ArticleFrontiers in oncology2022
The regulatory mechanisms of proline and hydroxyproline metabolism: Recent advances in perspective.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- "L-Ornithine Liposomal Nanoparticles Targeting the Proline Cycle: A Mechanistic Perspective for Ammonia-Driven Hepatic Encephalopathy".Cell biochemistry and biophysics · 2026Review
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Photoreceptor deletion of pyruvate dehydrogenase E1 subunit α1 induces retinal degeneration and reprograms retinal metabolism.Molecular metabolism · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Mitochondrial Dysfunctions in Human Primary Coenzyme QBiomolecules · 2026Review
- Salvianolic Acid B Exerts Antiphotoaging Effect on Ultraviolet B-Irradiated Human Keratinocytes by Alleviating Oxidative Stress via SIRT1 Protein.Chinese journal of integrative medicine · 2025Article
- The facilitated osteogenic differentiation by extracellular proline treatment in in vitro cell cultivation using MC3T3E1 and hPDLF.Genes & genomics · 2025Article
- The new insight into the role of hydroxyproline in metabolism of cancer cells.Frontiers in cell and developmental biology · 2025Review
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- Brain transcriptomic, metabolic and mitohormesis properties associated with N-propargylglycine treatment: A prevention strategy against neurodegeneration.Brain research · 2024Article
- The Urinary Metabolome of Newborns with Perinatal Complications.Metabolites · 2024Article
- The plasma metabolome of long COVID patients two years after infection.Scientific reports · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For diverse human tumors, growth and metastasis are dependent on proline synthesis, but the mechanisms underlying this association are not clear. Proline incorporated into collagen is primarily synthesized from glutamine. Thus, rates of collagen synthesis are modulated by the enzymes of proline synthesis. On the other hand, the hydroxylation of collagen proline requires αKG, ascorbate and ferrous iron, substrates necessary for the epigenetic demethylation of DNA and histones. The metabolic relationship of proline and hydroxyproline degradation are initiated by distinct dehydrogenases but the respective oxidized products, P5C and OH-P5C are substrates for P5C Reductase and P5C Dehydrogenase allowing for mutual competition. This provides a model by which proline synthesis in cancer plays a role in reprogramming gene expression. The metabolism of proline and hydroxyproline are also linked to the HIF response to hypoxia. Hypoxia increased the expression of ALDH18A1, which is the limiting step in proline and collagen synthesis. Hydroxyproline increases levels of HIF-1α presumably by inhibiting its degradation. These new findings allow the suggestion that there is a regulatory axis from glutamine to proline and collagen synthesis, and the release of free hydroxyproline can feed back on the HIF pathway.
Indexed as
Identifiers
What OpenQuestion holds
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.