Pyrroloquinoline quinone
Encyclopedia
Pyrroloquinoline quinone (PQQ) was discovered by J.G. Hauge as the third redox cofactor after nicotinamide
and flavin in bacteria (although they hypothesised that it was naphthoquinone
). Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase
and named it methoxatin. In 1979, Salisbury and colleagues as well as Duine and colleagues extracted this prosthetic group from methanol dehydrogenase
of methylotroph
s and identified its molecular structure. Adachi and colleagues identified that PQQ was also found in Acetobacter
.
These enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase
, one of the quinoproteins, is used as a glucose sensor. Subsequently, PQQ was found to stimulate growth in bacteria. In addition, antioxidant and neuro-protective effects were also found.
In 1989, Rucker and colleagues reported that mice deprived of PQQ showed various abnormalities, and it was suggested that PQQ may also have an important nutritional role in other mammals. In 2003, it was reported that aminoadipate semialdehyde dehydrogenase
(AASDH) might also use PQQ as a cofactor, suggesting a possibility that PQQ is a vitamin in mammals. Rucker and colleagues concluded that insufficient information is available so far to state that PQQ is a vitamin for mammals, although PQQ may be an important biological factor.
It was recently shown that PQQ may stimulate growth of plants (cucumbers and tomatoes) in hydroponic culture and may be the causative factor in plant growth stimulation by a strain of Pseudomonas fluorescens
bacterium.
PQQ as a prosthetic group on Glucose Dehydrogenase has been utilized at the anode in an enzyme based fuel cell.
PQQ is especially effective in neutralizing superoxide and hydroxyl radicals, two prominent causes of mitochondrial dysfunction.
According to a University of California at Davis study, “PQQ is 30 to 5,000 times more efficient in sustaining redox cycling (mitochondrial energy production) . . . than other common [antioxidant compounds], e.g. Ascorbic Acid (Vitamin C).”
Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis. The implications of this revelation for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise, strict caloric restriction, and certain medications such as thiazolidinediones and the diabetes drug metformin.
PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 gene, an early step in the onset of Parkinson’s disease.
PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke. Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, producing a significant proportion of subsequent long-term neurological damage. PQQ suppresses RNS in experimentally induced strokes, and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.
In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area. These observations have been extended in vivo by showing that PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke and brain hypoxia.
PQQ interacts beneficially with the brain’s neurotransmitter systems. It protects neurons by modifying the N-Methyl-D-aspartate (NMDA) receptor site and mediating excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.
PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury(a suspected factor in the development of Alzheimer’s disease) and oxidopamine (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons).
PQQ prevents development of alpha-synuclein, a protein associated with Parkinson’s disease. PQQ also protects nerve cells from the oxidizing ravages of the amyloid-beta protein linked with Alzheimer’s disease, and works preventatively to block new amyloid beta molecular structures from forming before they can cause any damage.
In a double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests.
Interestingly, the results of the study also suggest a synergistic relationship between PQQ and the nutrient coenzyme Q10 (CoQ10), which further amplified performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results demonstrated that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients.
Researches at the University of California at San Francisco investigated this potential, comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment. Independently, both treatments reduced the size of the damaged damaged areas’ and protected against heart muscle dysfunction. When given together, the left ventricle’s pumping pressure was enhanced. The combination of PQQ with metoprolol also increased mitochondrial energy-producing functions—but the effect was modest compared with PQQ alone. Only PQQ favorably reduced lipid peroxidation. These results led the researches to conclude that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.” ]
Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function.
Animal studies have demonstrated PQQ's support of healthy mitochondrial function with human equivalent dose (H.E.D.) as low as 1.44 milligrams per day, the majority of actual human studies have used higher doses of 10-20mg or more. Consequently, nearly all PQQ supplements sold in the United States range from 10–20 mg.
Nicotinamide
Nicotinamide, also known as niacinamide and nicotinic acid amide, is the amide of nicotinic acid . Nicotinamide is a water-soluble vitamin and is part of the vitamin B group...
and flavin in bacteria (although they hypothesised that it was naphthoquinone
Naphthoquinone
Naphthoquinone is a class of natural phenols based on the C6-C4 skeleton.1,4-Naphthoquinone can be viewed as derivatives of naphthalene through the replacement of two hydrogen atoms by two ketone groups....
). Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase
Alcohol dehydrogenase
Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide...
and named it methoxatin. In 1979, Salisbury and colleagues as well as Duine and colleagues extracted this prosthetic group from methanol dehydrogenase
Methanol dehydrogenase
In enzymology, a methanol dehydrogenase is an enzyme that catalyses the chemical reaction:How the electrons are captured and transported depends upon the kind of methanol dehydrogenase and there are two main types...
of methylotroph
Methylotroph
Methylotrophs are a diverse group of microorganisms that can use reduced one-carbon compounds, such as methanol or methane, as the carbon source for their growth; and multi-carbon compounds that contain no carbon bonds, such as dimethyl ether and dimethylamine...
s and identified its molecular structure. Adachi and colleagues identified that PQQ was also found in Acetobacter
Acetobacter
Acetobacter is a genus of acetic acid bacteria characterized by the ability to convert ethanol to acetic acid in the presence of oxygen. There are several species within this genus, and there are other bacteria capable of forming acetic acid under various conditions; but all of the Acetobacter are...
