Biology:Histidine decarboxylase

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Short description: Enzyme that converts histidine to histamine
Histidine Decarboxylase
HDC 3d Ray Image.png
Cartoon depiction of C-truncated HDC dimer with PLP residing in active site.
Identifiers
EC number4.1.1.22
CAS number9024-61-7
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

The enzyme histidine decarboxylase (EC 4.1.1.22, HDC) is transcribed on chromosome 15, region q21.1-21.2, and catalyzes the decarboxylation of histidine to form histamine. In mammals, histamine is an important biogenic amine with regulatory roles in neurotransmission, gastric acid secretion and immune response.[1][2] Histidine decarboxylase is the sole member of the histamine synthesis pathway, producing histamine in a one-step reaction. Histamine cannot be generated by any other known enzyme.[citation needed] HDC is therefore the primary source of histamine in most mammals and eukaryotes. The enzyme employs a pyridoxal 5'-phosphate (PLP) cofactor, in similarity to many amino acid decarboxylases.[3][4] Eukaryotes, as well as gram-negative bacteria share a common HDC, while gram-positive bacteria employ an evolutionarily unrelated pyruvoyl-dependent HDC.[5] In humans, histidine decarboxylase is encoded by the HDC gene.[2][6]

Structure

File:HDC Active Site Diagram.tif Histidine decarboxylase is a group II pyridoxal-dependent decarboxylase, along with aromatic-L-amino-acid decarboxylase, and tyrosine decarboxylase. HDC is expressed as a 74 kDa polypeptide which is not enzymatically functional.[7][8] Only after post-translational processing does the enzyme become active. This processing consists of truncating much of the protein's C-terminal chain, reducing the peptide molecular weight to 54 kDa.

Histidine decarboxylase exists as a homodimer, with several amino acids from the respective opposing chain stabilizing the HDC active site. In HDC's resting state, PLP is covalently bound in a Schiff base to lysine 305, and stabilized by several hydrogen bonds to nearby amino acids aspartate 273, serine 151 and the opposing chain's serine 354.[7] HDC contains several regions that are sequentially and structurally similar to those in a number of other pyridoxal-dependent decarboxylases.[9] This is particularly evident in the vicinity of the active site lysine 305.[10]

Mechanism

File:HDC mechanism.tifHDC decarboxylates histidine through the use of a PLP cofactor initially bound in a Schiff base to lysine 305.[11] Histidine initiates the reaction by displacing lysine 305 and forming an aldimine with PLP. Then, histidine's carboxyl group leaves the substrate, forming carbon dioxide. This is the rate-limiting step of the all process, requiring an activation energy of 17.6 kcal/mol [12] and fitting the experimental turnover of 1.73 [math]\ce{ s^{-1} }[/math].[13] After the decarboxylation takes place, the PLP intermediate is protonated by tyrosine 334 from the second subunit. The protonation is mediated by a water molecule and it is very fast and also very exergonic.[12] Finally, PLP re-forms its original Schiff base at lysine 305, and histamine is released. This mechanism is very similar to those employed by other pyridoxal-dependent decarboxylases. In particular, the aldimine intermediate is a common feature of all known PLP-dependent decarboxylases.[14] HDC is highly specific for its histidine substrate.[15]

Biological relevance

Histidine decarboxylase is the primary biological source of histamine. Histamine is an important biogenic amine that moderates numerous physiologic processes. There are four different histamine receptors, H1, H2, H3, and H4,[16] each of which carries a different biological significance. H1 modulates several functions of the central and peripheral nervous system, including circadian rhythm, body temperature and appetite.[17] H2 activation results in gastric acid secretion and smooth muscle relaxation.[18][19] H3 controls histamine turnover by feedback inhibition of histamine synthesis and release.[20] Finally, H4 plays roles in mast cell chemotaxis and cytokine production.[17]

In humans, HDC is primarily expressed in mast cells and basophil granulocytes. Accordingly, these cells contain the body's highest concentrations of histamine granules. Non-mast cell histamine is also found in the brain, where it is used as a neurotransmitter.[21]

Inhibition

HDC can be inhibited by α-fluoromethylhistidine and histidine methyl ester.[22][23]

Clinical significance

Antihistamines are a class of medications designed to reduce unwanted effects of histamine in the body. Typical antihistamines block specific histamine receptors, depending on what physiological purpose they serve. For example, diphenhydramine (Benadryl™), targets and inhibits the H1 histamine receptor to relieve symptoms of allergic reactions.[24] Inhibitors of histidine decarboxylase can conceivably be used as atypical antihistamines. Tritoqualine, as well as various catechins, such as epigallocatechin-3-gallate, a major component of green tea, have been shown to target HDC and histamine-producing cells, reducing histamine levels and providing anti-inflammatory, anti-tumoral, and anti-angiogenic effects.[25]

Mutations in the gene for Histidine decarboxylase have been observed in one family with Tourette syndrome (TS) and are not thought to account for most cases of TS.[26]

