Pyrroloquinoline quinone(PQQ) is coenzyme of methanol dehydrogenase. It is the third prothetic group found in membrane tied bacterial dehydrogenase after flavin nucleotide and nicotinamide nucleotide. 

If PQQ is confirmed by WHO, it will be the 14th vitamin. 

PQQ is familiar with water-soluble B vitamins, which exists in almost all food, the content is 3.65-61.0ng/g. (Kumazawa, 1995) The mice lacking PQQ have low reproduction ability(Steinberg, 2003), so it is supposed that PQQ has the same effect on human body. 

There is PQQ in human viscera, testicle, and body fluid. Spleen has the highest content which is 5.9ng/g. (Kumazawa, 1992) The PQQ content and its deviant in human milk are 140-180ng/mL, which is several times of other food. It shows PQQ may play an essential role in growth and development of newborn infants.(Mitchell, 1999)

It is impossible to prove higher organisms are able to self synthesis PQQ. So PQQ in higher organisms is regarded from a germ. Various germs have various PQQ secretion volume which is from 1pg/mL to 1mg/mL. 

The germ in animal intestine and human intestine are unable to synthesis PQQ or the synthesis volume is very low, which is unable to satisfy the needs of the body. Therefore, animals and human need to take PQQ by the way of diet. 

The anti-oxidizing and pro oxidation effect of PQQ

Oxide of reaction between quinones and reactive oxygen species, is able to form compound with glutathione, it consumes dissociative glutathione, which reduces the stress tolerance of cellular oxidation, amounts of proteins are oxidized, which eventually leads to cell death. 

PQQ has the ability to adjust redox point in N-methyl-D-aspartic acid receptor(NMDA). So it is able to anti neuron injury effect mediated by NMDA and glutamate acid.(Aizenman, 1992)

PQQ is in a position to change redox status in cells, and specially kills lymphoma cells(U937). 

When PQQ guides lymphoma cells to death, it will make 2-5 times increasing in volume of N-acetyl-L-cysteine(NAC) and glutathione, it proves PQQ guided cytotoxic effect exceeds its redox regulation. On the one hand, PQQ consumes glutathione in cells, on the other hand, it makes the toxicity magnify several time. Induced mode of PQQ transfers from apoptosis mode to cytoclasis mode, it means PQQ not only can exert oxidation, speedup death process of necrotic cells, but also can speedup cell apoptosis to answer oxidative stress state. (Shankar, 2010)

2. PQQ’s protective effect on neuron

Through the observation of PQQ’s inducing effect on neuron in mice sciatic nerve defect model, it is discovered PQQ treated mice group has maturer and higher concentration regenerative nerve cells. It proves PQQ has strong synergism on peripheral nerve regeneration. In the treatment of mice stroke model, it is proved that PQQ can also increase the respiration rate of mitochondrion in highly ischemic and non ischemic cardiac muscle. PQQ has a regulatory effect 

On mitochondrion're number and function in mice. The antioxidation lead by PQQ can guard against death of neuron in a rodent model of stroke. So it is predicted that PQQ has a neuroprotective effect.

These results show neuron can be controlled by PQQ from neurotoxicity lead by amyloid beta. 

3. PQQ's adjustment function in signal transduction and DNA reparable function 

PQQ is able to activate the Ras signaling pathway in fibroblasts NIH3T3. It could lead to signaling protein phosphorylation. (Kumazawa, 2007) 

Summary from research on proliferation of Schwann cells and Akt-signaling, PQQ can influence the morphology of cells, increase expression of c-Fos, c-Jun, adenosine pyrophosphate responsive elements binding protein, and proliferating cells nuclear antigen(PCNA). PQQ is able to activate Akt pathway of Schwann cells. It means PI3K/Akt signaling pathway may participate in reproduction of Schwann cells, and also adjusted by PQQ. There are researches show PQQ can influence other signal pathway to adjust in vivo hepatocytes, and increases the rate of apoptosis of U937 tumor cells. 

As periplasm protein kinase revulsion in germ, PQQ can take part in biosynthesis of cell membranes, E.coli cooperative accomplishment of pathogenicity.(Khairnar, 2007) 

4. PQQ’s regulation of gene expression and protein function 

PQQ is an essential nutrient elements.  Intake of PQQ or intracellular production of PQQ can accelerate creature growth and improve stress tolerance. 

In the study on mechanisms of PQQ in growth and resistance area, it shows PQQ is in a position to mediate the transcription and translation of proteins by phosphorylation. It can inhibit the melanin synthesis of melanoma cells. It means PQQ act a direct action in gene expression.(Satok, 2009)

The existence of PQQ also acts directly at the expression of the tyrosinase gene and TRP-2 gene. The celiac injection of PQQ in mice can inhibit the synthesis of nitric oxide synthase in mRNA transcription in damaged spinal cord, so it can efficiently promote the functional recovery of spinal cord damage. (Hirakawa, 2009)

Safety and dose

PQQ is similar to quinones antioxidant. Its effects depend on the concentration. PQQ plays a role as anti-oxidation when the concentration is below 10μmol/L, and as pro oxidation.(He Kai, 2003) Compared with metoprolol. It is more effective in protection of mitochondrion and oxidative damage caused by ischemia repercussion. (ZHU Baoquan, 2006)

Within 3 hours after artery occlusion in reversible brain, with an implantation dose of 10mg/kg PQQ, brain infarct area can be reduced effectively in 72 hours.(Kim, 2010)

With 6μg/kg additions PQQ in food of BALB/c mice, its growth speed and fecundity can be improved, and extracellular matrix index can be adjusted. (Steinberg, 2003)

Reference:

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Khairnar N P, Kamble V A, Mangoli S H, et al. Involvement of a periplasmic protein kinase in DNA strand break repair and homologous recombination in Escherichia coli[J]. Molecular Microbiology, 2007, 65(2):294-304.

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Kumazawa T, Sato K, Seno H, et al. Levels of pyrroloquinoline quinone in various foods.[J]. Biochemical Journal, 1995, 307 ( Pt 2):331-333.

KUMAZAWA T, SENO H, URAKAMI T, et al. Trace levels of pyrroloquinoline quinone in human and rat samples edteceted by gas chromatoraphy/mass spectrometry[J]. Biochimica et Biophysica Acta (BBA)-General Subjects, 1992, 1156(1): 62-66

Mitchell A E, Jones A D, Mercer R S, et al. Characterization of Pyrroloquinoline Quinone Amino Acid Derivatives by Electrospray Ionization Mass Spectrometry and Detection in Human Milk ☆[J]. Analytical Biochemistry, 1999, 269(2):317-325..

Sato K, Toriyama M. Effect of pyrroloquinoline quinone (PQQ) on melanogenic protein expression in murine B16 melanoma.[J]. Journal of Dermatological Science, 2009, 53(2):140-5.

Shankar B S, Pandey R, Amin P, et al. Role of glutathione in augmenting the anticancer activity of pyrroloquinoline quinone (PQQ).[J]. Redox Report Communications in Free Radical Research, 2010, 15(15):146-54.

Steinberg F, Stites T E, Anderson P, et al. Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets.[J]. Experimental Biology & Medicine, 2003, 228(2):160-6.