Histidine decarboxylase

Histidine decarboxylase
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4E1O​
Identifiers
Symbols	HDC ; MGC163399
External IDs	OMIM: 142704 MGI: 96062 HomoloGene: 20490 IUPHAR: 1274 GeneCards: HDC Gene
EC number	4.1.1.22
Gene ontology Molecular function • histidine decarboxylase activity • protein binding • pyridoxal phosphate binding Cellular component • cytosol Biological process • histamine biosynthetic process • histidine metabolic process • histidine catabolic process • cellular nitrogen compound metabolic process • catecholamine biosynthetic process • small molecule metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3067	15186
Ensembl	ENSG00000140287	ENSMUSG00000027360
UniProt	P19113	P23738
RefSeq (mRNA)	NM_001306146	NM_008230
RefSeq (protein)	NP_001293075	NP_032256
Location (UCSC)	Chr 15: 50.24 – 50.27 Mb	Chr 2: 126.59 – 126.62 Mb
PubMed search

histidine decarboxylase
Identifiers
EC number	4.1.1.22
CAS number	9024-61-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Histidine carboxylase PI chain
structure of the d53,54n mutant of histidine decarboxylase at-170 c
Identifiers
Symbol	HDC
Pfam	PF02329
InterPro	IPR003427
SCOP	1pya
SUPERFAMILY	1pya
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Histidine decarboxylase (HDC) is the enzyme that catalyzes the reaction that produces histamine from histidine with the help of vitamin B₆ as follows:^[1][2][3]

Conversion of histidine to histamine by histidine decarboxylase

In humans, the histidine decarboxylase enzyme is encoded by the HDC gene.^[4][5]

Function

The biogenic amine histamine is an important modulator of numerous physiologic processes, including neurotransmission, gastric acid secretion, and smooth muscle tone. The biosynthesis of histamine from histidine is catalyzed by the enzyme L-histidine decarboxylase. This homodimeric enzyme is a pyridoxal phosphate (PLP)-dependent decarboxylase and is highly specific for its histidine substrate.^[4]

Biosynthesis

In bacteria, it is synthesised as a proenzyme, PI. Cleavage of the proenzyme PI chain yields two subunits, alpha and beta, which arrange as a hexamer, (alpha beta)6, by nonhydrolytic self-catalysis.^[6]

Clinical significance

Inhibitors of histidine decarboxylase can be used as atypical antihistamines. (See Tritoqualine)

Mutations in the gene for this enzyme have been observed in one family with Tourette syndrome (TS) and are not thought to account for most cases of TS.^[7]

See also

• Aromatic L-amino acid decarboxylase

References

1. Epps HM (1945). "Studies on bacterial amino-acid decarboxylases: 4. l(-)-histidine decarboxylase from Cl. welchii Type A". Biochem. J. 39 (1): 42–6. PMC 1258146. PMID 16747851.
2. Riley WD, Snell EE (October 1968). "Histidine decarboxylase of Lactobacillus 30a. IV. The presence of covalently bound pyruvate as the prosthetic group". Biochemistry 7 (10): 3520–8. doi:10.1021/bi00850a029. PMID 5681461.
3. Rosenthaler J, Guirard BM, Chang GW, Snell EE (July 1965). "Purification and properties of histidine decarboxylase from Lactobacillus 30a". Proc. Natl. Acad. Sci. U.S.A. 54 (1): 152–8. doi:10.1073/pnas.54.1.152. PMC 285813. PMID 5216347.
4. "Entrez Gene: histidine decarboxylase".
5. Bruneau G, Nguyen VC, Gros F, Bernheim A, Thibault J (November 1992). "Preparation of a rat brain histidine decarboxylase (HDC) cDNA probe by PCR and assignment of the human HDC gene to chromosome 15". Hum. Genet. 90 (3): 235–8. doi:10.1007/bf00220068. PMID 1487235.
6. Coton E, Rollan GC, Lonvaud-Funel A (1998). "Histidine carboxylase of Leuconostoc oenos 9204: purification, kinetic properties, cloning and nucleotide sequence of the hdc gene.". J Appl Microbiol 84 (2): 143–51. doi:10.1046/j.1365-2672.1998.00271.x. PMID 9633629.
7. "Online Mendelian Inheritance in Man: histidine decarboxylase".

