Recent progress in studies on the health benefits of pyrroloquinoline quinone

Figures & data

Fig. 1. Structure and redox reaction of pyrroloquinoline quinone (PQQ).

Fig. 2. Proposed mechanism for the ligand-independent activation of epidermal growth factor receptor (EGFR) signaling through redox cycling of pyrroloquinoline quinone (PQQ). PQQ undergoes redox cycling in the presence of reductants, such as ascorbate and glutathione, and then produces ${\text{O}}_2^{-}$ and H₂O₂. The generated H₂O₂ inactivates protein tyrosine phosphatase 1B (PTP1B) via the oxidation of catalytic cysteinyl thiol (Cys-215) to the corresponding sulfenic acid (–SOH), sulfinic acid (–SO₂H), and sulfonic acid (–SO₃H). The inhibition of PTP1B evokes the EGF-independent activation (tyrosine phosphorylation) of EGFR and subsequent activation (serine/threonine phosphorylation) of ERK 1/2.

Fig. 3. Pyrroloquinoline quinone (PQQ)-induced activation of cAMP-responsive element-binding protein (CREB)-peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and insulin signaling. (A) Proposed mechanism for PQQ-induced activation of CREB-PGC-1α signaling pathway. PQQ stimulates the phosphorylation and activation of CREB and enhances PGC-1α expression. Increased PGC-1α binds to and coactivates the transcriptional function of nuclear respiratory factor (NRF)-1/2 on the mitochondrial transcription factor A (Tfam) promoter. Tfam plays a crucial role in regulating mtDNA amplification and mitochondrial biogenesis. (B) Proposed mechanism for the ligand-independent activation of insulin signaling through redox cycling of PQQ. PQQ inhibits protein tyrosine phosphatase 1B (PTP1B) to oxidatively modify the catalytic cysteine through its redox cycling activity. The inhibition of PTP1B evokes the insulin-independent activation (tyrosine phosphorylation) of the insulin receptor (IR) and subsequent phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt. Phosphorylated Akt stimulates translocation of glucose transporter 4 (GLUT4) to the plasma membrane, resulting in increased cellular glucose uptake.

Fig. 4. The summary of radical quenching reactions. Pyrroloquinoline quinol (PQQH₂) can be made from pyrroloquinoline quinone (PQQ) by reduction of NADPH, cysteine, and glutathione. Aroxyl radicals, singlet oxygen, and α-tocopheroxyl radicals are quenched by PQQH₂.