Pyrroloquinoline quinone

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Pyrroloquinoline quinone
Pyrroloquinoline quinone.svg
Names
Systematic IUPAC name
4,5-Dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid
Identifiers
3D model (JSmol)
3596812
ChEBI
ChEMBL
ChemSpider
DrugBank
EC Number
  • 839-691-6
56633
KEGG
MeSH PQQ+Cofactor
PubChem CID
UNII
  • InChI=1S/C14H6N2O8/c17-10-4-2-6(14(23)24)15-8(4)7-3(12(19)20)1-5(13(21)22)16-9(7)11(10)18/h1-2,15H,(H,19,20)(H,21,22)(H,23,24) Yes check.svgY
    Key: MMXZSJMASHPLLR-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C14H6N2O8/c17-10-4-2-6(14(23)24)15-8(4)7-3(12(19)20)1-5(13(21)22)16-9(7)11(10)18/h1-2,15H,(H,19,20)(H,21,22)(H,23,24)
    Key: MMXZSJMASHPLLR-UHFFFAOYAP
  • c1c2c([nH]c1C(=O)O)-c3c(cc(nc3C(=O)C2=O)C(=O)O)C(=O)O
Properties
C14H6N2O8
Molar mass 330.208 g·mol−1
Density 1.963 g/cm3
Hazards
Flash point 569.8 °C (1,057.6 °F; 842.9 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor and antioxidant. [1]

Quinoprotein glucose dehydrogenase is used as a glucose sensor in bacteria. PQQ stimulates growth in bacteria. [2]

History

It was discovered by Jens Gabriel Hauge in 1964 as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone). [3] Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase. In 1979, Salisbury and colleagues [4] as well as Duine and colleagues [5] extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues discovered that PQQ was also found in Acetobacter . [6]

Biosynthesis

A novel aspect of PQQ is its biosynthesis in bacteria from a ribosomally translated precursor peptide, PqqA (UniProt P27532 ). [7] A glutamic acid and a tyrosine in PqqA are cross-linked by the radical SAM enzyme PqqE ( P07782 ) with the help of PqqD ( P07781 ) in the first step of PqqA modification. [8] A protease then liberates the Glu-Tyr molecule from the peptide backbone. PqqB ( P07779 ) oxidizes the 2 and 3 positions on the tyrosine ring, forming a quinone which quickly becomes AHQQ, finishing the pyridine ring. PqqC ( P07780 ) then forms the final pyrrole ring. [9]

Efforts to understand PQQ biosynthesis have contributed to broad interest in radical SAM enzymes and their ability to modify proteins, and an analogous radical SAM enzyme-dependent pathway has since been found that produces the putative electron carrier mycofactocin, using a valine and a tyrosine from the precursor peptide, MftA ( P9WJ81 ). [8]

Role in proteins

Quinoproteins generally embed the cofactor in a unique, six-bladed [10] beta-barrel structure. Some examples also have a heme C prosthetic group and are termed quinohemoproteins. [11] Although quinoproteins are mostly found in bacteria, a Coprinopsis cinerea (fungus) pyranose dehydrogenase has been shown to use PQQ in its crystal structure. [10]

PQQ also appears to be essential in some other eukaryotic proteins, albeit not as the direct electron carrier. The mammalian lactate dehydrogenase requires PQQ to run but uses NADH as the direct redox cofactor. PQQ seems to speed up the reaction by catalyzing the oxidation of NADH via redox cycling. [12]

Controversy regarding role as vitamin

The scientific journal Nature published a 2003 paper by Kasahara and Kato that essentially stated that PQQ was a new vitamin, a cofactor required for the activity of an enzyme they believe to be involved in lysine metabolism (U26). In 2005, an article by Anthony and Felton that stated that the 2003 Kasahara Kato paper drew incorrect and unsubstantiated conclusions. Specifically, the databases used by the paper inappropriately labeled β-propeller sequences as PQQ-binding motifs. [13]

An article by Bruce Ames in The Proceedings of the National Academy of Sciences in 2018 identified pyrroloquinoline quinone as a "longevity vitamin" not essential for immediate survival, but necessary for long-term health. Evidence of this identification include preclinical human studies, animal studies, and cell culture studies. [14]