Further reading

• Need AC, Keefe RS, Ge D, et al. (2009). "Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.". Eur. J. Hum. Genet. 17 (7): 946–57. doi:10.1038/ejhg.2008.264. PMC 2986499. PMID 19156168.
• Masini E, Fabbroni V, Giannini L, et al. (2005). "Histamine and histidine decarboxylase up-regulation in colorectal cancer: correlation with tumor stage.". Inflamm. Res. 54 Suppl 1: S80–1. doi:10.1007/s00011-004-0437-3. PMID 15928846.
• Li Z, Liu J, Tang F, et al. (2008). "Expression of non-mast cell histidine decarboxylase in tumor-associated microvessels in human esophageal squamous cell carcinomas.". APMIS 116 (12): 1034–42. doi:10.1111/j.1600-0463.2008.01048.x. PMID 19133005.
• Szafranski K, Schindler S, Taudien S, et al. (2007). "Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns.". Genome Biol. 8 (8): R154. doi:10.1186/gb-2007-8-8-r154. PMC 2374985. PMID 17672918.
• Ai W, Liu Y, Langlois M, Wang TC (2004). "Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elements.". J. Biol. Chem. 279 (10): 8684–93. doi:10.1074/jbc.M308278200. PMID 14670968.
• Raychowdhury R, Fleming JV, McLaughlin JT, et al. (2002). "Identification and characterization of a third gastrin response element (GAS-RE3) in the human histidine decarboxylase gene promoter.". Biochem. Biophys. Res. Commun. 297 (5): 1089–95. doi:10.1016/S0006-291X(02)02345-8. PMID 12372397.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Sköldberg F, Portela-Gomes GM, Grimelius L, et al. (2003). "Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells.". J. Clin. Endocrinol. Metab. 88 (4): 1445–52. doi:10.1210/jc.2002-021761. PMID 12679420.
• Brew O, Lakasing L, Sullivan M (2007). "Differential activity of histidine decarboxylase in normal and pre-eclamptic placentae.". Placenta 28 (5-6): 585–7. doi:10.1016/j.placenta.2006.05.003. PMID 16822545.
• Zhang F, Xiong DH, Wang W, et al. (2006). "HDC gene polymorphisms are associated with age at natural menopause in Caucasian women.". Biochem. Biophys. Res. Commun. 348 (4): 1378–82. doi:10.1016/j.bbrc.2006.08.008. PMC 1803761. PMID 16919600.
• Tippens AS, Gruetter CA (2004). "Detection of histidine decarboxylase mRNA in human vascular smooth muscle and endothelial cells.". Inflamm. Res. 53 (6): 215–6. doi:10.1007/s00011-004-1252-6. PMID 15167966.
• Siezen CL, Bont L, Hodemaekers HM, et al. (2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.". Pediatr. Infect. Dis. J. 28 (4): 333–5. doi:10.1097/INF.0b013e31818e2aa9. PMID 19258923.
• Morgan TK, Montgomery K, Mason V, et al. (2006). "Upregulation of histidine decarboxylase expression in superficial cortical nephrons during pregnancy in mice and women.". Kidney Int. 70 (2): 306–14. doi:10.1038/sj.ki.5001553. PMID 16760908.
• Papadopoulou N, Kalogeromitros D, Staurianeas NG, et al. (2005). "Corticotropin-releasing hormone receptor-1 and histidine decarboxylase expression in chronic urticaria.". J. Invest. Dermatol. 125 (5): 952–5. doi:10.1111/j.0022-202X.2005.23913.x. PMID 16297195.
• Janssen R, Bont L, Siezen CL, et al. (2007). "Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.". J. Infect. Dis. 196 (6): 826–34. doi:10.1086/520886. PMID 17703412.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Aichberger KJ, Mayerhofer M, Vales A, et al. (2006). "The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells.". Blood 108 (10): 3538–47. doi:10.1182/blood-2005-12-028456. PMID 16849647.
• Lee JK, Kim HT, Cho SM, et al. (2003). "Characterization of 458 single nucleotide polymorphisms of disease candidate genes in the Korean population.". J. Hum. Genet. 48 (5): 213–6. doi:10.1007/s10038-003-0011-9. PMID 12768436.
• Jeong HJ, Moon PD, Kim SJ, et al. (2009). "Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.". Cell. Mol. Life Sci. 66 (7): 1309–19. doi:10.1007/s00018-009-9001-1. PMID 19266161.

External links

• Histidine Decarboxylase at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.