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5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves.
J Biol Chem. 2005 Jul 15; 280(28):26137-42.JB

Abstract

5-Formyltetrahydrofolate (5-CHO-THF) is formed via a second catalytic activity of serine hydroxymethyltransferase (SHMT) and strongly inhibits SHMT and other folate-dependent enzymes in vitro. The only enzyme known to metabolize 5-CHO-THF is 5-CHO-THF cycloligase (5-FCL), which catalyzes its conversion to 5,10-methenyltetrahydrofolate. Because 5-FCL is mitochondrial in plants and mitochondrial SHMT is central to photorespiration, we examined the impact of an insertional mutation in the Arabidopsis 5-FCL gene (At5g13050) under photorespiratory (30 and 370 micromol of CO2 mol(-1)) and non-photorespiratory (3200 micromol of CO2 mol(-1)) conditions. The mutation had only mild visible effects at 370 micromol of CO2 mol(-1), reducing growth rate by approximately 20% and delaying flowering by 1 week. However, the mutation doubled leaf 5-CHO-THF level under all conditions and, under photorespiratory conditions, quadrupled the pool of 10-formyl-/5,10-methenyltetrahydrofolates (which could not be distinguished analytically). At 370 micromol of CO2 mol(-1), the mitochondrial 5-CHO-THF pool was 8-fold larger in the mutant and contained most of the 5-CHO-THF in the leaf. In contrast, the buildup of 10-formyl-/5,10-methenyltetrahydrofolates was extramitochondrial. In photorespiratory conditions, leaf glycine levels were up to 46-fold higher in the mutant than in the wild type. Furthermore, when leaves were supplied with 5-CHO-THF, glycine accumulated in both wild type and mutant. These data establish that 5-CHO-THF can inhibit SHMT in vivo and thereby influence glycine pool size. However, the near-normal growth of the mutant shows that even exceptionally high 5-CHO-THF levels do not much affect fluxes through SHMT or any other folate-dependent reaction, i.e. that 5-CHO-THF is well tolerated in plants.

Authors+Show Affiliations

Horticultural Sciences Department, University of Florida, Gainesville, Florida 32611, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

15888445

Citation

Goyer, Aymeric, et al. "5-Formyltetrahydrofolate Is an Inhibitory but Well Tolerated Metabolite in Arabidopsis Leaves." The Journal of Biological Chemistry, vol. 280, no. 28, 2005, pp. 26137-42.
Goyer A, Collakova E, Díaz de la Garza R, et al. 5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves. J Biol Chem. 2005;280(28):26137-42.
Goyer, A., Collakova, E., Díaz de la Garza, R., Quinlivan, E. P., Williamson, J., Gregory, J. F., Shachar-Hill, Y., & Hanson, A. D. (2005). 5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves. The Journal of Biological Chemistry, 280(28), 26137-42.
Goyer A, et al. 5-Formyltetrahydrofolate Is an Inhibitory but Well Tolerated Metabolite in Arabidopsis Leaves. J Biol Chem. 2005 Jul 15;280(28):26137-42. PubMed PMID: 15888445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves. AU - Goyer,Aymeric, AU - Collakova,Eva, AU - Díaz de la Garza,Rocío, AU - Quinlivan,Eoin P, AU - Williamson,Jerry, AU - Gregory,Jesse F,3rd AU - Shachar-Hill,Yair, AU - Hanson,Andrew D, Y1 - 2005/05/11/ PY - 2005/5/13/pubmed PY - 2005/9/13/medline PY - 2005/5/13/entrez SP - 26137 EP - 42 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 280 IS - 28 N2 - 5-Formyltetrahydrofolate (5-CHO-THF) is formed via a second catalytic activity of serine hydroxymethyltransferase (SHMT) and strongly inhibits SHMT and other folate-dependent enzymes in vitro. The only enzyme known to metabolize 5-CHO-THF is 5-CHO-THF cycloligase (5-FCL), which catalyzes its conversion to 5,10-methenyltetrahydrofolate. Because 5-FCL is mitochondrial in plants and mitochondrial SHMT is central to photorespiration, we examined the impact of an insertional mutation in the Arabidopsis 5-FCL gene (At5g13050) under photorespiratory (30 and 370 micromol of CO2 mol(-1)) and non-photorespiratory (3200 micromol of CO2 mol(-1)) conditions. The mutation had only mild visible effects at 370 micromol of CO2 mol(-1), reducing growth rate by approximately 20% and delaying flowering by 1 week. However, the mutation doubled leaf 5-CHO-THF level under all conditions and, under photorespiratory conditions, quadrupled the pool of 10-formyl-/5,10-methenyltetrahydrofolates (which could not be distinguished analytically). At 370 micromol of CO2 mol(-1), the mitochondrial 5-CHO-THF pool was 8-fold larger in the mutant and contained most of the 5-CHO-THF in the leaf. In contrast, the buildup of 10-formyl-/5,10-methenyltetrahydrofolates was extramitochondrial. In photorespiratory conditions, leaf glycine levels were up to 46-fold higher in the mutant than in the wild type. Furthermore, when leaves were supplied with 5-CHO-THF, glycine accumulated in both wild type and mutant. These data establish that 5-CHO-THF can inhibit SHMT in vivo and thereby influence glycine pool size. However, the near-normal growth of the mutant shows that even exceptionally high 5-CHO-THF levels do not much affect fluxes through SHMT or any other folate-dependent reaction, i.e. that 5-CHO-THF is well tolerated in plants. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15888445/5_Formyltetrahydrofolate_is_an_inhibitory_but_well_tolerated_metabolite_in_Arabidopsis_leaves_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15888445 DB - PRIME DP - Unbound Medicine ER -