See also

References

  1. ↑ Wen H, He Y, Zhang K, Yang X, Hao D, Jiang Y, He B (2020). "Mini-review: Functions and Action Mechanisms of PQQ in Osteoporosis and Neuro Injury". Curr Stem Cell Res Ther. 15 (1): 32–36. doi:10.2174/1574888X14666181210165539. PMID   30526470.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ↑ Ameyama M, Matsushita K, Shinagawa E, Hayashi M, Adachi O (1988). "Pyrroloquinoline quinone: excretion by methylotrophs and growth stimulation for microorganisms". BioFactors. 1 (1): 51–3. PMID   2855583.
  3. ↑ Hauge JG (1964). "Glucose dehydrogenase of bacterium anitratum: an enzyme with a novel prosthetic group". J Biol Chem. 239 (11): 3630–9. doi: 10.1016/S0021-9258(18)91183-X . PMID   14257587.
  4. ↑ Salisbury SA, Forrest HS, Cruse WB, Kennard O (1979). "A novel coenzyme from bacterial primary alcohol dehydrogenases". Nature. 280 (5725): 843–4. Bibcode:1979Natur.280..843S. doi:10.1038/280843a0. PMID   471057. S2CID   3094647.
  5. ↑ Westerling J, Frank J, Duine JA (1979). "The prosthetic group of methanol dehydrogenase from Hyphomicrobium X: electron spin resonance evidence for a quinone structure". Biochem Biophys Res Commun. 87 (3): 719–24. Bibcode:1979BBRC...87..719W. doi:10.1016/0006-291X(79)92018-7. PMID   222269.
  6. ↑ Ameyama M, Matsushita K, Ohno Y, Shinagawa E, Adachi O (1981). "Existence of a novel prosthetic group, PQQ, in membrane-bound, electron transport chain-linked, primary dehydrogenases of oxidative bacteria". FEBS Lett. 130 (2): 179–83. Bibcode:1981FEBSL.130..179A. doi: 10.1016/0014-5793(81)81114-3 . PMID   6793395.
  7. ↑ Goosen N, Huinen RG, van de Putte P (1992). "A 24-amino-acid polypeptide is essential for the biosynthesis of the coenzyme pyrrolo-quinoline-quinone". J Bacteriol. 174 (4): 1426–7. doi:10.1128/jb.174.4.1426-1427.1992. PMC   206443 . PMID   1310505.
  8. 1 2 Haft DH (2011). "Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners". BMC Genomics. 12 21. doi: 10.1186/1471-2164-12-21 . PMC   3023750 . PMID   21223593.
  9. ↑ Zhu, W; Klinman, JP (December 2020). "Biogenesis of the peptide-derived redox cofactor pyrroloquinoline quinone". Current Opinion in Chemical Biology. 59: 93–103. doi:10.1016/j.cbpa.2020.05.001. PMC   7736144 . PMID   32731194.
  10. 1 2 Takeda, K; Ishida, T; Yoshida, M; Samejima, M; Ohno, H; Igarashi, K; Nakamura, N (15 December 2019). "Crystal Structure of the Catalytic and Cytochrome b Domains in a Eukaryotic Pyrroloquinoline Quinone-Dependent Dehydrogenase". Applied and Environmental Microbiology. 85 (24): e01692-19. Bibcode:2019ApEnM..85E1692T. doi: 10.1128/AEM.01692-19 . PMC   6881789 . PMID   31604769.
  11. ↑ Matsushita, K; Toyama, H; Yamada, M; Adachi, O (January 2002). "Quinoproteins: structure, function, and biotechnological applications". Applied Microbiology and Biotechnology. 58 (1): 13–22. doi:10.1007/s00253-001-0851-1. PMID   11831471. S2CID   12469203.
  12. ↑ Akagawa, M; Minematsu, K; Shibata, T; Kondo, T; Ishii, T; Uchida, K (27 May 2016). "Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein". Scientific Reports. 6 26723. Bibcode:2016NatSR...626723A. doi:10.1038/srep26723. PMC   4882622 . PMID   27230956.
  13. ↑ Felton LM, Anthony C (2005). "Biochemistry: role of PQQ as a mammalian enzyme cofactor?". Nature. 433 (7025): E10, discussion E11–2. Bibcode:2005Natur.433E..10F. doi: 10.1038/nature03322 . PMID   15689995. S2CID   4370935.
  14. ↑ Ames, Bruce (15 October 2018). "Prolonging healthy aging: Longevity vitamins and proteins". Proceedings of the National Academy of Sciences of the United States of America. 115 (43): 10836–10844. Bibcode:2018PNAS..11510836A. doi: 10.1073/pnas.1809045115 . PMC   6205492 . PMID   30322941.
  15. ↑ "L-aminoadipate-semialdehyde dehydrogenase (Homo sapiens)". BRENDA. Technische Universität Braunschweig. July 2015. Retrieved 18 July 2015.
  16. ↑ "Pyrroloquinoline quinone (HMDB13636)". Human Metabolome Database. University of Alberta. Retrieved 19 July 2015, citing:
    • Paz MA, Flückiger R, Torrelio BM, Gallop PM (1989). "Methoxatin (PQQ), coenzyme for copper-dependent amine and mixed-function oxidation in mammalian tissues". Connect. Tissue Res. 20: 251–7. PMID   2558842.{{cite journal}}: CS1 maint: multiple names: authors list (link): "Enzymes containing PQQ are called quinoproteins. PQQ and quinoproteins play a role in the redox metabolism and structural integrity of cells and tissues."
    • Kasahara T, Kato T (April 2003). "Nutritional biochemistry: A new redox-cofactor vitamin for mammals". Nature. 422: 832. doi:10.1038/422832a. PMID   12712191.: "It was reported that aminoadipate semialdehyde dehydrogenase (AASDH) might also use PQQ as a cofactor, suggesting a possibility that PQQ is a vitamin in mammals."
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