吡咯喹啉醌(Pyrroloquinoline quinone，简称PQQ)是一种新辅酶，是继黄素核苷酸和烟酰胺核苷酸之后，在膜束缚的细菌脱氢酶中发现的第三种辅酶。该化合物最先是从细菌中分出来的，随后在动、植物体内也被发现了,它的化学名称为4，5-二氢-4，5-二氧化-1-氢吡咯(2，3f)醌-2，7，9一三羧酸，又名methaxatin。PQQ具有缩短恶臭醋酸杆菌和啤酒酵母菌的迟缓期，刺激烟草种子提早发芽，预防和治疗某些疾病等生物学功能。在原核生物、植物和哺乳动物中，都广泛存在着吡咯喹啉醌，它不仅是许多酶的辅基，在酶促反应中担负着传递电子、质子和化学基团的功能，也能刺激微生物的生长，植物花粉的萌发，促进植物的生长。
近年来, 对于吡咯喹啉醌的分布状况、产生机理、结构、功能和生物学性质研究以及以吡咯喹啉醌作为新药的研究工作在国际上非常很活跃。日本东京农工大学研究人员报道吡咯喹啉醌能够抑制帕金森氏症致病蛋白的凝集。研究人员根据这个基本原理利用帕金森氏症模型动物开展深入研究，开发了改善该疾病症状的药物。科学家们还发现吡咯喹啉醌能够刺激人体细胞生长和有效防治肝损伤。而且，吡咯喹啉醌还具有很强的自由基清除能力，其清除O2•和•OH能力较抗坏血酸高50 ~ 100倍。日本学者于2003年证实PQQ完全符合维生素特征，是一种新型的水溶性维生素，其研究成果发表于国际权威杂志《nature》上。这是55年来首次发现的最新的维生素。在辅酶Q10产业化方面占领导地位的日本Mitsubishi Gas Chemical of Tokyo公司 和美国 Maypro公司，2007年宣布联合推进吡咯喹啉醌在医药和保健行业的产业化进程。
Pyrroloquinoline quinone (PQQ) is an organic molecule found from bacteria as a reduction-oxidization (redox) cofactor, such as nicotinamides (pyridine nucleotides) and flavins. Because mice fed a PQQ-deficient diet showed several abnormalities; they grew slowly, had fragile skin, and showed poor reproductive performance, PQQ was thought to be one of the important nutrients for mammals. However, the biochemical role was unknown.
In the course of the study on bipolar disorder (manic depression), we cloned a novel gene, which was related to the metabolism of lysine, an essential amino acid. Lysine is degraded mainly to 2-aminoadipic 6-semialdehyde (AAS) and subsequently oxidized to 2-aminoadipic acid (AAA). The gene for AAS dehydrogenase catalyzing the oxidation of AAS to AAA has not been found until now. The discovery of the gene led us to identify the new vitamin PQQ.
PQQ-linked enzyme "AAS dehydrogenase"
Based on the the primary structure of the protein that was guessed from the cloned gene, in the latter half (C-terminal) part of the AAS dehydrogenase there exist seven repeats of "PQQ-binding motif". The PQQ-binding motif is commonly found in bacterial PQQ-dependent dehydrogenases. The six to eight tandem repeats of the motif are also present in these PQQ-dependent dehydrogenases, indicating that mouse AAS dehydrogenase could be a PQQ-dependent enzyme. From afterwards analysis, it was proven that the gene for AAS dehydrogenase are widely present not only in mammals such as human but also in other vertebrates, invertebrates, and higher plants such as rice.
PQQ-deprived mice
We examined the effects of a PQQ-deficient diet on mice to see the importance of PQQ in the lysine degradation pathway. As reported, several abnormalities were observed in PQQ-deprived mice; the reproductive performance was low and the lie of fur was bad. We measured the blood levels of lysine and AAA, and found that AAA concentration was significantly decreased in PQQ-deprived mice. This decrease in AAA may be indicative of impaired AAS dehydrogenase, suggesting a requirement for PQQ as a redox cofactor for the proper functioning of AAS dehydrogenase.
PQQ is a new vitamin
Our current results clarifing the biochemical role of PQQ seem to determine for the first time that PQQ is a vitamin for animals. Humans must take nicotinamides and flavins, already-known redox cofactors, from outer sources as vitamin B3 (niacin) and vitamin B2 (riboflavin), respectively. PQQ may also be considered a member of the vitamin B group by its molecular nature and function. PQQ is mostly contained in common foods; comparatively in large quantities in natto (fermented soybeans), tea, papayas, and kiwi fruits. At present, PQQ is not added to medical vitamin tablets (oral agent and parenteral injection) and multi-vitamin supplements. Although it is uncertain whether there are PQQ-depleted humans, PQQ will apply to various scenes as a vitamin.
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