"136","article-title":"The effects of chemical porphyrogens and drugs on the activity of liver tryptophan pyrrolase","volume":"136","author":"Badaway AAB","year":"1973","journal-title":"Biochem J"},{"key":"e_1_2_1_5_1","first-page":"133","article-title":"The mechanism of inhibition of rat liver tryptophan pyrrolase activity by allopurinol","volume":"133","author":"Badaway AAB","year":"1973","journal-title":"Biochem J"},{"key":"e_1_2_1_6_1","first-page":"150","article-title":"The regulation of rat liver tryptophan pyrrolase by its cofactor","volume":"150","author":"Badaway AAB","year":"1975","journal-title":"Biochem J"},{"key":"e_1_2_1_7_1","first-page":"198","article-title":"Tryptophan pyrrolase in heme regulation","volume":"198","author":"Badaway AAB","year":"1981","journal-title":"Biochem J"},{"key":"e_1_2_1_8_1","first-page":"248","article-title":"Effects of the heme 5\u2010aminolevulinate on tryptophan metabolism and disposition in the rat","volume":"248","author":"Badaway AAB","year":"1987","journal-title":"Biochem J"},{"key":"e_1_2_1_9_1","first-page":"303","article-title":"Dependence of 5\u2010HT and catecholamine synthesis on concentrations of precursor amino acids in rat brain","volume":"303","author":"Carlsson A","year":"1978","journal-title":"Naunyn Schmledebergs Arch Pharmacol"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490110107"},{"key":"e_1_2_1_11_1","first-page":"231","volume-title":"Advances in Pineal Research","author":"Dietzel M","year":"1987"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1042\/bj1291095","article-title":"The effect of exogenous 5\u2010aminolevulinate on rat liver heme and cytochromes","volume":"129","author":"Druyan R","year":"1972","journal-title":"Biochem J"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.173.3992.149"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(59)90105-4"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.12.3107"},{"key":"e_1_2_1_16_1","first-page":"5","article-title":"Circadian variation in the uptake of tryptophan by cortical synaptosomes of the rat brain","volume":"5","author":"Loizon G","year":"1988","journal-title":"Chronobiologia"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)81604-7"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001620402"},{"key":"e_1_2_1_19_1","first-page":"96","volume-title":"The Brain as an Endocrine Organ","author":"Reiter RJ","year":"1988"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-98-2-482"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)90115-5"},{"key":"e_1_2_1_22_1","first-page":"141","volume-title":"Pineal Research Reviews","author":"Vaughan GM","year":"1984"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(69)90156-8"},{"key":"e_1_2_1_24_1","first-page":"2","article-title":"Melatonin and cortisol levels in psychiatric illness","volume":"2","author":"Wetterberg L","year":"1982","journal-title":"Lancet"},{"key":"e_1_2_1_25_1","first-page":"151","volume-title":"Biostatistical Analysis","author":"Zar JH","year":"1974"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.490230309","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.490230309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T06:56:19Z","timestamp":1697957779000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.490230309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,7]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1989,7]]}},"alternative-id":["10.1002\/jnr.490230309"],"URL":"https:\/\/doi.org\/10.1002\/jnr.490230309","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,7]]}}}