scholarly journals Effects of tetrahydrofolate polyglutamates on the kinetic parameters of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria

1993 ◽  
Vol 292 (2) ◽  
pp. 425-430 ◽  
Author(s):  
V Besson ◽  
F Rebeille ◽  
M Neuburger ◽  
R Douce ◽  
E A Cossins
Keyword(s):  
Kinetic Parameters ◽  
Serine Hydroxymethyltransferase ◽  
Affinity Constant ◽  
Plant Tissues ◽  
Glycine Decarboxylase ◽  
Glycine Cleavage System ◽  
Matrix Space ◽  
The Matrix ◽  
Order Of Magnitude ◽  
Glycine Cleavage

Plant tissues contain highly conjugated forms of folate. Despite this, the ability of plant folate-dependent enzymes to utilize tetrahydrofolate polyglutamates has not been examined in detail. In leaf mitochondria, the glycine-cleavage system and serine hydroxymethyltransferase, present in large amounts in the matrix space and involved in the photorespiratory cycle, necessitate the presence of tetrahydrofolate as a cofactor. The aim of the present work was to determine whether glutamate chain length (one to six glutamate residues) influenced the affinity constant for tetrahydrofolate and the maximal velocities displayed by these two enzymes. The results show that the affinity constant decreased by at least one order of magnitude when the tetrahydrofolate substrate contained three or more glutamate residues. In contrast, maximal velocities were not altered in the presence of these substrates. These results are consistent with analyses of mitochondrial folates which revealed a pool of polyglutamates dominated by tetra and pentaglutamates. The equilibrium constant of the serine hydroxymethyltransferase suggests that, during photorespiration, the reaction must be permanently pushed toward the formation of serine (the unfavourable direction) to allow the recycling of tetrahydrofolate necessary for the operation of the glycine decarboxylase T-protein.

scholarly journals Resolution and characterization of the glycine-cleavage reaction in pea leaf mitochondria. Properties of the forward reaction catalysed by glycine decarboxylase and serine hydroxymethyltransferase

1988 ◽  
Vol 255 (1) ◽  
pp. 169-178 ◽  
Author(s):  
J Bourguignon ◽  
M Neuburger ◽  
R Douce
Keyword(s):  
Pyridoxal Phosphate ◽  
Gel Filtration ◽  
Serine Hydroxymethyltransferase ◽  
Molar Ratios ◽  
Apparent Homogeneity ◽  
The Matrix ◽  
Lipoamide Dehydrogenase ◽  
Glycine Cleavage ◽  
Low Ionic Strength

High-molecular-mass proteins from pea (Pisum sativum) mitochondrial matrix retained on an XM-300 Diaflo membrane (‘matrix extract’) exhibited high rates of glycine oxidation in the presence of NAD+ and tetrahydropteroyl-L-glutamic acid (H4 folate) as long as the medium exhibited a low ionic strength. Serine hydroxymethyltransferase (SHMT) (4 x 53 kDa) and the four proteins of the glycine-cleavage system, including a pyridoxal phosphate-containing enzyme (‘P-protein’ 2 x 97 kDa), a carrier protein containing covalently bound lipoic acid (‘H-protein’ 15.5 kDa), a protein exhibiting lipoamide dehydrogenase activity (‘L-protein’; 2 x 61 kDa) and an H4 folate-dependent enzyme (‘T-protein’ 45 kDa) have been purified to apparent homogeneity from the matrix extract by using gel filtration, ion-exchange and phenyl-Superose fast protein liquid chromatography. Gel filtration on Sephacryl S-300 in the presence of 50 mM-KCl proved to be the key step in disrupting this complex. During the course of glycine oxidation catalysed by the matrix extract a steady-state equilibrium in the production and utilization of 5,10-methylene-H4 folate was reached, suggesting that glycine cleavage and SHMT are linked together via a soluble pool of H4 folate. The rate of glycine oxidation catalysed by the matrix extract was sensitive to the NADH/NAD+ molar ratios, because NADH competitively inhibited the reaction catalysed by lipoamide dehydrogenase.

