Cloning and Characterization of Mitochondrial 5-Formyltetrahydrofolate Cycloligase from Higher Plants

Abstract

5-

Arabidopsis Photorespiratory Serine Hydroxymethyltransferase Activity Requires the Mitochondrial Accumulation of Ferredoxin-Dependent Glutamate Synthase

“…It has been recently established that two 10-FDF oppose the accumulation of 5-CHO-THF, and a double loss-of-function mutant confers a photorespiratory phenotype via inhibition of SHMT and GDC activities, confirming the importance of this inhibitor in vivo (Collakova et al, 2008). 5-CHO-THF is metabolized back to 5,10-CH=THF by 5-formyltetrahydrofolate cycloligase, encoded in Arabidopsis by a single 5-FCL gene (Roje et al, 2002). However, the loss of 5-FCL activity does not dramatically reduce plant growth under photorespiratory conditions, despite the accumulation of 5-CHO-THF (Goyer et al, 2005).…”

5-Formyltetrahydrofolate Is an Inhibitory but Well Tolerated Metabolite in Arabidopsis Leaves

“…In photorespiration, glycine coming from peroxisomes is converted to serine in the mitochondria by the concerted action of the glycine decarboxylase complex (GDC) and SHMT. SHMT also mediates formation of 5-CHO-THF from 5,10-CHϭTHF; the reverse reaction is catalyzed by 5-FCL, which is solely mitochondrial in plants (4). Possible SHMT inhibition by 5-CHO-THF is shown by a dashed line.…”

“…5-CHO-THF is the most stable natural folate and the most enigmatic, for it is the only one that does not serve as a cofactor in one-carbon metabolism. Instead, 5-CHO-THF is a potent inhibitor of SHMT and most other folate-dependent enzymes in vitro (4,5). 5-CHO-THF probably acts as a stable storage form of folate in seeds and fungal spores (5-7), but it is not clear what role, if any, it plays in metabolically active tissues (8).…”

“…Whereas the enzyme is largely if not solely cytosolic in yeast and mammals (2,16,20,21), it is exclusively mitochondrial in plants (4). Taken with the key role of mitochondrial SHMT in photorespiration, with the inhibition of SHMT by 5-CHO-THF, and with the presence of 5-CHO-THF in leaf mitochondria, the location of plant 5-FCL implies (i) that this enzyme governs mitochondrial 5-CHO-THF levels and (ii) that, via its effect on 5-CHO-THF levels, 5-FCL could regulate the in vivo activities of SHMT and other folatelinked mitochondrial enzymes (Fig.…”

Potentiation of Available Antibiotics by Targeting Resistance – An Emerging Trend in Tuberculosis Drug Development

“…Because 5-CHO-H 4 PteGlu is known as the most stable form of reduced folate species in nature, and its presence is increased in plant seeds and fungal spores, it was suggested that it might function as a folate storage form required for these dormant states of life (Kruschwitz et al, 1994, Shin et al, 1975, Stover & Schirch, 1993. In mammals and yeasts, 5-CHO-H 4 PteGlu comprises 3-10% of total folate, whereas its presence may account for up to 50% of total folate in plant mitochondria during photorespiration when the glycine to serine flux is accelerated (Goyer et al, 2005, Roje et al, 2002. In vitro, 5-CHO-H 4 PteGlu is also a potential inhibitor of SHMT and other enzymes of the one-carbon metabolism, thus it may potentially serve to regulate these metabolic reactions (Roje et al, 2002, Stover & Schirch, 1991.…”