A novel aspect of PQQ is its biosynthesis in bacteria from a ribosomally translated precursor peptide, PqqA (UniProtP27532).[7]Aglutamic acid and a tyrosine in PqqA are cross-linked by the radical 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 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]
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]
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 AmesinThe 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]
^Wen H, He Y, Zhang K, Yang X, Hao D, Jiang Y, He B. Mini-review: Functions and Action Mechanisms of PQQ in Osteoporosis and Neuro Injury. Curr Stem Cell Res Ther. 2020;15(1):32-36. doi:10.2174/1574888X14666181210165539PMID30526470
^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. doi:10.1016/0006-291X(79)92018-7. PMID222269.
PMID2558842: "Enzymes containing PQQ are called quinoproteins. PQQ and quinoproteins play a role in the redox metabolism and structural integrity of cells and tissues."
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."
