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J. Biol. Chem., Vol. 275, Issue 40, 30987-30995, October 6, 2000
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From the School of Biochemistry and Molecular Genetics and the
¶ NMR Facility, The University of New South Wales, Sydney,
New South Wales 2052, Australia
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-CH2-H4folate) 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-CH2-H4folate 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-CH2-H4folate is decreased, and the
regulation loop shifts the balance of generation of one-carbon units
into the mitochondrion.
Regulation of the Balance of One-carbon Metabolism in
Saccharomyces cerevisiae*
,
*
This work was supported by Australian Research Council Grant
A10007007.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by an Australian Postgraduate Award.
§
Present address: Dept. of Microbiology, Columbia University, New
York, NY 10027-6902.
To whom correspondence should be addressed. Tel.:
61-2-9385-2089; Fax: 61-2-9385-1050; E-mail:
i.dawes@unsw.edu.au.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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