Journal
ANNUAL REVIEW OF GENETICS, VOL 49
Volume 49, Issue -, Pages 553-575Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-genet-112414-055257
Keywords
metabolic network; feedback loop; homeostasis; gene regulation; flux balance analysis; Caenorhabditis elegans
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Funding
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM082971] Funding Source: NIH RePORTER
- NIGMS NIH HHS [R01 GM082971] Funding Source: Medline
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Metabolic networks are extensively regulated to facilitate tissue-specific metabolic programs and robustly maintain homeostasis in response to dietary changes. Homeostatic metabolic regulation is achieved through metabolite sensing coupled to feedback regulation of metabolic enzyme activity or expression. With a wealth of transcriptomic, proteomic, and metabolomic data available for different cell types across various conditions, we are challenged with understanding global metabolic network regulation and the resulting metabolic outputs. Stoichiometric metabolic network modeling integrated with omics data has addressed this challenge by generating nonintuitive, testable hypotheses about metabolic flux rewiring. Model organism studies have also yielded novel insight into metabolic networks. This review covers three topics: the feedback loops inherent in metabolic regulatory networks, metabolic network modeling, and interspecies studies utilizing Caenorhabditis elegans and various bacterial diets that have revealed novel metabolic paradigms.
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