Pyrroloquinoline quinone

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Pyrroloquinoline quinone
Pyrroloquinoline quinone.svg
Names
Systematic IUPAC name
4,5-Dioxo-4,5-dihydro-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid
Identifiers
3D model (JSmol)
3596812
ChEBI
ChEMBL
ChemSpider
DrugBank
EC Number
  • 839-691-6
56633
KEGG
MeSH PQQ+Cofactor
PubChem CID
UNII
  • InChI=1S/C14H6N2O8/c17-10-4-2-6(14(23)24)15-8(4)7-3(12(19)20)1-5(13(21)22)16-9(7)11(10)18/h1-2,15H,(H,19,20)(H,21,22)(H,23,24) Yes check.svgY
    Key: MMXZSJMASHPLLR-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C14H6N2O8/c17-10-4-2-6(14(23)24)15-8(4)7-3(12(19)20)1-5(13(21)22)16-9(7)11(10)18/h1-2,15H,(H,19,20)(H,21,22)(H,23,24)
    Key: MMXZSJMASHPLLR-UHFFFAOYAP
  • c1c2c([nH]c1C(=O)O)-c3c(cc(nc3C(=O)C2=O)C(=O)O)C(=O)O
Properties
C14H6N2O8
Molar mass 330.208 g·mol−1
Density 1.963 g/cm3
Hazards
Flash point 569.8 °C (1,057.6 °F; 842.9 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Pyrroloquinoline quinone (PQQ), also called methoxatin, is a redox cofactor and antioxidant. [1]

Quinoprotein glucose dehydrogenase is used as a glucose sensor in bacteria. PQQ stimulates growth in bacteria. [2]

History

It was discovered by J. G. Hauge as the third redox cofactor after nicotinamide and flavin in bacteria (although he hypothesised that it was naphthoquinone). [3] Anthony and Zatman also found the unknown redox cofactor in alcohol dehydrogenase. In 1979, Salisbury and colleagues [4] as well as Duine and colleagues [5] extracted this prosthetic group from methanol dehydrogenase of methylotrophs and identified its molecular structure. Adachi and colleagues discovered that PQQ was also found in Acetobacter . [6]

Biosynthesis

A novel aspect of PQQ is its biosynthesis in bacteria from a ribosomally translated precursor peptide, PqqA (UniProt P27532 ). [7] A glutamic acid and a tyrosine in PqqA are cross-linked by the radical SAM enzyme PqqE ( P07782 ) with the help of PqqD ( P07781 ) in the first step of PqqA modification. [8] A protease then liberates the Glu-Tyr molecule from the peptide backbone. PqqB ( P07779 ) oxidizes the 2 and 3 positions on the tyrosine ring, forming a quinone which quickly becomes AHQQ, finishing the pyridine ring. PqqC ( P07780 ) then forms the final pyrrole ring. [9]

Efforts to understand PQQ biosynthesis have contributed to broad interest in radical SAM enzymes and their ability to modify proteins, and an analogous radical SAM enzyme-dependent pathway has since been found that produces the putative electron carrier mycofactocin, using a valine and a tyrosine from the precursor peptide, MftA ( P9WJ81 ). [8]

Role in proteins

Quinoproteins generally embed the cofactor in a unique, six-bladed [10] beta-barrel structure. Some examples also have a heme c prosthetic group and are termed quinohemoproteins. [11] Although quinoproteins are mostly found in bacteria, a Coprinopsis cinerea (fungus) pyranose dehydrogenase has been shown to use PQQ in its crystal structure. [10]

PQQ also appears to be essential in some other eukaryotic proteins, albeit not as the direct electron carrier. The aforementioned mammalian lactate dehydrogenase requires PQQ to run but uses NADH as the direct redox cofactor. It seems to speed up the reaction by catalyzing the oxidation of NADH via redox cycling. [12]

Controversy regarding role as vitamin

The scientific journal Nature published the 2003 paper by Kasahara and Kato that essentially stated that PQQ was a new vitamin and in 2005, an article by Anthony and Felton that stated that the 2003 Kasahara and Kato paper drew incorrect and unsubstantiated conclusions. [13] An article by Bruce Ames in The Proceedings of the National Academy of Sciences in 2018 identified pyrroloquinoline quinone as a "longevity vitamin" not essential for immediate survival, but necessary for long-term health. [14]

See also

Related Research Articles

<span class="mw-page-title-main">Methionine</span> Sulfur-containing amino acid

Methionine is an essential amino acid in humans.

<span class="mw-page-title-main">Flavin group</span> Group of chemical compounds

Flavins refers generally to the class of organic compounds containing the tricyclic heterocycle isoalloxazine or its isomer alloxazine, and derivatives thereof. The biochemical source of flavin is the yellow B vitamin riboflavin. The flavin moiety is often attached with an adenosine diphosphate to form flavin adenine dinucleotide (FAD), and, in other circumstances, is found as flavin mononucleotide, a phosphorylated form of riboflavin. It is in one or the other of these forms that flavin is present as a prosthetic group in flavoproteins. Despite the similar names, flavins are chemically and biologically distinct from the flavanoids, and the flavonols.

