HORT640 - Metabolic Plant Physiology
Ammonia Assimilation and Recycling
Tetrahydrofolate involvement in glycine and serine metabolism
Tetrahydrofolate-dependent glycine and serine metabolism are closely linked. Tetrahydrofolate (THF) allows transfer of the alpha-carbon of glycine through glycine decarboxylase (GDC) activity for serine biosynthesis by the serine hydroxymethyltransferase (SHMT) [serine transhydroxymethylase or glycine hydroxymethyltransferase] reaction:
Glycine decarboxylase complex [EC 220.127.116.11/18.104.22.168]
Gly + NAD+ + THF <---> 5,10-methylene-THF + NADH + NH3 + CO2
Serine hydroxymethyltransferase [EC 22.214.171.124]
5,10-methylene-THF + Gly <---> Ser + THF
In C3 plants, the GDC activity is greater than that of SHMT activity in leaf mitochondria, which results in the maintenance of high levels of 5,10-methylene-THF; thus the equilibrium of the SHMT reaction is shifted in favor of serine synthesis, which enables recycling of THF for continuous operation of the GDC reaction during photorespiration.
Formate is a potential alternative single-carbon source for the production of the 5,10-methylene-THF required for serine synthesis.
10-Formyl-THF synthetase (SYN) [EC 126.96.36.199]
Formate + THF + ATP <---> 10-formyl-THF + ADP + Pi
5,10-Methenyl-THF cyclohydrolase (CYC) [EC 188.8.131.52]
10-formyl-THF + H+ <---> 5,10-methenyl-THF + H2O
5,10-Methylene-THF dehydrogenase (DHY) [EC 184.108.40.206 and EC 220.127.116.11]
5,10-methenyl-THF + NADPH <---> 5,10-methylene-THF + NADP+ (EC 18.104.22.168)
5,10-methenyl-THF + NADH <---> 5,10-methylene-THF + NAD+ (EC 22.214.171.124)
These three enzymes are predominantly cytosolic; mitochondria contain <1% of total SYN, CYC and DHY activities (Chen et al, 1997). In most eukaryotes these three activities occur on a single polypeptide called C1-THF synthase; in plants, however, the synthetase activity occurs on a separate protein moiety from that of the cyclohydrolase and reductase, which occur on a bifunctional protein (Prabhu et al, 1996). Possible pathways of formate production in higher plants are described by Hourton-Cabass et al (1998). These include non-enzymic, hydrogen peroxide mediated decarboxylation of glyoxylate during photorespiration, synthesis from methanol (via formaldehyde), synthesis from glycolytic products, and the reverse of the reactions depicted above. Formate dehydrogenase (FDH) [EC 126.96.36.199] catalyzes the oxidation of formate to CO2 and may thus play a key role in regulating formate levels. FDH is a major mitochondrial protein in potato, and is induced by formate, methanol, and various stresses, including anoxia (Hourton-Cabassa et al, 1998), and iron deficiency (Suzuki et al, 1998).
5,10-Methylene-THF is further reduced to 5-methyl-THF by 5,10-methylenetetrahydrofolate reductase [EC 188.8.131.52 and EC 184.108.40.206]. 5-Methyl-THF is exclusively used in methionine synthesis in the reaction catalyzed by methionine synthase [EC 220.127.116.11] (see also methionine synthesis and the activated methyl cycle under Sulfate uptake and assimilation).
Tetrahydrofolic acid (THF) is synthesized from 6-hydroxymethydihydropteridin via the intermediates 6-hydroxymethyldihydropteridin diphosphate, dihydropteroic acid, and dihydrofolic acid (Prabhu et al, 1998). The enzymes catalyzing this reaction sequence
are: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) [EC 18.104.22.168], dihydropteroate synthase (DHPS) [EC 22.214.171.124], dihydrofolate synthase (DHFS) [EC 126.96.36.199], and dihydrofolate reductase (DHFR) [EC 188.8.131.52], respectively (Prabhu et al, 1998). Folylpolyglutamate synth(et)ase (FPGS) [EC 184.108.40.206] then adds a polyglutamyl tail to THF (Prabhu, 1998). Methotrexate and aminopterin are potent inhibitors of DHFR in Arabidopsis (Prabhu et al, 1998).
see also: Interfaces between photorespiration, one-carbon, methionine and S-adenosylmethionine metabolism
Hourton-Cabassa C, Ambard-Bretteville F, Moreau F, de Virville JD, Remy R, des Francs-Small CC 1998 Stress induction of mitochondrial formate dehydrogenase in potato leaves. Plant Physiol. 116: 627-635.
Prabhu V, Chatson KB, Abrams GD, King J 1996 13C Nuclear magnetic resonance detection of interactions of serine hydroxymethyltransferase with C1-tetrahydrofolate synthase and glycine decarboxylase complex activities in Arabidopsis. Plant Physiol. 112: 207-216.
Prabhu V, Chatson KB, Lui H, Abrams GD, King J 1998 Effects of sulfanilamide and methotrexate on 13C fluxes through the glycine decarboxylase/serine hydroxymethyltransferase enzyme system in Arabidopsis. Plant Physiol. 116: 137-144.
Suzuki K, Itai R, Suzuki K, Nakanishi H, Nishizawa NK, Yoshimura E, Mori S 1998 Formate dehydrogenase, an enzyme of anaerobic metabolism, is induced by iron deficiency in barley roots. Plant Physiol. 116: 725-732.
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