Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Folate Biosynthesis → Folate Transformations|
Pathway Summary from MetaCyc:
The formation of the formyl and methyl derivatives of tetrahydrofolate (vitamin B9) directly involved in or representing sidesteps of the biosynthesis of this vital cofactors [Cossins97] [Hanson00] is displayed in this pathway. Folates are involved in a wide range of key metabolic functions in plants [Hanson02] [Jabrin03] mediating fluxes through C1-pathways with a high demand for methylated compounds such as secondary metabolites [Hanson01].
Plants prefer the polyglutamylated forms of folates (compare folate polyglutamylation, glutamate removal from folates) since the turnover rate of those compounds is markedly increased [Cossins97] [Scott00] and meets the high demands for folates as observed in plants [Hanson02]. In addition the conjugated forms of folate facilitate the retention of the vitamin within the cell and its subcellular compartments [Appling91]. The plant enzymes involved in this pathway, although essentially catalyzing the same steps, have been found to differ in many regards from their bacterial counterparts [Cossins97] [Basset04a] [Basset04].
Folates are tripartite molecules and are made up of pterin, p-aminobenzoate (pPABA) and glutamate moieties. The one-carbon units are either attached to the N-5 of the pterin moietie, to the N-10 of the pPAPA moiety or are brigded in between those two (e.g. 5,10-methenyl or methylene-THF) [Basset05]. The different forms of folates are jointly connected and easily convertible into each other through a tight network of reactions ( folate transformations I). Most of the enzymes have been identified in plants but some of them such as the formyltetrahydrofolate deformylase, presumably involved in the mutual conversion of tetrahydrofolate and its 10-formyl derivative remain to be demonstrated.
Among the many folates N5-formyl-tetrahydrofolate is the most enigmatic compound involved in the folate biosynthesis. N5-formyl-tetrahydrofolate is the only folate derivative that does not serve as a cofactor in the C1-metabolism, but it is the most frequent and stable form of folates found in plants [Stover93]. Moreover, N5-formyl-tetrahydrofolate is known to inhibit most of the folate dependent enzymes at physiological concentrations. The biological role of this compound is still poorly understood but it has been discussed as factor involved in the regulation of essential biosynthetic steps such as the formation of serine during photorespiration [Goyer05, Roje02].
The complete set of folate enzymes is only present in mitochondria. However, the recent discovery that folylpolyglutamate synthases are present in cytosol, mitochondria and plastids with each of them encoded by a different gene in Arabidopsis thaliana [Ravanel01] points to the fact that at least parts of the pathway can be carried out independently in those compartments. Interestingly, the enzyme hydrolyzing the polyglutamylated folates (γ-glutamyl hydrolase) has been found to be an extracellular enzyme in plants [Huangpu96]. Consequently, the transport and exact conversion of folates and their derivatives within the different cell compartments and their regulation pattern remains to be clarified before successfully attempting the endeavor to genetically engineer this pathway.
Variants: folate transformations I
Pathway Evidence Glyph:
This organism is not in the expected taxonomic range for this pathway.
Key to pathway glyph edge colors:
An enzyme catalyzing this reaction is present in this organism
No enzyme catalyzing this reaction has been identified in this organism
The reaction is unique to this pathway in MetaCyc
Basset04: Basset GJ, Ravanel S, Quinlivan EP, White R, Giovannoni JJ, Rebeille F, Nichols BP, Shinozaki K, Seki M, Gregory JF, Hanson AD (2004). "Folate synthesis in plants: the last step of the p-aminobenzoate branch is catalyzed by a plastidial aminodeoxychorismate lyase." Plant J 40(4);453-61. PMID: 15500462
Basset04a: Basset GJ, Quinlivan EP, Ravanel S, Rebeille F, Nichols BP, Shinozaki K, Seki M, Adams-Phillips LC, Giovannoni JJ, Gregory JF, Hanson AD (2004). "Folate synthesis in plants: the p-aminobenzoate branch is initiated by a bifunctional PabA-PabB protein that is targeted to plastids." Proc Natl Acad Sci U S A 101(6);1496-501. PMID: 14745019
Goyer05: Goyer A, Collakova E, Diaz de la Garza R, Quinlivan EP, Williamson J, Gregory JF, Shachar-Hill Y, Hanson AD (2005). "5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves." J Biol Chem 280(28);26137-42. PMID: 15888445
Huangpu96: Huangpu J, Pak JH, Graham MC, Rickle SA, Graham JS (1996). "Purification and molecular analysis of an extracellular gamma-glutamyl hydrolase present in young tissues of the soybean plant." Biochem Biophys Res Commun 228(1);1-6. PMID: 8912628
Jabrin03: Jabrin S, Ravanel S, Gambonnet B, Douce R, Rebeille F (2003). "One-carbon metabolism in plants. Regulation of tetrahydrofolate synthesis during germination and seedling development." Plant Physiol 131(3);1431-9. PMID: 12644692
Ravanel01: Ravanel S, Cherest H, Jabrin S, Grunwald D, Surdin-Kerjan Y, Douce R, Rebeille F (2001). "Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana." Proc Natl Acad Sci U S A 98(26);15360-5. PMID: 11752472
Roje02: Roje S, Janave MT, Ziemak MJ, Hanson AD (2002). "Cloning and characterization of mitochondrial 5-formyltetrahydrofolate cycloligase from higher plants." J Biol Chem 277(45);42748-54. PMID: 12207015
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