<span class="mw-page-title-main">Succinate dehydrogenase</span> Enzyme

Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. Histochemical analysis showing high succinate dehydrogenase in muscle demonstrates high mitochondrial content and high oxidative potential.

<span class="mw-page-title-main">Flavin adenine dinucleotide</span> Redox-active coenzyme

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex.

<span class="mw-page-title-main">Vitamin K epoxide reductase</span> Class of enzymes

Vitamin K epoxide reductase (VKOR) is an enzyme that reduces vitamin K after it has been oxidised in the carboxylation of glutamic acid residues in blood coagulation enzymes. VKOR is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea. In some plant and bacterial homologues, the VKOR domain is fused with domains of the thioredoxin family of oxidoreductases.

<span class="mw-page-title-main">Methanol dehydrogenase</span>

In enzymology, a methanol dehydrogenase (MDH) is an enzyme that catalyzes the chemical reaction:

In enzymology, a pyrroloquinoline-quinone synthase (EC 1.3.3.11) is an enzyme that catalyzes the chemical reaction

In enzymology, an alcohol dehydrogenase (acceptor) (EC 1.1.99.8) is an enzyme that catalyzes the chemical reaction

In enzymology, a choline dehydrogenase is an enzyme that catalyzes the chemical reaction

In enzymology, a quinoprotein glucose dehydrogenase is an enzyme that catalyzes the chemical reaction

In enzymology, an aldehyde dehydrogenase (pyrroloquinoline-quinone) (EC 1.2.99.3) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Amine oxidase (copper-containing)</span>

Amine oxidase (copper-containing) (AOC) (EC 1.4.3.21 and EC 1.4.3.22; formerly EC 1.4.3.6) is a family of amine oxidase enzymes which includes both primary-amine oxidase and diamine oxidase; these enzymes catalyze the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. They act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor:

Radical SAMenzymes is a superfamily of enzymes that use a [4Fe-4S]+ cluster to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical (5'-dAdo), as a critical intermediate. These enzymes utilize this radical intermediate to perform diverse transformations, often to functionalize unactivated C-H bonds. Radical SAM enzymes are involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily, and have a cysteine-rich motif that matches or resembles CxxxCxxC. Radical SAM enzymes comprise the largest superfamily of metal-containing enzymes.

<span class="mw-page-title-main">Methanol dehydrogenase (cytochrome c)</span>

Methanol dehydrogenase (cytochrome c) (EC 1.1.2.7, methanol dehydrogenase, MDH) is an enzyme with systematic name methanol:cytochrome c oxidoreductase. This enzyme catalyses the following chemical reaction

Alcohol dehydrogenase (cytochrome c) (EC 1.1.2.8, type I quinoprotein alcohol dehydrogenase, quinoprotein ethanol dehydrogenase) is an enzyme with systematic name alcohol:cytochrome c oxidoreductase. This enzyme catalyses the following chemical reaction

Alcohol dehydrogenase (quinone) (EC 1.1.5.5, type III ADH, membrane associated quinohaemoprotein alcohol dehydrogenase) is an enzyme with systematic name alcohol:quinone oxidoreductase. This enzyme catalyses the following chemical reaction

Quinate dehydrogenase (quinone) (EC 1.1.5.8, NAD(P)+-independent quinate dehydrogenase, quinate:pyrroloquinoline-quinone 5-oxidoreductase) is an enzyme with systematic name quinate:quinol 3-oxidoreductase. This enzyme catalyses the following chemical reaction

Alcohol dehydrogenase (azurin) (EC 1.1.9.1, type II quinoprotein alcohol dehydrogenase, quinohaemoprotein ethanol dehydrogenase, QHEDH, ADHIIB) is an enzyme with systematic name alcohol:azurin oxidoreductase. This enzyme catalyses the following chemical reaction

Soluble quinoprotein glucose dehydrogenase is an enzyme with systematic name D-glucose:acceptor oxidoreductase. This enzyme catalyses the following chemical reaction

Mycofactocin (MFT) is a family of small molecules derived from a peptide of the type known as RiPP (ribosomally synthesized and post-translationally modified peptides), naturally occurring in many types of Mycobacterium. It was discovered in a bioinformatics study in 2011. All mycofactocins share a precursor in the form of premycofactocin (PMFT); they differ by the cellulose tail added. Being redox active, both PMFT and MFT have an oxidized dione (mycofactocinone) form and a reduced diol (mycofactocinol) form, respectively termed PMFTH2 and MFTH2.

