// Workers AI · dad joke modeIs (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate a party animal? It's a compound interest.
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| Names | |
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| Preferred IUPAC name
(2E)-4-Hydroxy-3-methylbut-2-en-1-yl trihydrogen diphosphate | |
| Other names
(E)-4-hydroxy-dimethylallyl pyrophosphate HDMAPP (E)-4-Hydroxy-3-methyl-but-2-enyl diphosphate HMBDP | |
| Identifiers | |
3D model (JSmol) |
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PubChem CID |
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| Properties | |
| C5H12O8P2 | |
| Molar mass | 262.091 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis.[1][2] The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
Biochemical role
[edit]HMB-PP is an intermediate in the non-mevalonate pathway for the biosynthesis of the isoprenoid precursors isopentenyl pyrophosphate and dimethylallyl pyrophosphate.[3][4] Most gram-negative bacteria, the photosynthetic cyanobacteria and green algae use only this pathway, while higher plants also use the mevalonate pathway.[1][5]
The enzyme 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase uses two reduced ferredoxin proteins per molecule of the precursor MEcPP to convert it to HMB-PP:[6][7]
The final step in the non-mevalonate pathway is carried out by the enzyme 4-hydroxy-3-methylbut-2-enyl diphosphate reductase, which gives a mixture of dimethylallyl pyrophosphate and isopentenyl pyrophosphate in the ratio of five to one.[8][9]
The products are then used in terpenoid biosynthesis.[3]
HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis as well as in malaria parasites, but is absent from the human host.[3]
HMB-PP is the physiological activator ("phosphoantigen") for human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood. With a bioactivity of 0.1 nM it is 10,000-10,000,000 times more potent than any other natural compound, such as IPP or alkyl amines. HMB-PP functions in this capacity by binding the B30.2 domain of BTN3A1.[10]
References
[edit]- 1 2 Rohmer, M; Rohmer, Michel (1999). "The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants". Natural Product Reports. 16 (5): 565–74. doi:10.1039/a709175c. PMID 10584331.
- ↑ Fox, DT; Poulter, CD (2002). "Synthesis of (E)-4-hydroxydimethylallyl diphosphate. An intermediate in the methyl erythritol phosphate branch of the isoprenoid pathway". The Journal of Organic Chemistry. 67 (14): 5009–10. doi:10.1021/jo0258453. PMID 12098326.
- 1 2 3 Eisenreich, W; Bacher, A; Arigoni, D; Rohdich, F (2004). "Biosynthesis of isoprenoids via the non-mevalonate pathway". Cellular and Molecular Life Sciences. 61 (12): 1401–26. doi:10.1007/s00018-004-3381-z. PMC 11138651. PMID 15197467. S2CID 24558920.
- ↑ Hunter, WN (2007). "The Non-mevalonate Pathway of Isoprenoid Precursor Biosynthesis". Journal of Biological Chemistry. 282 (30): 21573–21577. doi:10.1074/jbc.R700005200. PMID 17442674.
- ↑ Vranová, Eva; Coman, Diana; Gruissem, Wilhelm (2013-04-29). "Network Analysis of the MVA and MEP Pathways for Isoprenoid Synthesis". Annual Review of Plant Biology. 64 (1): 665–700. Bibcode:2013AnRPB..64..665V. doi:10.1146/annurev-arplant-050312-120116. ISSN 1543-5008. PMID 23451776.
- ↑ Hecht, Stefan; Eisenreich, Wolfgang; Adam, Petra; Amslinger, Sabine; Kis, Klaus; Bacher, Adelbert; Arigoni, Duilio; Rohdich, Felix (2001). "Studies on the nonmevalonate pathway to terpenes: The role of the GcpE (IspG) protein". Proceedings of the National Academy of Sciences. 98 (26): 14837–14842. doi:10.1073/pnas.201399298. PMC 64945. PMID 11752431.
- ↑ Okada, Ken; Hase, Toshiharu (2005). "Cyanobacterial Non-mevalonate Pathway". Journal of Biological Chemistry. 280 (21): 20672–20679. doi:10.1074/jbc.M500865200. PMID 15792953.
- ↑ Charon, L.; Pale-Grosdemange, C.; Rohmer, M. (1999). "On the reduction steps in the mevalonate independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in the bacterium Zymomonas mobilis". Tetrahedron Lett. 40 (40): 7231–7234. doi:10.1016/s0040-4039(99)01531-2.
- ↑ Röhrich RC, Englert N, Troschke K, Reichenberg A, Hintz M, Seeber F, Balconi E, Aliverti A, Zanetti G, Köhler U, Pfeiffer M, Beck E, Jomaa H, Wiesner J (November 2005). "Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum". FEBS Letters. 579 (28): 6433–8. doi:10.1016/j.febslet.2005.10.037. PMID 16289098.
- ↑ Rhodes DA, Chen HC, Price AJ, Keeble AH, Davey MS, James LC, Eberl M, Trowsdale J (2015). "Activation of human γδ T cells by cytosolic interactions of BTN3A1 with soluble phosphoantigens and the cytoskeletal adaptor Periplakin". J Immunol. 194 (5): 2390–8. doi:10.4049/jimmunol.1401064. PMC 4337483. PMID 25637025.
External links
[edit]- 4-hydroxy-3-methylbut-2-enyl+pyrophosphate at the U.S. National Library of Medicine Medical Subject Headings (MeSH)