PQQ can act as a cofactor and antioxidant. It is a quinone like coenzyme Q10/ ubiquinone and can also take up 2 hydrogen, forming PQQH2. The whole PQQ-issue seems a bit disputed. While some studies name several PQQ-dependent enzymes, others say that no enzymes with PQQ as cofactor in mammals have conclusively been identified yet.
Possible PQQ-dependent enzymes:
- choline dehydrogenase, which converts choline to betaine. Betaine can transfer a methylgroup to homocysteine to form methionine.
- amine oxidase
- diamine oxidase (DAO), important for histamine breakdown
- DOPA decarboxylase, which converts L-DOPA to dopamine and dopamine beta-dehydroxylase which breaks down dopamine to norepinephrine
- lysyl oxidase
Apart from choline dehydrogenase, these enzymes have copper as cofactor (1).
I’ve also been looking into whether increased function of the middle-pathway in the methylation cycle might increase formyl-THF levels. Choline breakdown via methionine cycle produces formaldehyde which can be converted to formate and produce formyl-THF from THF (full pathways here). Formyl-THF is a cofactor in the purine synthesis (GMP, AMP). I might update on this issue.
A study found evidence of PQQ-dependent lactate dehydrogenase in mammals (2). PQQ can take up 2H+ and 2e- from NADH/H+. This raises NAD+ levels and PQQH2 and increases the reaction from lactate to pyruvate (NAD+ + lactate -> NADH/H+ + pyruvate). In the study, PQQ caused reduction of cellular lactate release and an increase in intracellular ATP levels in mouse fibroblasts, maybe due to increased activation of the citric acid cycle and oxidative phosphorylation. I’m unsure of whether PQQ really is a bound cofactor of lactate dehydrogenase (in all lactate dehydrogenases, what types,..?), but PQQ certainly seems to have the capacity to increase NAD+ and reduce lactate.
In animal trials, PQQ-deprived rats were found to have increased plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations (3). Also, PQQ deficiency has been shown to lower the activity of succinic acid dehydrogenase and cytochrome c oxidase in rats, two enzymes in the respiratory chain (4,5). Supplementing with PQQ also raised citrate synthase activity. Citrate synthase forms citrate from acetyl-CoA and oxaloacetate. Acetyl-CoA can also be converted to ketone bodies, so decreased citric acid synthase activity and high acetyl-CoA might lead to higher ketone body synthesis.
In a study on how PQQ influences transcriptional factors, changes in thioredoxin-related transcripts were observed. Thioredoxins are proteins that have disulfide-bonds and are involved in S-glutathionylation and deglutathionylation, which protects thiol groups (-SH/ sulfur-hydrogen-group) of proteins from oxidation (I’m still looking into that issue.) (4).
PQQ has been shown to increase the synthesis of new mitochondria by activating PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) and the cAMP response element-binding protein (CREB) (5).
Exercise and mitochondrial biogenesis
The formation of new mitochondria is one of the most profound effects of exercise. Mitochondrial content increases by up to 50% in untrained individuals after 6-8 weeks training. Mitochondrial content is closely linked to endurance capacity during exercise and to increased fat utilization and decreased lactate formation in submaximal exercise. PGC-1α is the main key regulator of mitochondrial biogenesis (6).
PQQ in foods
PQQ is found in various foods. Higher levels of PQQ are found in green pepper, tofu, coke and kiwi fruit. Here is a list with PQQ content in a number of foods.
PQQ is a strong antioxidant and can increase methylation. Studies have also shown that PQQ positively affects enzymes in the respiratory chain. Increased ATP might help calcium signaling by transporting calcium back out of the cytosol and into the endoplasmatic reticulum, from where it can be excreted into the mitochondria and cytosol.
PQQ can reduce lactate production and increase the formation of new mitochondria. Both of these factors are important in exercise tolerance. Also, low PQQ might play a role in immune dysfunction (5). I might look into that further.
I think PQQ has potential as an important cofactor, but I am not quite clear about its main effects yet and am trying to fit it in with other supplements.
Update: Not taking PQQ. It raised my energy levels a bit, but also made me feel more stressed out and worsened my skin symptoms a bit.