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|
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 [Bauer04a]. 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 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, Zhang10a]. 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].
Bauer04a: 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
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
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
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
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
Zhang10a: 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
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
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
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