A novel aspect of PQQ is its biosynthesis in bacteria from a ribosomally translated precursor peptide, PqqA (UniProtP27532).[7] Aglutamic acid and atyrosine in PqqA are cross-linked by theradical SAMenzyme 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 thepyridine ring. PqqC (P07780) then forms the finalpyrrole 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 carriermycofactocin, using avaline and atyrosine from the precursor peptide, MftA (P9WJ81).[8]
Quinoproteins generally embed the cofactor in a unique, six-bladed[10]beta-barrel structure. Some examples also have aheme C prosthetic group and are termed quinohemoproteins.[11] Although quinoproteins are mostly found in bacteria, aCoprinopsis 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 mammalianlactate dehydrogenase requires PQQ to run but usesNADH as the direct redox cofactor. PQQ seems to speed up the reaction by catalyzing the oxidation of NADH via redox cycling.[12]
The scientific journalNature 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 byBruce Ames inThe 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]
^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.PMID30526470.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^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.PMID2855583.
^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.PMID222269.
^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.PMID11831471.S2CID12469203.
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.PMID2558842.{{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.PMID12712191.: "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."