scholarly journals mTORC1 activity regulates post-translational modifications of glycine decarboxylase to modulate glycine metabolism and tumorigenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rui Liu ◽  
Lin-Wen Zeng ◽  
Rong Gong ◽  
Fanen Yuan ◽  
Hong-Bing Shu ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Ubiquitin Ligase ◽  
Glycine Decarboxylase ◽  
Glycine Cleavage System ◽  
Sirtuin 3 ◽  
Post Translational Modifications ◽  
Mechanistic Target Of Rapamycin ◽  
Glycine Metabolism ◽  
Key Enzyme ◽  
Glycine Cleavage

AbstractGlycine decarboxylase (GLDC) is a key enzyme of glycine cleavage system that converts glycine into one-carbon units. GLDC is commonly up-regulated and plays important roles in many human cancers. Whether and how GLDC is regulated by post-translational modifications is unknown. Here we report that mechanistic target of rapamycin complex 1 (mTORC1) signal inhibits GLDC acetylation at lysine (K) 514 by inducing transcription of the deacetylase sirtuin 3 (SIRT3). Upon inhibition of mTORC1, the acetyltransferase acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes GLDC K514 acetylation. This acetylation of GLDC impairs its enzymatic activity. In addition, this acetylation of GLDC primes for its K33-linked polyubiquitination at K544 by the ubiquitin ligase NF-X1, leading to its degradation by the proteasomal pathway. Finally, we find that GLDC K514 acetylation inhibits glycine catabolism, pyrimidines synthesis and glioma tumorigenesis. Our finding reveals critical roles of post-translational modifications of GLDC in regulation of its enzymatic activity, glycine metabolism and tumorigenesis, and provides potential targets for therapeutics of cancers such as glioma.

Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon metabolism in rabbits

2001 ◽  
Vol 280 (5) ◽  
pp. G873-G878 ◽  
Author(s):  
Henry R. Thompson ◽  
Gayle M. Jones ◽  
Michael R. Narkewicz
Keyword(s):  
Carbon Metabolism ◽  
Specific Activity ◽  
Serine Hydroxymethyltransferase ◽  
Central Position ◽  
Fetal Life ◽  
Glycine Cleavage System ◽  
Hepatic Enzymes ◽  
Methenyltetrahydrofolate Synthetase ◽  
Glycine Cleavage ◽  
One Carbon Metabolism

Serine occupies a central position in folate-dependent, one-carbon metabolism through 5,10-methylenetetrahydrofolate (MTHF) and 5-formyltetrahydrofolate (FTHF). We characterized the ontogeny of the specific activity of key enzymes involved in serine, 5,10-MTHF, and 5-FTHF metabolism: methenyltetrahydrofolate synthetase (MTHFS), MTHF reductase (MTHFR), the glycine cleavage system (GCS), methionine synthase (MS), and serine hydroxymethyltransferase (SHMT) in rabbit liver, placenta, brain, and kidney. In liver, MTHFS activity is low in the fetus (0.36 ± 0.07 nmol · min−1 · mg protein−1), peaks at 3 wk (1.48 ± 0.50 nmol · min−1 · mg protein−1), and then decreases to adult levels (1.13 ± 0.32 nmol · min−1 · mg protein−1). MTHFR activity is highest early in gestation (24.9 ± 2.4 nmol · h−1 · mg protein−1) and declines rapidly by birth (4.7 ± 1.3 nmol · h−1 · mg protein−1). MS is highest during fetal life and declines after birth. Cytosolic SHMT activity does not vary during development, but mitochondrial SHMT peaks at 23 days. GCS activity is high in the fetus and the neonate, declining after weaning. In placenta and brain, all activities are low throughout gestation. Cytosolic and mitochondrial SHMT activities are low in kidney and rise after weaning, whereas MTHFS is low throughout development. These data suggest that the liver is the primary site of activity for these enzymes. Throughout development, there are multiple potential sources for production of 5,10-MTHF, but early in gestation high MTHFR activity and low MTHFS activity could reduce 5,10-MTHF availability.

scholarly journals Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy

2014 ◽  
Vol 59 (11) ◽  
pp. 593-597 ◽  
Author(s):  
Nor Azimah Abdul Azize ◽  
Wan Zurinah Wan Ngah ◽  
Zulhabri Othman ◽  
Norsiah Md Desa ◽  
Chen Bee Chin ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Glycine Decarboxylase ◽  
Glycine Cleavage System ◽  
Glycine Encephalopathy ◽  
Glycine Cleavage
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