Pyrroloquinoline quinone: properties, mechanism of action and applications

General Description

Pyrroloquinoline quinone is a versatile compound with diverse properties. It acts as a redox cofactor, a free radical scavenger, and an amine oxidase catalyst. PQQ participates in redox cycling and exhibits antioxidant activity. It can protect against oxidation and enhance immune function. Pyrroloquinoline quinone affects metabolic regulation and activates antioxidant response genes. It also modulates inflammatory pathways. PQQ has potential health benefits in preventing chronic diseases such as cardiovascular disease, neurodegenerative disorders, and certain types of cancer. However, further research is needed to understand its mechanisms of action and long-term effects. Consult a healthcare professional before considering pyrroloquinoline quinone supplementation.

Figure 1. Pyrroloquinoline quinone

Properties

Pyrroloquinoline quinone is a water-soluble quinone with diverse properties. It serves as a redox cofactor, a free radical scavenger, and an amine oxidase catalyst. PQQ exhibits similarities to ascorbic acid, riboflavin, and pyridoxal-5-phosphate in its chemical features. Both the oxidized and reduced forms of PQQ participate in redox cycling. PQQ’s electrophilic nature enables it to react with various substances, form complexes with different compounds, and produce iminoquinone under specific conditions. Unlike other compounds, pyrroloquinoline quinone shows high efficiency in redox cycling assays and acts as an antioxidant and radical scavenger. It catalyzes continuous redox reactions involving the oxidation of several compounds and can protect α-tocopherol from oxidation. However, oxidized PQQ lacks antioxidant activity in the presence of metals like copper. Additionally, PQQ can catalyze the oxidation of certain proteins and pyridoxamine derivatives. Overall, pyrroloquinoline quinone exhibits unique properties that make it valuable for various biological processes and potential therapeutic applications. ¹

Mechanism of action

Pyrroloquinoline quinone acts as a cofactor for various bacterial enzymes, including glucose or alcohol dehydrogenases. Lupinine hydroxylase is the exception, serving as an amine dehydrogenase with lupinine from lupin plants as the substrate. Mechanisms involving hydride ion transfers and metal ions (K+, Mg2+, Li+, or Ca2+) play catalytic roles in the oxidation of glucose and alcohol substrates. In mammalian dehydrogenases such as lactate dehydrogenase (LDH), PQQ has been found to enhance NADH oxidation to NAD+ and pyruvate production. This optimization of oxidative metabolism is linked to improved antioxidant defense and enhanced immune function. NAD+ serves as a substrate for deacylation reactions catalyzed by sirtuins, particularly SIRT1 and SIRT3, which are essential signaling proteins for metabolic regulation related to oxidative processes. SIRT1 is primarily located in the nucleus and cytoplasm, while SIRT3 is mainly found in the mitochondria and associated with mitochondrial DNA transcription. PGC-lα, a critical factor regulated by sirtuin activity, acts as a transcriptional coactivator to maintain energy homeostasis and activate antioxidant response genes through the assembly of other enhancers like NRF-1 and NRF-2. Dietary supplementation of pyrroloquinoline quinone also affects other transcriptional networks, including AMPK, MAPK, and JAK-STAT pathways, which play roles in cellular proliferation, mitosis, apoptosis, and immune response control. ²

Applications

Pyrroloquinoline quinone is a compound that has gained significant attention in recent years for its potential health benefits and its role in disease prevention. PQQ is a redox cofactor, meaning it plays a critical role in energy metabolism within cells. In terms of health promotion, pyrroloquinoline quinone has been suggested to possess powerful antioxidant properties. Antioxidants help neutralize harmful free radicals in the body, which can cause oxidative stress and damage cells. By reducing oxidative stress, pyrroloquinoline quinone may help protect against chronic diseases such as cardiovascular disease, neurodegenerative disorders, and certain types of cancer. Furthermore, research has indicated that PQQ may have anti-inflammatory properties, which are crucial for maintaining overall health. Chronic inflammation is associated with various diseases, including heart disease, diabetes, and autoimmune disorders. By modulating inflammatory pathways, PQQ may help reduce the risk or severity of these conditions. However, it is important to note that while PQQ shows potential in promoting health and disease prevention, further research is needed to fully understand its mechanisms of action and its long-term effects. As with any supplement or compound, it is advisable to consult with a healthcare professional before starting PQQ supplementation, especially if you have any underlying medical conditions or are taking medication. Overall, pyrroloquinoline quinone holds promise as a versatile compound with potential applications in health promotion and disease prevention, particularly in the areas of antioxidant defense, cognitive function, inflammation modulation, and mitochondrial support. ³

Reference

1. Stites TE, Mitchell AE, Rucker RB. Physiological importance of quinoenzymes and the O-quinone family of cofactors. J Nutr, 2000, 130:719–727.

2. Tchaparian E, Marshal L, Cutler G, Bauerly K, Chowanadisai W, Satre M, Harris C, Rucker RB. Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK/STAT and MAPK pathways. Biochem J, 2010, 429(3):515-526.

3. Jonscher KR, Chowanadisai W, Rucker RB. Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention. Biomolecules, 2021, 11(10):1441.

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