ArticleCell metabolism2024
Glycine homeostasis requires reverse SHMT flux.
Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
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- Dietary folic acid coordinates growth and lipid metabolism through gut microbial and one-carbon networks in juvenile mud crab (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Identification of candidate genes and metabolites associated with lactation performance in Kazakh mares using blood multi-omics and machine learning.BMC genomics · 2026Article
- Glycine: The missing link between carbohydrate and xenobiotic metabolism in the maturing human hepatocyte.iScience · 2026Article
- MTHFR functions as a metabolic checkpoint in NSCLC through SLC25A26-mediated SHMT2 inhibition.Cell death & disease · 2026Article
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Heavy water labeling reveals metabolic flexibility of amino acid and polyamine pathways in mammalian cells.Communications chemistry · 2026Article
- Targeting serine/glycine metabolism to attenuate IFN-γ- and IL-22-driven inflammation and hyperproliferation in psoriasis.Cell death discovery · 2026Article
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Pediococcus acidilactici PA-1 Alleviates Diet-Induced Obesity by Modulating Hepatic Amino Acid Metabolism and Gut Microbiota in Mice.Probiotics and antimicrobial proteins · 2026Article
- Integrated miRNAs, Transcriptome, and Metabolome Uncover Underlying Mechanisms for Breast Muscle Metabolic Regulation in Liancheng White and Cherry Valley Ducks.Animals : an open access journal from MDPI · 2026Article
- Serum Amino Acid and Fatty Acid Metabolites as Predictors of Sleep Disorders in Children: A Risk Prediction Model.Biomedicines · 2026Article
- Alternative Pathway for Methyl Supply through the Coupling of SHMT1 and PEMT to Maintain Astrocytic Homeostasis in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Digital twins for in vivo metabolic flux estimations in patients with brain cancer.Cell metabolism · 2026Article
- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Multi-omics analysis reveals the mechanism of Huaganjian in alleviating cholestatic liver fibrosis.Frontiers in pharmacology · 2026Article
- Mitochondrial one-carbon metabolism is required for TGF-β-induced glycine synthesis and fibrotic responses.Nature communications · 2025Article
- Sarcosine decreases in sarcopenia and enhances muscle regeneration and adipose thermogenesis by activating anti-inflammatory macrophages.Nature aging · 2025Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The folate-dependent enzyme serine hydroxymethyltransferase (SHMT) reversibly converts serine into glycine and a tetrahydrofolate-bound one-carbon unit. Such one-carbon unit production plays a critical role in development, the immune system, and cancer. Using rodent models, here we show that the whole-body SHMT flux acts to net consume rather than produce glycine. Pharmacological inhibition of whole-body SHMT1/2 and genetic knockout of liver SHMT2 elevated circulating glycine levels up to eight-fold. Stable-isotope tracing revealed that the liver converts glycine to serine, which is then converted by serine dehydratase into pyruvate and burned in the tricarboxylic acid cycle. In response to diets deficient in serine and glycine, de novo biosynthetic flux was unaltered, but SHMT2- and serine-dehydratase-mediated catabolic flux was lower. Thus, glucose-derived serine synthesis is largely insensitive to systemic demand. Instead, circulating serine and glycine homeostasis is maintained through variable consumption, with liver SHMT2 a major glycine-consuming enzyme.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.