title: Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin.
abstract: Serotonin (5-hydroxytryptamine [5-HT]) has been implicated in a variety of physiological and pathological functions. Multiple steps of enzyme reactions enable biosynthesis of 5-HT. The first and rate-limiting step of the reaction is the synthesis of 5-hydroxy-L-tryptophan (5-HTP) from L-tryptophan. This step is dictated by an enzyme, tryptophan hydroxylase (TPH). TPH requires 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as a co-substrate of TPH. 5-HTP has been simply regarded as a precursor of 5-HT and it is believed that the biological significance of 5-HTP is essentially ascribed to the production of 5-HT. However, recent works shed light on the specific functions of 5-HTP in the periphery. In this review article, we focus on the specific roles of exogenous 5-HTP as well as the endogenous 5-HTP in the gut epithelial cells. Since systemic treatment with 5-HTP is applied to patients with lower 5-HT levels, the studies on the specific role of 5-HTP might create an opportunity to explore the effects of exogenously-applied 5-HTP in the gut in man.
authors.affiliation: Department of Pathology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hasegawa
references.citation: Life Sci. 1974 Nov 1;15(9):1533-48
references.pmid: 4620982
references.citation: Arch Biochem Biophys. 1970 Aug;139(2):361-9
references.pmid: 5501632
references.citation: Neurology. 2001 Sep 11;57(5):908-11
references.pmid: 11552030
references.citation: Science. 2006 Apr 7;312(5770):104-7
references.pmid: 16601191
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 May;282(5):G877-93
references.pmid: 11960784
references.citation: Mol Genet Metab. 2005 Dec;86 Suppl 1:S145-7
references.pmid: 16165384
references.citation: J Biol Chem. 1964 Sep;239:2910-7
references.pmid: 14216443
references.citation: J Inherit Metab Dis. 2000 Jun;23(4):313-6
references.pmid: 10896282
references.citation: Mol Neurobiol. 2007 Feb;35(1):45-54
references.pmid: 17519505
references.citation: Eur J Biochem. 1999 May;261(3):734-9
references.pmid: 10215890
references.citation: Neurosci Lett. 1987 Oct 5;80(3):263-7
references.pmid: 3317138
references.citation: Curr Drug Metab. 2002 Apr;3(2):123-31
references.pmid: 12003346
references.citation: Science. 1996 Nov 29;274(5292):1527-31
references.pmid: 8929413
references.citation: J Pharmacol Sci. 2004 Oct;96(2):124-33
references.pmid: 15467264
references.citation: Biochem J. 1967 Oct;105(1):351-60
references.pmid: 6056632
references.citation: Eur J Biochem. 2002 Oct;269(19):4780-8
references.pmid: 12354109
references.citation: J Biol Chem. 1958 Feb;230(2):931-9
references.pmid: 13525410
references.citation: Curr Drug Metab. 2002 Apr;3(2):159-73
references.pmid: 12003348
references.citation: J Neurochem. 1980 Apr;34(4):933-40
references.pmid: 6444665
references.citation: Biochem J. 2000 Apr 1;347 Pt 1:1-16
references.pmid: 10727395
references.citation: J Immunol. 2004 May 15;172(10):6011-9
references.pmid: 15128784
references.citation: J Biol Chem. 1970 Apr 10;245(7):1699-709
references.pmid: 5309585
references.citation: Clin Sci (Lond). 2007 Jul;113(2):47-63
references.pmid: 17555404
references.citation: J Inherit Metab Dis. 2009 Feb;32(1):79-85
references.pmid: 19031009
references.citation: Mol Genet Metab. 2005 Dec;86 Suppl 1:S2-10
references.pmid: 16256391
references.citation: Cell. 2003 Dec 26;115(7):851-62
references.pmid: 14697203
references.citation: Biochim Biophys Acta. 1965 Nov 15;111(1):67-78
references.pmid: 5295589
references.citation: Brain Res. 1972 Dec 12;47(2):469-76
references.pmid: 4642573
references.citation: J Inherit Metab Dis. 2009 Feb;32(1):73-8
references.pmid: 18979179
references.citation: Mol Genet Metab. 2005 Dec;86 Suppl 1:S133-8
references.pmid: 16165391
references.citation: Brain Behav Immun. 1998 Dec;12(4):249-71
references.pmid: 10080856
references.citation: J Biol Chem. 1989 Dec 5;264(34):20496-501
references.pmid: 2584226
references.citation: Biol Psychiatry. 1998 Aug 1;44(3):151-62
references.pmid: 9693387
references.citation: Am J Pathol. 2008 Feb;172(2):333-44
references.pmid: 18202184
references.citation: Br J Pharmacol. 2003 May;139(2):457-63
references.pmid: 12770951
references.citation: Blood. 2006 Feb 1;107(3):1010-7
references.pmid: 16223770
references.citation: Mol Genet Metab. 2008 Aug;94(4):410-6
references.pmid: 18511317
references.citation: Brain Res. 1987 Nov 17;426(1):191-6
references.pmid: 3121135
references.citation: J Biol Chem. 1964 Dec;239:4081-90
references.pmid: 14247652
references.citation: J Biochem. 2000 Jan;127(1):121-7
references.pmid: 10731674
references.citation: Brain Res. 2008 Jun 27;1217:232-8
references.pmid: 18502400
references.citation: Digestion. 1999 Jan-Feb;60(1):63-8
references.pmid: 9892800
references.citation: Brain Behav Immun. 2004 Jan;18(1):24-34
references.pmid: 14651944
references.citation: Histochemistry. 1994 Jan;101(1):21-6
references.pmid: 8026979
references.citation: Science. 1967 Jan 13;155(3759):217-9
references.pmid: 6015530
references.citation: Annu Rev Biochem. 1985;54:729-64
references.pmid: 2862841
references.citation: Annu Rev Pharmacol Toxicol. 2003;43:261-84
references.pmid: 12359863
references.citation: Biochem Biophys Res Commun. 2005 Dec 9;338(1):277-84
references.pmid: 16185653
references.citation: J Comp Neurol. 1999 Sep 6;411(4):654-65
references.pmid: 10421874
references.citation: Clin Gastroenterol Hepatol. 2006 Jul;4(7):874-81
references.pmid: 16797248
references.citation: Cell Immunol. 1995 Jun;163(1):1-9
references.pmid: 7758118
references.citation: FEBS Lett. 1991 Aug 19;288(1-2):187-91
references.pmid: 1715290
references.citation: J Nutr. 2007 Jun;137(6 Suppl 1):1568S-1572S; discussion 1573S-1575S
references.pmid: 17513427
references.citation: J Leukoc Biol. 2001 Jul;70(1):65-72
references.pmid: 11435487