References

  1. ↑ Wen H, He Y, Zhang K, Yang X, Hao D, Jiang Y, He B. Mini-review: Functions and Action Mechanisms of PQQ in Osteoporosis and Neuro Injury. Curr Stem Cell Res Ther. 2020;15(1):32-36. doi : 10.2174/1574888X14666181210165539 PMID   30526470
  2. ↑ Ameyama M, Matsushita K, Shinagawa E, Hayashi M, Adachi O (1988). "Pyrroloquinoline quinone: excretion by methylotrophs and growth stimulation for microorganisms". BioFactors. 1 (1): 51–3. PMID   2855583.
  3. ↑ Hauge JG (1964). "Glucose dehydrogenase of bacterium anitratum: an enzyme with a novel prosthetic group". J Biol Chem. 239 (11): 3630–9. doi: 10.1016/S0021-9258(18)91183-X . PMID   14257587.
  4. ↑ Salisbury SA, Forrest HS, Cruse WB, Kennard O (1979). "A novel coenzyme from bacterial primary alcohol dehydrogenases". Nature. 280 (5725): 843–4. Bibcode:1979Natur.280..843S. doi:10.1038/280843a0. PMID   471057. S2CID   3094647.
  5. ↑ Westerling J, Frank J, Duine JA (1979). "The prosthetic group of methanol dehydrogenase from Hyphomicrobium X: electron spin resonance evidence for a quinone structure". Biochem Biophys Res Commun. 87 (3): 719–24. doi:10.1016/0006-291X(79)92018-7. PMID   222269.
  6. ↑ Ameyama M, Matsushita K, Ohno Y, Shinagawa E, Adachi O (1981). "Existence of a novel prosthetic group, PQQ, in membrane-bound, electron transport chain-linked, primary dehydrogenases of oxidative bacteria". FEBS Lett. 130 (2): 179–83. doi: 10.1016/0014-5793(81)81114-3 . PMID   6793395.
  7. ↑ Goosen N, Huinen RG, van de Putte P (1992). "A 24-amino-acid polypeptide is essential for the biosynthesis of the coenzyme pyrrolo-quinoline-quinone". J Bacteriol. 174 (4): 1426–7. doi:10.1128/jb.174.4.1426-1427.1992. PMC   206443 . PMID   1310505.
  8. 1 2 Haft DH (2011). "Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners". BMC Genomics. 12: 21. doi: 10.1186/1471-2164-12-21 . PMC   3023750 . PMID   21223593.
  9. ↑ Zhu, W; Klinman, JP (December 2020). "Biogenesis of the peptide-derived redox cofactor pyrroloquinoline quinone". Current Opinion in Chemical Biology. 59: 93–103. doi:10.1016/j.cbpa.2020.05.001. PMC   7736144 . PMID   32731194.
  10. 1 2 Takeda, K; Ishida, T; Yoshida, M; Samejima, M; Ohno, H; Igarashi, K; Nakamura, N (15 December 2019). "Crystal Structure of the Catalytic and Cytochrome b Domains in a Eukaryotic Pyrroloquinoline Quinone-Dependent Dehydrogenase". Applied and Environmental Microbiology. 85 (24). Bibcode:2019ApEnM..85E1692T. doi: 10.1128/AEM.01692-19 . PMC   6881789 . PMID   31604769.
  11. ↑ Matsushita, K; Toyama, H; Yamada, M; Adachi, O (January 2002). "Quinoproteins: structure, function, and biotechnological applications". Applied Microbiology and Biotechnology. 58 (1): 13–22. doi:10.1007/s00253-001-0851-1. PMID   11831471. S2CID   12469203.
  12. ↑ Akagawa, M; Minematsu, K; Shibata, T; Kondo, T; Ishii, T; Uchida, K (27 May 2016). "Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein". Scientific Reports. 6: 26723. Bibcode:2016NatSR...626723A. doi:10.1038/srep26723. PMC   4882622 . PMID   27230956.
  13. ↑ Felton LM, Anthony C (2005). "Biochemistry: role of PQQ as a mammalian enzyme cofactor?". Nature. 433 (7025): E10, discussion E11–2. Bibcode:2005Natur.433E..10F. doi: 10.1038/nature03322 . PMID   15689995. S2CID   4370935.
  14. ↑ Ames, Bruce (15 October 2018). "Prolonging healthy aging: Longevity vitamins and proteins". Proceedings of the National Academy of Sciences of the United States of America. 115 (43): 10836–10844. Bibcode:2018PNAS..11510836A. doi: 10.1073/pnas.1809045115 . PMC   6205492 . PMID   30322941.
  15. ↑ "L-aminoadipate-semialdehyde dehydrogenase (Homo sapiens)". BRENDA. Technische Universität Braunschweig. July 2015. Retrieved 18 July 2015.
  16. ↑ "Pyrroloquinoline quinone (HMDB13636)". Human Metabolome Database. University of Alberta. Retrieved 19 July 2015, citing:
    • PMID   2558842: "Enzymes containing PQQ are called quinoproteins. PQQ and quinoproteins play a role in the redox metabolism and structural integrity of cells and tissues."
    • PMID   12712191: "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."
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