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MetaCyc Pathway: pyridoxal 5'-phosphate biosynthesis II

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: vitamin B6 biosynthesis

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Vitamins Biosynthesis Vitamin B6 Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col , Bacillus subtilis , Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea , Bacteria , Fungi , Viridiplantae

Summary:
General Background

Vitamin B6 is a group term for pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM) and their 5'-phosphorylated derivatives pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), which are also referred to as vitamers. Pyridoxal 5'-phosphate (PLP) is the biochemically active form, and is an essential cofactor in all living systems [John95]. It plays an important role in amino acid and carbohydrate metabolism and has recently been implicated in singlet oxygen resistance [Daub00]. Most bacteria, archaebacteria, fungi, and plants synthesize PLP in a single reaction, as described in pyridoxal 5'-phosphate biosynthesis II, although some bacteria, such as Escherichia coli, use a longer, more complex pathway (pyridoxal 5'-phosphate biosynthesis I) [Yang98, Sivaraman03]. Animals do not synthesize this compound, making it an essential nutrient in their diet.

PLP is an essential cofactor of numerous metabolic enzymes, predominantly in amino acid metabolism. It is one of the most versatile cofactors and participates in transamination, decarboxylation, racemization, Cα-Cβ cleavage and α-β elimination reactions. In humans this vitamin has a role in numerous functions ranging from modulation of hormone function to potent antioxidant activity.

About This Pathway

The reaction is catalyzed by the pyridoxal 5'-phosphate synthase complex, a dimeric complex that includes two different subunits [Raschle05]. The glutamine hydrolase subunit (encoded by pdxT) catalyzes the hydrolysis of L-glutamine, producing L-glutamate and ammonia [Bauer04]. The ammonia is not released from the enzyme - instead, it is channeled to the active site of the synthase subunit (pdxS) by a 100Å tunnel.

The synthase subunit (Pdx1, pdxS) condenses the ammonium with D-ribose 5-phosphate and D-glyceraldehyde 3-phosphate in a complex series of reactions and produces pyridoxal 5'-phosphate [Hanes08].

The purified proteins have been used in vitro in a reconstituted system [Burns05], and a detailed model for the enzyme's mechanism has been suggested [Raschle07, Hanes08, Hanes08a, Hanes08b].

The formation of pyridoxal 5'-phosphate in Saccharomyces cerevisiae also happens independent of 1-deoxy-D-xylulose 5-phosphate (DXP). The pyridoxal 5'-phosphate synthase complex consists of two subunits, i.e. pyridoxal 5'-phosphate synthase encoded by SNZ1 catalyzing the final formation of pyridoxal 5'-phosphate and a glutaminase encoded by SNO1 providing the ammonia which is the source for the ring nitrogen. It has been demonstrated that the pyridoxal 5'-phosphate synthase not only catalyzes the final formation of pyridoxal 5'-phosphate but also carries out the isomerization of dihydroxyacetone phosphate to D-glyceraldehyde 3-phosphate and D-ribose 5-phosphate to D-ribulose 5-phosphate, the latter being the preferred substrates for the pyridoxal 5'-phosphate synthase. The enzyme has been crystallized and characterized with regard to structure and reaction sequence [Neuwirth09, Zhang10]. The gene encoding the glutaminase, i.e. SNO1 has been demonstrated to only exhibit glutaminase activity when expressed in complex with SNZ1 [Dong04]. From the 3 members in both the SNZ and SNO gene families only the pair SNZ1/SNO1 have been shown to be co-regulated and involved in vitamin B6 (pyridoxal 5'-phosphate) formation [RodriguezNavarr02, Stolz03, Padilla98].

Variants: pyridoxal 5'-phosphate biosynthesis I , pyridoxal 5'-phosphate salvage I , pyridoxal 5'-phosphate salvage II (plants) , superpathway of pyridoxal 5'-phosphate biosynthesis and salvage

Credits:
Created 15-Mar-2010 by Caspi R , SRI International
Revised 07-Jun-2013 by Foerster H , Boyce Thompson Institute


References

Bauer04: Bauer JA, Bennett EM, Begley TP, Ealick SE (2004). "Three-dimensional structure of YaaE from Bacillus subtilis, a glutaminase implicated in pyridoxal-5'-phosphate biosynthesis." J Biol Chem 279(4);2704-11. PMID: 14585832

Burns05: Burns KE, Xiang Y, Kinsland CL, McLafferty FW, Begley TP (2005). "Reconstitution and biochemical characterization of a new pyridoxal-5'-phosphate biosynthetic pathway." J Am Chem Soc 127(11);3682-3. PMID: 15771487

Daub00: Daub ME, Ehrenshaft M (2000). "THE PHOTOACTIVATED CERCOSPORA TOXIN CERCOSPORIN: Contributions to Plant Disease and Fundamental Biology." Annu Rev Phytopathol 38;461-490. PMID: 11701851

Dong04: Dong YX, Sueda S, Nikawa J, Kondo H (2004). "Characterization of the products of the genes SNO1 and SNZ1 involved in pyridoxine synthesis in Saccharomyces cerevisiae." Eur J Biochem 271(4);745-52. PMID: 14764090

