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Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae.
J Biol Chem. 2000 Oct 06; 275(40):30987-95.JB

Abstract

One-carbon metabolism in yeast is an essential process that relies on at least one of three one-carbon donor molecules: serine, glycine, or formate. By a combination of genetics and biochemistry we have shown how cells regulate the balance of one-carbon flow between the donors by regulating cytoplasmic serine hydroxymethyltransferase activity in a side reaction occurring in the presence of excess glycine. This control governs the level of 5,10-methylene tetrahydrofolate (5,10-CH(2)-H(4)folate) in the cytoplasm, which has a direct role in signaling transcriptional control of the expression of key genes, particularly those encoding the unique components of the glycine decarboxylase complex (GCV1, GCV2, and GCV3). Based on these and other observations, we propose a model for how cells balance the need to supplement their one-carbon pools when charged folates are limiting or when glycine is in excess. We also propose that under normal conditions, cytoplasmic 5,10-CH(2)-H(4)folate is mainly directed to generating methyl groups via methionine, whereas one-carbon units generated from glycine in mitochondria are more directed to purine biosynthesis. When glycine is in excess, 5, 10-CH(2)-H(4)folate is decreased, and the regulation loop shifts the balance of generation of one-carbon units into the mitochondrion.

Authors+Show Affiliations

School of Biochemistry and Molecular Genetics and the NMR Facility, The University of New South Wales, Sydney, New South Wales 2052, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10871621

Citation

Piper, M D., et al. "Regulation of the Balance of One-carbon Metabolism in Saccharomyces Cerevisiae." The Journal of Biological Chemistry, vol. 275, no. 40, 2000, pp. 30987-95.
Piper MD, Hong SP, Ball GE, et al. Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae. J Biol Chem. 2000;275(40):30987-95.
Piper, M. D., Hong, S. P., Ball, G. E., & Dawes, I. W. (2000). Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae. The Journal of Biological Chemistry, 275(40), 30987-95.
Piper MD, et al. Regulation of the Balance of One-carbon Metabolism in Saccharomyces Cerevisiae. J Biol Chem. 2000 Oct 6;275(40):30987-95. PubMed PMID: 10871621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of the balance of one-carbon metabolism in Saccharomyces cerevisiae. AU - Piper,M D, AU - Hong,S P, AU - Ball,G E, AU - Dawes,I W, PY - 2000/6/29/pubmed PY - 2001/2/28/medline PY - 2000/6/29/entrez SP - 30987 EP - 95 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 275 IS - 40 N2 - One-carbon metabolism in yeast is an essential process that relies on at least one of three one-carbon donor molecules: serine, glycine, or formate. By a combination of genetics and biochemistry we have shown how cells regulate the balance of one-carbon flow between the donors by regulating cytoplasmic serine hydroxymethyltransferase activity in a side reaction occurring in the presence of excess glycine. This control governs the level of 5,10-methylene tetrahydrofolate (5,10-CH(2)-H(4)folate) in the cytoplasm, which has a direct role in signaling transcriptional control of the expression of key genes, particularly those encoding the unique components of the glycine decarboxylase complex (GCV1, GCV2, and GCV3). Based on these and other observations, we propose a model for how cells balance the need to supplement their one-carbon pools when charged folates are limiting or when glycine is in excess. We also propose that under normal conditions, cytoplasmic 5,10-CH(2)-H(4)folate is mainly directed to generating methyl groups via methionine, whereas one-carbon units generated from glycine in mitochondria are more directed to purine biosynthesis. When glycine is in excess, 5, 10-CH(2)-H(4)folate is decreased, and the regulation loop shifts the balance of generation of one-carbon units into the mitochondrion. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/10871621/Regulation_of_the_balance_of_one_carbon_metabolism_in_Saccharomyces_cerevisiae_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=10871621 DB - PRIME DP - Unbound Medicine ER -