A central role for gamma-glutamyl hydrolases in plant folate homeostasis

Akhtar, Tariq A.; Orsomando, Giuseppe; Mehrshahi, Payam; Lara‐Núñez, Aurora; Bennett, Malcolm J.; Gregory, Jesse F.; Hanson, Andrew D.

doi:10.1111/j.1365-313x.2010.04330.x

Cited by 50 publications

(43 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most cellular folates carry a short poly-γ-Glu tail, which is believed to affect their efficacy and stability. The tail can be removed by γ-glutamyl hydrolase (GGH), a vacuolar enzyme who has an important influence on polyglutamyl tail length and hence on folate stability and cellular folate content [19]. Folylpolyglutamate derivatives are central cofactors for many folate-dependent enzymes [20], [21], [22], [23], [24], [25].…”

Section: Introductionmentioning

confidence: 99%

Arabidopsis Plastidial Folylpolyglutamate Synthetase Is Required for Seed Reserve Accumulation and Seedling Establishment in Darkness

Meng

Ling

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Interactions among metabolic pathways are important in plant biology. At present, not much is known about how folate metabolism affects other metabolic pathways in plants. Here we report a T-DNA insertion mutant (atdfb-3) of the plastidial folylpolyglutamate synthetase gene (AtDFB) was defective in seed reserves and skotomorphogenesis. Lower carbon (C) and higher nitrogen (N) content in the mutant seeds than that of the wild type were indicative of an altered C and N partitioning capacity. Higher levels of organic acids and sugars were detected in the mutant seeds compared with the wild type. Further analysis revealed that atdfb-3 seeds contained less total amino acids and individual Asn and Glu as well as NO3 −. These results indicate significant changes in seed storage in the mutant. Defects in hypocotyl elongation were observed in atdfb-3 in darkness under sufficient NO3 − conditions, and further enhanced under NO3 − limited conditions. The strong expression of AtDFB in cotyledons and hypocotyl during early developmental stage was consistent with the mutant sensitivity to limited NO3 − during a narrow developmental window. Exogenous 5-formyl-tetrahydrofolate completely restored the hypocotyl length in atdfb-3 seedlings with NO3 − as the sole N source. Further study demonstrated that folate profiling and N metabolism were perturbed in atdfb-3 etiolated seedlings. The activity of enzymes involved in N reduction and assimilation was altered in atdfb-3. Taken together, these results indicate that AtDFB is required for seed reserves, hypocotyl elongation and N metabolism in darkness, providing novel insights into potential associations of folate metabolism with seed reserve accumulation, N metabolism and hypocotyl development in Arabidopsis.

show abstract

Section: Introductionmentioning

confidence: 99%

Arabidopsis Plastidial Folylpolyglutamate Synthetase Is Required for Seed Reserve Accumulation and Seedling Establishment in Darkness

Meng

Ling

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Similarly, temperature extremes, high light levels, pH excursions, and stress-driven accumulations Table I. of metabolites with which cofactors react all directly accelerate diverse types of spontaneous cofactor damage (Treadwell and Metzler, 1972;Baggott, 2000;Mills et al, 2006;Marbaix et al, 2011). Abiotic stresses can also promote cofactor damage indirectly by altering compartmentation (Akhtar et al, 2010;Mohammadi et al, 2012) by inducing enzymes that break down cofactors (Rapala-Kozik et al, 2008;Higa et al, 2012) and by creating harsh cellular conditions in which enzymes that normally act on other substrates become more promiscuous (Piedrafita et al, 2015) and mistakenly attack cofactors. Figure 1 uses color-coded arrows to show the site and nature of damage reactions that vitamins and cofactors can undergo in physiological conditions, and Table I catalogs the reactions corresponding to the arrows.…”

Section: Chemical and Metabolic Lability: Why Bad Things Happen To Gomentioning

confidence: 99%

Does Abiotic Stress Cause Functional B Vitamin Deficiency in Plants?

et al. 2016

Self Cite

View full text Add to dashboard Cite

B vitamins are the precursors of essential metabolic cofactors but are prone to destruction under stress conditions. It is therefore a priori reasonable that stressed plants suffer B vitamin deficiencies and that certain stress symptoms are metabolic knock-on effects of these deficiencies. Given the logic of these arguments, and the existence of data to support them, it is a shock to realize that the roles of B vitamins in plant abiotic stress have had minimal attention in the literature (100-fold less than hormones) and continue to be overlooked. In this article, we therefore aim to explain the connections among B vitamins, enzyme cofactors, and stress conditions in plants. We first outline the chemistry and biochemistry of B vitamins and explore the concept of vitamin deficiency with the help of information from mammals. We then summarize classical and recent evidence for stress-induced vitamin deficiencies and for plant responses that counter these deficiencies. Lastly, we consider potential implications for agriculture.

show abstract

“…The cellular function of polyglutamylation remains unclear, although work has suggested that it plays a role in the stability, cellular retention, enzyme specificity, and homeostasis of folates (53,54). It is possible that 5-CHO-H 4 PteGlu n serves as a folate reserve that contributes to bacterial survival of folate antagonism.…”

Section: Discussionmentioning

confidence: 99%

Bacterial Conversion of Folinic Acid Is Required for Antifolate Resistance

Ogwang

Nguyen

Sherman

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Antifolates, which are among the first antimicrobial agents invented, inhibit cell growth by creating an intracellular state of folate deficiency. Clinical resistance to antifolates has been mainly attributed to mutations that alter structure or expression of enzymes involved in de novo folate synthesis. We identified a Mycobacterium smegmatis mutant, named FUEL (which stands for folate utilization enzyme for leucovorin), that is hypersusceptible to antifolates. Chemical complementation indicated that FUEL is unable to metabolize folinic acid (also known as leucovorin or 5-formyltetrahydrofolate), whose metabolic function remains unknown. Targeted mutagenesis, genetic complementation, and biochemical studies showed that FUEL lacks 5,10-methenyltetrahydrofolate synthase (MTHFS; also called 5-formyltetrahydrofolate cyclo-ligase; EC 6.3.3.2) activity responsible for the only ATP-dependent, irreversible conversion of folinic acid to 5,10-methenyltetrahydrofolate. In trans expression of active MTHFS proteins from bacteria or human restored both antifolate resistance and folinic acid utilization to FUEL. Absence of MTHFS resulted in marked cellular accumulation of polyglutamylated species of folinic acid. Importantly, MTHFS also affected M. smegmatis utilization of monoglutamylated 5-methyltetrahydrofolate exogenously added to the medium. Likewise, Escherichia coli mutants lacking MTHFS became susceptible to antifolates. These results indicate that folinic acid conversion by MTHFS is required for bacterial intrinsic antifolate resistance and folate homeostatic control. This novel mechanism of antimicrobial antifolate resistance might be targeted to sensitize bacterial pathogens to classical antifolates.

show abstract

A central role for gamma-glutamyl hydrolases in plant folate homeostasis

Cited by 50 publications

References 51 publications

Arabidopsis Plastidial Folylpolyglutamate Synthetase Is Required for Seed Reserve Accumulation and Seedling Establishment in Darkness

Arabidopsis Plastidial Folylpolyglutamate Synthetase Is Required for Seed Reserve Accumulation and Seedling Establishment in Darkness

Does Abiotic Stress Cause Functional B Vitamin Deficiency in Plants?

Bacterial Conversion of Folinic Acid Is Required for Antifolate Resistance

Contact Info

Product

Resources

About