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One-carbon metabolism during the menstrual cycle and pregnancy

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Date
2021-12
Authors
Reed, Michael
Nijhout, Frederik
Kim, Ruby
Editor
Mendes, Pedro
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Abstract
Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.
Type
Journal article
Subject
Humans
Carbon
Vitamin B 12
Folic Acid
Estradiol
Homocysteine
S-Adenosylmethionine
Menstrual Cycle
Pregnancy
Female
Permalink
https://hdl.handle.net/10161/26375
Published Version (Please cite this version)
10.1371/journal.pcbi.1009708
Publication Info
Reed, Michael; Nijhout, Frederik; & Kim, Ruby (2021). One-carbon metabolism during the menstrual cycle and pregnancy. PLoS Computational Biology, (to appear)(12). pp. e1009708. 10.1371/journal.pcbi.1009708. Retrieved from https://hdl.handle.net/10161/26375.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Nijhout

H. Frederik Nijhout

John Franklin Crowell Distinguished Professor of Biology
Fred Nijhout is broadly interested in developmental physiology and in the interactions between development and evolution. He has several lines of research ongoing in his laboratory that on the surface may look independent from one another, but all share a conceptual interest in understanding how complex traits arise through, and are affected by, the interaction of genetic and environmental factors. 1) The control of polyphenic development in insects. This work attempts to understand how the inse
Reed

Michael C. Reed

Arts & Sciences Distinguished Professor of Mathematics
Professor Reed is engaged in a large number of research projects that involve the application of mathematics to questions in physiology and medicine. He also works on questions in analysis that are stimulated by biological questions. For recent work on cell metabolism and public health, go to sites@duke.edu/metabolism. Since 2003, Professor Reed has worked with Professor Fred Nijhout (Duke Biology) to use mathematical methods to understan
Alphabetical list of authors with Scholars@Duke profiles.
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