The PQQ story

About twenty years ago, the cofactor pyrroloquinoline quinone, PQQ, was dis covered. Here the author gives his personal view on the reasons why this co factor was so lately discovered and how the steps in its identification wer e made. The discovery not only led to subsequent studies on the physiologic al significance of PQQ but also initiated investigations on other enzymes w here the presence of PQQ was expected, resulting in the discovery of three other quinone cofactors, TPQ, TTQ, and LTQ, which differ from PQQ as they a re part of the protein chain of the enzyme to which they belong. Enzymes us ing quinone cofactors, the so-called quinoproteins, copper-quinoproteins, a nd quinohemoproteins, are mainly involved in the direct oxidation of alcoho ls, sugars, and amines. Some of the PQQ-containing ones participate in inco mplete bacterial oxidation processes like the conversion of ethanol into vi negar and of D-glucose into (5-keto)gluconic acid. Soluble glucose dehydrog enase is the sensor in diagnostic test strips used for glucose determinatio n in blood samples of diabetic patients. Quinohemoprotein alcohol dehydroge nases have an enantiospecificity suited for the kinetic resolution of racem ic alcohols to their enantiomerically pure form, certain enantiomers being interesting candidates as building block for synthesis of high-value-added chemicals. Making up for balance after twenty years of quinoprotein researc h, the following conclusions can be drawn: since quinoproteins do not catal yze unique reactions, we know now that there are more enzymes which catalyz e one and the same reaction than we did before, but do not understand the r eason for this (compare e.g. NAD/NADP-dependent glucose dehydrogenases, fla voprotein glucose oxidase/dehydrogenase, and soluble/membrane-bound, PQQ-co ntaining glucose dehydrogenases, enzymes all catalyzing the oxidation of be ta-D-glucose to delta-gluconolactone but being quite different from each ot her); however, taking a pragmatic point of view, the foregoing can also be regarded as a positive development since as illustrated by the examples giv en above, the enlargement of the catalytic arsenal with quinoprotein enzyme s provides in more possibilities for enzyme applications; the hopes that PQ Q could be a new vitamin have diminished strongly after it has become clear that its occurrance is restricted to bacteria; the impact factor is broade r than just the development of the field of quinoproteins, since together w ith that of enzymes containing a one-electron oxidized amino acid residue a s cofactor, it has emphasized that cofactors not only derive from nucleotid es (e.g. FAD, NAD) but also from amino acids. Finally, strong indications e xist to assume that this is not the end of the story since other quinone co factors seem awaiting their discovery.