Cytoplasmic serine hydroxymethyltransferase regulates the metabolic partitioning of methylenetetrahydrofolate but is not essential in mice

被引：118

作者：

MacFarlane, Amanda J. ^{[1
]}

Liu, Xiaowen ^{[1
]}

Perry, Cheryll A. ^{[1
]}

Flodby, Per ^{[1
]}

Allen, Robert H. ^{[2
,3
]}

Stabler, Sally P. ^{[2
,3
]}

Stover, Patrick J. ^{[1
]}

机构：

[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

[2] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA

[3] Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO 80262 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 38期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1074/jbc.M802671200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The hydroxymethyl group of serine is a primary source of tetrahydrofolate (THF)-activated one-carbon units that are required for the synthesis of purines and thymidylate and for S-adenosylmethionine (AdoMet)-dependent methylation reactions. Serine hydroxylmethyltransferase (SHMT) catalyzes the reversible and THF-dependent conversion of serine to glycine and 5,10-methylene-THF. SHMT is present in eukaryotic cells as mitochondrial SHMT and cytoplasmic (cSHMT) isozymes that are encoded by distinct genes. In this study, the essentiality of cSHMT-derived THF-activated one-carbons was investigated by gene disruption in the mouse germ line. Mice lacking cSHMT are viable and fertile, demonstrating that cSHMT is not an essential source of THF-activated one-carbon units. cSHMT-deficient mice exhibit altered hepatic AdoMet levels and uracil content in DNA, validating previous in vitro studies that indicated this enzyme regulates the partitioning of methylenetetrahydrofolate between the thymidylate and homocysteine remethylation pathways. This study suggests that mitochondrial SHMT-derived one-carbon units are essential for folate-mediated one-carbon metabolism in the cytoplasm.

引用

页码：25846 / 25853

页数：8