Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce oxidized pterins.
Dihydropterins are intermediates of folate synthesis and products of folate breakdown that are readily oxidized to their aromatic forms. In trypanosomatid parasites, reduction of such oxidized pterins is crucial for pterin and folate salvage. We therefore sought evidence for this reaction in plants. Three lines of evidence indicated its absence. First, when pterin-6-aldehyde or 6-hydroxymethylpterin was supplied to Arabidopsis (Arabidopsis thaliana), pea (Pisum sativum), or tomato (Lycopersicon esculentum) tissues, no reduction of the pterin ring was seen after 15 h, although reduction and oxidation of the side chain of pterin-6-aldehyde were readily detected. Second, no label was incorporated into folates when 6-[(3)H]hydroxymethylpterin was fed to cultured Arabidopsis plantlets for 7 d, whereas [(3)H]folate synthesis from p-[(3)H]aminobenzoate was extensive. Third, no NAD(P)H-dependent pterin ring reduction was found in tissue extracts. Genetic evidence showed a similar situation in Escherichia coli: a GTP cyclohydrolase I (folE) mutant, deficient in pterin synthesis, was rescued by dihydropterins but not by the corresponding oxidized forms. Expression of a trypanosomatid pterin reductase (PTR1) enabled rescue of the mutant by oxidized pterins, establishing that E. coli can take up oxidized pterins but cannot reduce them. Similarly, a GTP cyclohydrolase I (fol2) mutant of yeast (Saccharomyces cerevisiae) was rescued by dihydropterins but not by most oxidized pterins, 6-hydroxymethylpterin being an exception. These results show that the capacity to reduce oxidized pterins is not ubiquitous in folate-synthesizing organisms. If it is lacking, folate precursors or breakdown products that become oxidized will permanently exit the metabolically active pterin pool.
Noiriel
Alexandre
A
Horticultural Sciences Department, University of Florida, Gainesville, Florida 32611, USA.
Naponelli
Valeria
V
Gregory
Jesse F
JF
Hanson
Andrew D
AD
D017360:Arabidopsis / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D006136:GTP Cyclohydrolase / Q000235:genetics; D018551:Solanum lycopersicum / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D018532:Pisum sativum / Q000378:metabolism; D010936:Plant Extracts / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D010944:Plants / Q000378:metabolism*; D011622:Pterins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
D010936:Plant Extracts; D010940:Plant Proteins; D011622:Pterins; D006136:GTP Cyclohydrolase