Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor and antioxidant.[1]
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| 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 |
|
| 56633 | |
| KEGG | |
| MeSH | PQQ+Cofactor |
PubChem CID | |
| UNII | |
CompTox Dashboard (EPA) | |
| |
| |
| 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). | |
Quinoprotein glucose dehydrogenase is used as a glucose sensor in bacteria. PQQ stimulates growth in bacteria.[2]
History
It was discovered by J. G. Hauge 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. It 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 the 2003 paper by Kasahara and Kato that essentially stated that PQQ was a new vitamin and in 2005, an article by Anthony and Felton that stated that the 2003 Kasahara and Kato paper drew incorrect and unsubstantiated conclusions.[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.[14]