Hanes08: Hanes JW, Burns KE, Hilmey DG, Chatterjee A, Dorrestein PC, Begley TP (2008). "Mechanistic studies on pyridoxal phosphate synthase: the reaction pathway leading to a chromophoric intermediate." J Am Chem Soc 130(10);3043-52. PMID: 18271580

Hanes08a: Hanes JW, Keresztes I, Begley TP (2008). "Trapping of a chromophoric intermediate in the Pdx1-catalyzed biosynthesis of pyridoxal 5'-phosphate." Angew Chem Int Ed Engl 47(11);2102-5. PMID: 18260082

Hanes08b: Hanes JW, Keresztes I, Begley TP (2008). "13C NMR snapshots of the complex reaction coordinate of pyridoxal phosphate synthase." Nat Chem Biol 4(7);425-30. PMID: 18516049

John95: John RA (1995). "Pyridoxal phosphate-dependent enzymes." Biochim Biophys Acta 1248(2);81-96. PMID: 7748903

Neuwirth09: Neuwirth M, Strohmeier M, Windeisen V, Wallner S, Deller S, Rippe K, Sinning I, Macheroux P, Tews I (2009). "X-ray crystal structure of Saccharomyces cerevisiae Pdx1 provides insights into the oligomeric nature of PLP synthases." FEBS Lett 583(13);2179-86. PMID: 19523954

Padilla98: Padilla PA, Fuge EK, Crawford ME, Errett A, Werner-Washburne M (1998). "The highly conserved, coregulated SNO and SNZ gene families in Saccharomyces cerevisiae respond to nutrient limitation." J Bacteriol 180(21);5718-26. PMID: 9791124

Raschle05: Raschle T, Amrhein N, Fitzpatrick TB (2005). "On the two components of pyridoxal 5'-phosphate synthase from Bacillus subtilis." J Biol Chem 280(37);32291-300. PMID: 16030023

Raschle07: Raschle T, Arigoni D, Brunisholz R, Rechsteiner H, Amrhein N, Fitzpatrick TB (2007). "Reaction mechanism of pyridoxal 5'-phosphate synthase. Detection of an enzyme-bound chromophoric intermediate." J Biol Chem 282(9);6098-105. PMID: 17189272

RodriguezNavarr02: Rodriguez-Navarro S, Llorente B, Rodriguez-Manzaneque MT, Ramne A, Uber G, Marchesan D, Dujon B, Herrero E, Sunnerhagen P, Perez-Ortin JE (2002). "Functional analysis of yeast gene families involved in metabolism of vitamins B1 and B6." Yeast 19(14);1261-76. PMID: 12271461

Sivaraman03: Sivaraman J, Li Y, Banks J, Cane DE, Matte A, Cygler M (2003). "Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway." J Biol Chem 278(44);43682-90. PMID: 12896974

Stolz03: Stolz J, Vielreicher M (2003). "Tpn1p, the plasma membrane vitamin B6 transporter of Saccharomyces cerevisiae." J Biol Chem 278(21);18990-6. PMID: 12649274

TambascoStudart05: Tambasco-Studart M, Titiz O, Raschle T, Forster G, Amrhein N, Fitzpatrick TB (2005). "Vitamin B6 biosynthesis in higher plants." Proc Natl Acad Sci U S A 102(38);13687-92. PMID: 16157873

Yang98: Yang Y, Zhao G, Man TK, Winkler ME (1998). "Involvement of the gapA- and epd (gapB)-encoded dehydrogenases in pyridoxal 5'-phosphate coenzyme biosynthesis in Escherichia coli K-12." J Bacteriol 1998;180(16);4294-9. PMID: 9696782

Zhang10: Zhang X, Teng YB, Liu JP, He YX, Zhou K, Chen Y, Zhou CZ (2010). "Structural insights into the catalytic mechanism of the yeast pyridoxal 5-phosphate synthase Snz1." Biochem J 432(3);445-50. PMID: 20919991

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Belitsky04: Belitsky BR (2004). "Physical and enzymological interaction of Bacillus subtilis proteins required for de novo pyridoxal 5'-phosphate biosynthesis." J Bacteriol 186(4);1191-6. PMID: 14762015

Fitzpatrick07: Fitzpatrick TB, Amrhein N, Kappes B, Macheroux P, Tews I, Raschle T (2007). "Two independent routes of de novo vitamin B6 biosynthesis: not that different after all." Biochem J 407(1);1-13. PMID: 17822383

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Mooney10: Mooney S, Hellmann H (2010). "Vitamin B6: Killing two birds with one stone?." Phytochemistry 71(5-6);495-501. PMID: 20089286

TambascoStudart07: Tambasco-Studart M, Tews I, Amrhein N, Fitzpatrick TB (2007). "Functional analysis of PDX2 from Arabidopsis, a glutaminase involved in vitamin B6 biosynthesis." Plant Physiol 144(2);915-25. PMID: 17468224


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, biocyc11.