.
These enzymes containing PQQ are called quinoproteins. Glucose dehydrogenase
Quinoprotein glucose dehydrogenase
In enzymology, a quinoprotein glucose dehydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are D-glucose and ubiquinone, whereas its two products are D-glucono-1,5-lactone and ubiquinol....
, one of the quinoproteins, is used as a glucose sensor. Subsequently, PQQ was found to stimulate growth in bacteria. In addition, antioxidant and neuro-protective effects were also found.
In 1989, Rucker and colleagues reported that mice deprived of PQQ showed various abnormalities, and it was suggested that PQQ may also have an important nutritional role in other mammals. In 2003, it was reported that aminoadipate semialdehyde dehydrogenase
L-aminoadipate-semialdehyde dehydrogenase
In enzymology, a L-aminoadipate-semialdehyde dehydrogenase is an enzyme that catalyzes the chemical reactionThe 4 substrates of this enzyme are L-2-aminoadipate 6-semialdehyde, NAD+, NADP+, and H2O, whereas its 4 products are L-2-aminoadipate, NADH, NADPH, and H+.This enzyme belongs to the family...
(AASDH) might also use PQQ as a cofactor, suggesting a possibility that PQQ is a vitamin in mammals. Rucker and colleagues concluded that insufficient information is available so far to state that PQQ is a vitamin for mammals, although PQQ may be an important biological factor.
It was recently shown that PQQ may stimulate growth of plants (cucumbers and tomatoes) in hydroponic culture and may be the causative factor in plant growth stimulation by a strain of Pseudomonas fluorescens
Pseudomonas fluorescens
Pseudomonas fluorescens is a common Gram-negative, rod-shaped bacterium. It belongs to the Pseudomonas genus; 16S rRNA analysis has placed P. fluorescens in the P. fluorescens group within the genus, to which it lends its name....
bacterium.
PQQ as a prosthetic group on Glucose Dehydrogenase has been utilized at the anode in an enzyme based fuel cell.
Supplementation Benefits
PQQ is taken as a dietary supplement to support mitochondrial health and cellular energy production, and to protect the body from oxidative stress. Most notably, PQQ stimulates the spontaneous growth of new mitochondria in aging cells, and activates genes that govern mitochondrial reproduction, protection, and repair.Antioxidant Capacity and Role in Mitochondrial Health
Mitochondria are the primary engines of almost all bioenergy production in the human body and are among the most vulnerable physiological structures to destruction from oxidative damage. Scientists now recognize mitochondrial dysfunction as a key biomarker of aging. Relative to cellular DNA, mitochondrial DNA possesses few defenses against free radical damage, and is dependent upon antioxidants for protection. PQQ’s powerful free radical–scavenging capacity provides the mitochondria with superior antioxidant protection due to its high molecular stability and the role it plays in energy transfer directly within the mitochondria. Unlike other antioxidants, the exceptional molecular stability of PQQ allows it to carry out thousands of electron transfers without undergoing molecular breakdownPQQ is especially effective in neutralizing superoxide and hydroxyl radicals, two prominent causes of mitochondrial dysfunction.
According to a University of California at Davis study, “PQQ is 30 to 5,000 times more efficient in sustaining redox cycling (mitochondrial energy production) . . . than other common [antioxidant compounds], e.g. Ascorbic Acid (Vitamin C).”
Mitochondrial Biogenesis
In 2010, researchers at the University of California at Davis released a peer-reviewed publication showing that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development, and function.Most significantly, the study demonstrated that PQQ not only protects mitochondria from oxidative stress—it promotes the spontaneous generation of new mitochondria within aging cells, a process known as mitochondrial biogenesis. The implications of this revelation for human health and longevity are significant because the only other known methods proven to stimulate mitochondiral biogenesis in aging humans are intense aerobic exercise, strict caloric restriction, and certain medications such as thiazolidinediones and the diabetes drug metformin.
Activation of Signaling Molecules
The team of researchers at the University of California analyzed PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria and found that there are three signaling molecules activated by PQQ that cause cells to undergo spontaneous mitochondrial biogenesis:- PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gammaPeroxisome proliferator-activated receptor gammaPeroxisome proliferator-activated receptor gamma , also known as the glitazone receptor, or NR1C3 is a type II nuclear receptor that in humans is encoded by the PPARG gene.Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 and...
coactivator 1-alpha), a “master regulator” that mobilizes cells’ response to various external triggers. It directly stimulates genes that enhance mitochondrial and cellular respiration, growth, and reproduction. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.
