Pyrroloquinoline quinone

Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor and antioxidant.<ref>Template:Cite journal</ref>

Quinoprotein glucose dehydrogenase is used as a glucose sensor in bacteria. PQQ stimulates growth in bacteria.<ref>Template:Cite journal</ref>

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).<ref>Template:Cite journal</ref> Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase. In 1979, Salisbury and colleagues<ref>Template:Cite journal</ref> as well as Duine and colleagues<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>

Biosynthesis

Template:Further A novel aspect of PQQ is its biosynthesis in bacteria from a ribosomally translated precursor peptide, PqqA (UniProt Template:UniProt).<ref name="pmid1310505">Template:Cite journal</ref> A glutamic acid and a tyrosine in PqqA are cross-linked by the radical SAM enzyme PqqE (Template:UniProt) with the help of PqqD (Template:UniProt) in the first step of PqqA modification.<ref name="pmid21223593" /> A protease then liberates the Glu-Tyr molecule from the peptide backbone. PqqB (Template:UniProt) oxidizes the 2 and 3 positions on the tyrosine ring, forming a quinone which quickly becomes AHQQ, finishing the pyridine ring. PqqC (Template:UniProt) then forms the final pyrrole ring.<ref name="pmid32731194">Template:Cite journal</ref>

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 (Template:UniProt).<ref name="pmid21223593">Template:Cite journal</ref>

Role in proteins

Quinoproteins generally embed the cofactor in a unique, six-bladed<ref name="pmid31604769"/> beta-barrel structure. Some examples also have a heme C prosthetic group and are termed quinohemoproteins.<ref>Template:Cite journal</ref> Although quinoproteins are mostly found in bacteria, a Coprinopsis cinerea (fungus) pyranose dehydrogenase has been shown to use PQQ in its crystal structure.<ref name="pmid31604769">Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite journal</ref>

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.<ref name="Ames">Template:Cite journal</ref>

See also

• L-aminoadipate-semialdehyde dehydrogenase, Template:EC number<ref name="BRENDA PQQ EC1.2.1.31 Homo sapiens">Template:Cite encyclopedia</ref><ref name="PQQ HMDB">Template:Cite web citing:
• Template:Cite journal: "Enzymes containing PQQ are called quinoproteins. PQQ and quinoproteins play a role in the redox metabolism and structural integrity of cells and tissues."
• Template:Cite journal: "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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