One-carbon metabolism during the menstrual cycle and pregnancy.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
22
06
2021
accepted:
01
12
2021
revised:
07
01
2022
pubmed:
17
12
2021
medline:
12
2
2022
entrez:
16
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34914693
doi: 10.1371/journal.pcbi.1009708
pii: PCOMPBIOL-D-21-01166
pmc: PMC8741061
doi:
Substances chimiques
Homocysteine
0LVT1QZ0BA
Estradiol
4TI98Z838E
Carbon
7440-44-0
S-Adenosylmethionine
7LP2MPO46S
Folic Acid
935E97BOY8
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009708Subventions
Organisme : NIMH NIH HHS
ID : R01 MH106563
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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