- PQQ triggers the CREBCREBCREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....
signaling protein (cAMP-response element-binding protein), which plays a pivotal role in embryonic development and growth. It also beneficially interacts with histoneHistoneIn biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s, molecular compounds shown to protect and repair cellular DNA. CREB also stimulates the growth of new mitochondria.
- PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is intrinsically involved in cell function and survival, has been shown to prevent cell death by combating intensive antioxidant stress,and is of particular importance to brain health and function. DJ-1 damage and mutation have been conclusively linked to the onset of Parkinson’s disease and other neurological disorders.
Neuroprotection
PQQ is a potent neuroprotective nutrient that has been shown to protect memory and cognition in both aging animals and humans. It has been shown to reverse cognitive impairment caused by chronic oxidative stress in pre-clinical models and improve performance on memory tests. PQQ supplementation stimulates the production and release of nerve growth factor in cells that support neurons in the brain, a possible explanation for the marked improvement of memory function it produces in aging humans and rats.PQQ has also been shown to safeguard against the self-oxidation of the DJ-1 gene, an early step in the onset of Parkinson’s disease.
PQQ protects brain cells against oxidative damage following ischemia-reperfusion injury—the inflammation and oxidative damage that result from the sudden return of blood and nutrients to tissues deprived of them by stroke. Reactive nitrogen species (RNS) arise spontaneously following stroke and spinal cord injuries and impose severe stresses on damaged neurons, producing a significant proportion of subsequent long-term neurological damage. PQQ suppresses RNS in experimentally induced strokes, and provides additional protection following spinal cord injury by blocking inducible nitric oxide synthase (iNOS), a major source of RNS.
In animal models, administration of PQQ immediately prior to induction of stroke significantly reduces the size of the damaged brain area. These observations have been extended in vivo by showing that PQQ protects against the likelihood of severe stroke in an experimental animal model for stroke and brain hypoxia.
PQQ interacts beneficially with the brain’s neurotransmitter systems. It protects neurons by modifying the N-Methyl-D-aspartate (NMDA) receptor site and mediating excitotoxicity—the damaging consequence of long-term overstimulation of neurons that is associated with many neurodegenerative diseases and seizures.
PQQ also protects the brain against neurotoxicity induced by other powerful toxins, including mercury(a suspected factor in the development of Alzheimer’s disease) and oxidopamine (a potent neurotoxin used by scientists to induce Parkinsonism in laboratory animals by destroying dopaminergic and noradrenergic neurons).
PQQ prevents development of alpha-synuclein, a protein associated with Parkinson’s disease. PQQ also protects nerve cells from the oxidizing ravages of the amyloid-beta protein linked with Alzheimer’s disease, and works preventatively to block new amyloid beta molecular structures from forming before they can cause any damage.
Cognition
PQQ has been shown to promote memory, attention, and cognition in animals and humans.In a double-blind, placebo-controlled clinical trial conducted in Japan in 2007, supplementation with 20 mg per day of PQQ resulted in improvements on tests of higher cognitive function in a group of 71 middle-aged and elderly people aged between 40-70, who outperformed the placebo group by more than twofold in their standardized memory tests.
Interestingly, the results of the study also suggest a synergistic relationship between PQQ and the nutrient coenzyme Q10 (CoQ10), which further amplified performance on standardized memory tests when subjects also took 300 mg per day of CoQ10. No adverse effects were linked to the supplementation, and the results demonstrated that PQQ, especially when combined with CoQ10, can be used to improve mental status and quality of life in older patients, and help slow or prevent age-related cognitive decline in middle-age patients.
Cardioprotection
Damage from a heart attack, like a stroke, is inflicted via ischemia-reperfusion injury. Supplemental PQQ reduces the size of damaged areas in animal models of acute heart attack (myocardial infarction). Significantly, this occurs whether the supplement is given before or after the ischemic event itself, suggesting that supplementation within the first hours of medical response may offer profound benefits to heart attack victims.Researches at the University of California at San Francisco investigated this potential, comparing PQQ with the beta blocker metoprolol—a standard post-MI clinical treatment. Independently, both treatments reduced the size of the damaged damaged areas’ and protected against heart muscle dysfunction. When given together, the left ventricle’s pumping pressure was enhanced. The combination of PQQ with metoprolol also increased mitochondrial energy-producing functions—but the effect was modest compared with PQQ alone. Only PQQ favorably reduced lipid peroxidation. These results led the researches to conclude that “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.” ]
Subsequent research has also demonstrated that PQQ helps heart muscle cells resist acute oxidative stress by preserving and enhancing mitochondrial function.
Supplement Dosage
Despite its classification as an essential nutrient, no recommended daily intake of PQQ has been established.Animal studies have demonstrated PQQ's support of healthy mitochondrial function with human equivalent dose (H.E.D.) as low as 1.44 milligrams per day, the majority of actual human studies have used higher doses of 10-20mg or more. Consequently, nearly all PQQ supplements sold in the United States range from 10–20 mg.