One-carbon metabolism during the menstrual cycle and pregnancy
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 articleSubject
HumansCarbon
Vitamin B 12
Folic Acid
Estradiol
Homocysteine
S-Adenosylmethionine
Menstrual Cycle
Pregnancy
Female
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https://hdl.handle.net/10161/26375Published Version (Please cite this version)
10.1371/journal.pcbi.1009708Publication 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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Show full item recordScholars@Duke
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
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
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