Pyrroloquinoline quinone nutritional status alters lysine metabolism and modulates mitochondrial DNA content in the mouse and rat

Department of Nutrition, College of Agriculture and Environmental Sciences, 3135 Meyer Hall, One Shields Avenue, UC Davis, Davis CA 95616, USA.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 12/2006; 1760(11):1741-8. DOI: 10.1016/j.bbagen.2006.07.009
Source: PubMed


Pyrroloquinoline quinone (PQQ) added to purified diets devoid of PQQ improves indices of perinatal development in rats and mice. Herein, PQQ nutritional status and lysine metabolism are described, prompted by a report that PQQ functions as a vitamin-like enzymatic cofactor important in lysine metabolism (Nature 422 [2003] 832). Alternatively, we propose that PQQ influences lysine metabolism, but by mechanisms that more likely involve changes in mitochondrial content. PQQ deprivation in both rats and mice resulted in a decrease in mitochondrial content. In rats, alpha-aminoadipic acid (alphaAA), which is derived from alpha-aminoadipic semialdehyde (alphaAAS) and made from lysine in mitochondria, and the plasma levels of amino acids known to be oxidized in mitochondria (e.g., Thr, Ser, and Gly) were correlated with changes in the liver mitochondrial content of PQQ-deprived rats, but not PQQ-supplemented rats. In contrast, the levels of NAD dependent alpha-aminoadipate-delta-semialdehyde dehydrogenase (AASDH), a cytosolic enzyme important to alphaAA production from alphaAAS, was not influenced by PQQ dietary status. Moreover, the levels of U26 mRNA were not significantly changed even when diets differed markedly in PQQ and dietary lysine content. U26 mRNA levels were measured, because of U26's proposed, albeit questionable role as a PQQ-dependent enzyme involved in alphaAA formation.

Download full-text


Available from: Robert B Rucker, Feb 07, 2015
  • Source
    • "Trace 53 levels of PQQ also have been found in human plasma and body tis- 54 sues at levels up to 5.9 ng/g (Suzuki et al., 1990; Kumazawa et al., 55 1992, 1993), and in human breast milk at concentrations ranging 56 from 140 to 180 ng/mL (Mitchell et al., 1999). 57 A number of physiological properties have been attributed to 58 PQQ ranging from a water soluble cofactor (Kasahara and Kato, 59 2003) and redox cycling agent (Paz et al., 1990) to antioxidant/ 60 pro-oxidant effects (He et al., 2003; Ouchi et al., 2009), growth pro- 61 moter (Rucker et al., 2009), protection of neuronal cells and tissues 62 (Murase et al., 1993; Yamaguchi et al., 1993, 1996; Urakami et al., 63 1995–96), and mitochondriogenesis (Bauerly et al., 2006; Stites 64 et al., 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1,000 to 2,000 mg/kg body weight (bw) in male and 500 to 1,000 mg/kg bw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100 mg/kg bw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.
    Preview · Article · Jan 2014 · Regulatory Toxicology and Pharmacology
  • Source
    • "Organisms common to the gut do not produce PQQ in amounts that are easily determined [21]. Moreover, the levels of PQQ in animal tissues are responsive to changes in diet [5] [6] [7] [8] [9] [10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pyrroloquinoline quinone (PQQ) influences energy-related metabolism and neurologic functions in animals. The mechanism of action involves interactions with cell signaling pathways and mitochondrial function. However, little is known about the response to PQQ in humans. Using a crossover study design, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink in two separate studies. In study 1, PQQ was given in a single dose (0.2 mg PQQ/kg). Multiple measurements of plasma and urine PQQ levels and changes in antioxidant potential [based on total peroxyl radical-trapping potential and thiobarbituric acid reactive product (TBAR) assays] were made throughout the period of 48 h. In study 2, PQQ was administered as a daily dose (0.3 mg PQQ/kg). After 76 h, measurements included indices of inflammation [plasma C-reactive protein, interleukin (IL)-6 levels], standard clinical indices (e.g., cholesterol, glucose, high-density lipoprotein, low-density lipoprotein, triglycerides, etc.) and (1)H-nuclear magnetic resonance estimates of urinary metabolites related in part to oxidative metabolism. The standard clinical indices were normal and not altered by PQQ supplementation. However, dietary PQQ exposure (Study 1) resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans.
    Full-text · Article · Dec 2013 · The Journal of nutritional biochemistry
  • Source
    • "In recent years, PQQ has been receiving considerable attention owing to its several interesting physiological functions [7,8]. PQQ stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and an increase in PGC-1α expression [9,10]. In addition, PQQ promotes the regeneration of peripheral and central nerves. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Pyrroloquinoline quinone (PQQ), a tricarboxylic acid, has attracted attention as a growth factor, and its application to supplements and cosmetics is underway. The product used for these purposes is a water-soluble salt of PQQ disodium. Although in the past, PQQ disodiumpentahydrates with a high water concentration were used, currently, low hydration crystals of PQQ disodiumpentahydrates are preferred. Results We prepared a crystal of PQQ disodium trihydrate in a solution of ethanol and water, studied its structure, and analyzed its properties. In the prepared crystal, the sodium atom interacted with the oxygen atom of two carboxylic acids as well as two quinones of the PQQ disodium trihydrate. In addition, the hydration water of the prepared crystal was less than that of the conventional PQQ disodium crystal. From the results of this study, it was found that the color and the near-infrared (NIR) spectrum of the prepared crystal changed depending on the water content in the dried samples. Conclusions The water content in the dried samples was restored to that in the trihydrate crystal by placing the samples in a humid environment. In addition, the results of X-ray diffraction (XRD) and X-ray diffraction-differential calorimetry (XRD-DSC) analyses show that the phase of the trihydrate crystal changed when the crystallization water was eliminated. The dried crystal has two crystalline forms that are restored to the original trihydrate crystals in 20% relative humidity (RH). This crystalline (PQQ disodium trihydrate) is stable under normal environment.
    Full-text · Article · Jun 2012 · Chemistry Central Journal
Show more