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

Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon metabolism in... Abstract 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. serine hydroxymethyltransferase methylene tetrahydrofolate reductase methenyltetrahydrofolate synthase methionine synthase tetrahydrofolate Footnotes Address for reprint requests and other correspondence: M. R. Narkewicz, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital B290, 1056 East 19th Ave., Denver, CO 80218 (E-mail: narkewicz.michael@tchden.org ). 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. Copyright © 2001 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

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

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
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Abstract

Abstract 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. serine hydroxymethyltransferase methylene tetrahydrofolate reductase methenyltetrahydrofolate synthase methionine synthase tetrahydrofolate Footnotes Address for reprint requests and other correspondence: M. R. Narkewicz, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital B290, 1056 East 19th Ave., Denver, CO 80218 (E-mail: narkewicz.michael@tchden.org ). 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. Copyright © 2001 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: May 1, 2001

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