See also

References

  1. ↑ "Studies on bacterial amino-acid decarboxylases: 4. l(-)-histidine decarboxylase from Cl. welchii Type A". The Biochemical Journal 39 (1): 42–6. 1945. doi:10.1042/bj0390042. PMID 16747851. 
  2. ↑ 2.0 2.1 "Entrez Gene: histidine decarboxylase". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3067. 
  3. ↑ "Histidine decarboxylase of Lactobacillus 30a. IV. The presence of covalently bound pyruvate as the prosthetic group". Biochemistry 7 (10): 3520–8. October 1968. doi:10.1021/bi00850a029. PMID 5681461. 
  4. ↑ "Purification and properties of histidine decarboxylase from Lactobacillus 30a". Proceedings of the National Academy of Sciences of the United States of America 54 (1): 152–8. July 1965. doi:10.1073/pnas.54.1.152. PMID 5216347. Bibcode: 1965PNAS...54..152R. 
  5. ↑ "Induction of the histidine decarboxylase genes of Photobacterium damselae subsp. damselae (formally P. histaminum) at low pH". Journal of Applied Microbiology 107 (2): 485–97. August 2009. doi:10.1111/j.1365-2672.2009.04223.x. PMID 19302297. 
  6. ↑ "Preparation of a rat brain histidine decarboxylase (HDC) cDNA probe by PCR and assignment of the human HDC gene to chromosome 15". Human Genetics 90 (3): 235–8. November 1992. doi:10.1007/bf00220068. PMID 1487235. 
  7. ↑ 7.0 7.1 7.2 "Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase". The Journal of Biological Chemistry 287 (34): 29175–83. August 2012. doi:10.1074/jbc.M112.381897. PMID 22767596. 
  8. ↑ Nitta, Yoko (2010). "Expression of recombinant human histidine decarboxylase with full length and C-terminal truncated forms in yeast and bacterial cells". J. Biol. Macromol. 10. http://www.jsb.gr.jp/jbm/2010/1003_1.pdf. 
  9. ↑ Jackson, F. Rob (1990-10-01). "Prokaryotic and eukaryotic pyridoxal-dependent decarboxylases are homologous" (in en). Journal of Molecular Evolution 31 (4): 325–329. doi:10.1007/BF02101126. ISSN 0022-2844. PMID 2124279. Bibcode: 1990JMolE..31..325J. 
  10. ↑ "Multiple evolutionary origin of pyridoxal-5'-phosphate-dependent amino acid decarboxylases". European Journal of Biochemistry 221 (3): 997–1002. May 1994. doi:10.1111/j.1432-1033.1994.tb18816.x. PMID 8181483. 
  11. ↑ 11.0 11.1 "Inhibitory and structural studies of novel coenzyme-substrate analogs of human histidine decarboxylase". FASEB Journal 22 (3): 890–7. March 2008. doi:10.1096/fj.07-9566com. PMID 17965265. http://www.fasebj.org/content/22/3/890. 
  12. ↑ 12.0 12.1 "The Catalytic Mechanism of the Pyridoxal-5'-phosphate-Dependent Enzyme, Histidine Decarboxylase: A Computational Study". Chemistry: A European Journal 23 (38): 9162–9173. July 2017. doi:10.1002/chem.201701375. PMID 28613002. 
  13. ↑ "Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase". The Journal of Biological Chemistry 287 (34): 29175–83. August 2012. doi:10.1074/jbc.m112.381897. PMID 22767596. 
  14. ↑ "Pyridoxal phosphate-dependent decarboxylase". http://www.ebi.ac.uk/interpro/entry/IPR002129. 
  15. ↑ "Reaction specificity in pyridoxal phosphate enzymes". Archives of Biochemistry and Biophysics. Highlight issue on Enzyme Mechanisms 433 (1): 279–87. January 2005. doi:10.1016/j.abb.2004.09.037. PMID 15581583. 
  16. ↑ Jutel, M.; Akdis, M.; Akdis, C. A. (2009-11-13). "Histamine, histamine receptors and their role in immune pathology". Clinical & Experimental Allergy 39 (12): 1786–1800. doi:10.1111/j.1365-2222.2009.03374.x. ISSN 0954-7894. http://dx.doi.org/10.1111/j.1365-2222.2009.03374.x. 
  17. ↑ 17.0 17.1 "International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors". Pharmacological Reviews 67 (3): 601–55. July 2015. doi:10.1124/pr.114.010249. PMID 26084539. 
  18. ↑ "Antihistaminic, anti-inflammatory, and antiallergic properties of the nonsedating second-generation antihistamine desloratadine: a review of the evidence". The World Allergy Organization Journal 4 (2): 47–53. February 2011. doi:10.1097/WOX.0b013e3182093e19. PMID 23268457. PMC 3500039. http://www.waojournal.org/content/4/2/47/abstract. 
  19. ↑ Hill, S.J. (1997). "Classification of Histamine Receptors". Pharmacological Reviews 49: 253–278. http://pharmrev.aspetjournals.org/content/49/3/253. 
  20. ↑ "Identification of two H3-histamine receptor subtypes". Molecular Pharmacology 38 (5): 610–3. November 1990. PMID 2172771. 
  21. ↑ "Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?" (in en). Frontiers in Systems Neuroscience 6: 33. 2012-01-01. doi:10.3389/fnsys.2012.00033. PMID 22586376. 
  22. ↑ "Bioanalysis and disposition of alpha-fluoromethylhistidine, a new histidine decarboxylase inhibitor". Journal of Pharmaceutical Sciences 74 (8): 871–5. August 1985. doi:10.1002/jps.2600740814. PMID 4032273. 
  23. ↑ "Histidine decarboxylase of Lactobacillus 30a: inactivation and active-site labeling by L-histidine methyl ester". Biochemistry 15 (19): 4180–5. September 1976. doi:10.1021/bi00664a008. PMID 963031. 
  24. ↑ "Diphenhydramine Hydrochloride". https://www.drugs.com/monograph/diphenhydramine-hydrochloride.html. 
  25. ↑ "Targeting of histamine producing cells by EGCG: a green dart against inflammation?". Journal of Physiology and Biochemistry 66 (3): 265–70. September 2010. doi:10.1007/s13105-010-0033-7. PMID 20652470. 
  26. ↑ "Online Mendelian Inheritance in Man: histidine decarboxylase". https://www.ncbi.nlm.nih.gov/omim/142704. 

Further reading

External links

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



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