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Polyamine Metabolism and Applications
Research Guide
What is Polyamine Metabolism and Applications?
Polyamine metabolism refers to the biochemical pathways involving the synthesis, catabolism, and regulation of polyamines such as putrescine, spermidine, and spermine, which play essential roles in cellular growth, differentiation, and disease processes with applications in cancer therapy, aging research, and food science.
The field encompasses 53,843 works examining polyamines and biogenic amines in biological contexts including cancer, aging, autophagy, and plant development. Polyamines derive from amino acids like arginine and participate in pathways such as mTOR signaling and amino acid metabolism. Key papers highlight their links to cellular functions and therapeutic potential.
Topic Hierarchy
Research Sub-Topics
Polyamines in Cancer Biology
This sub-topic investigates polyamine synthesis (ODC, SSAT), catabolism, and transport dysregulation in tumorigenesis and metastasis. Researchers target polyamine pathway inhibitors like DFMO for chemotherapy.
Polyamines and Cellular Autophagy
Studies explore spermidine/spermine-induced macroautophagy, mitophagy, and links to mTOR/AMPK signaling. Experiments use polyamine analogs to modulate autophagic flux in aging and neurodegeneration models.
Polyamine Homeostasis Regulation
Researchers analyze transcriptional/post-transcriptional controls of ODC, AdoMetDC, and SMS/SAT1 by feedback mechanisms and oncogenes. Cross-talk with polyamine-sensing hypusination of eIF5A is examined.
Polyamines in Plant Development
This area covers polyamine roles in embryogenesis, root/shoot growth, flowering, and stress responses via conjugation to transglutaminases. Transgenic and RNAi studies reveal signaling via nitric oxide.
Biogenic Amines in Food Science
Research focuses on microbial decarboxylation forming histamine/tyramine in fermented foods, detection methods, and degradation strategies. Toxicological thresholds and quality control during storage are assessed.
Why It Matters
Polyamine metabolism influences cancer progression through interactions with mTOR signaling, as shown in "mTOR Signaling in Growth, Metabolism, and Disease" where Saxton and Sabatini (2017) detail how deregulation drives tumor growth, with implications for targeted inhibitors in oncology. In amino acid pathways, Wu and Morris (1998) in "Arginine metabolism: nitric oxide and beyond" explain arginine's conversion to polyamines alongside nitric oxide and urea, affecting vascular health and immune responses with applications in cardiovascular therapies. Early work by Ames and Dubin (1960) in "The Role of Polyamines in the Neutralization of Bacteriophage Deoxyribonucleic Acid" demonstrates polyamines' DNA-stabilizing role, informing antiviral strategies and gene therapy designs.
Reading Guide
Where to Start
"Arginine metabolism: nitric oxide and beyond" by Wu and Morris (1998), as it provides a foundational overview of polyamine synthesis from arginine with clear enzymatic details suitable for newcomers.
Key Papers Explained
Wu and Morris (1998) in "Arginine metabolism: nitric oxide and beyond" establishes polyamine production from arginine, which Inoki et al. (2002) in "TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling" connects to mTOR inhibition; Saxton and Sabatini (2017) in "mTOR Signaling in Growth, Metabolism, and Disease" and Guertin and Sabatini (2007) in "Defining the Role of mTOR in Cancer" build on this to explain disease implications, while Ames and Dubin (1960) in "The Role of Polyamines in the Neutralization of Bacteriophage Deoxyribonucleic Acid" details a core molecular function.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Current research within the 53,843 works emphasizes polyamine roles in autophagy and cancer signaling, as in Levine and Klionsky (2004) and Peinado et al. (2007), with no recent preprints or news indicating focus on therapeutic inhibitors and plant applications persists.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | mTOR Signaling in Growth, Metabolism, and Disease | 2017 | Cell | 7.1K | ✓ |
| 2 | Development by Self-Digestion | 2004 | Developmental Cell | 3.6K | ✓ |
| 3 | A simple and rapid method for the permethylation of carbohydrates | 1984 | Carbohydrate Research | 3.5K | ✕ |
| 4 | Snail, Zeb and bHLH factors in tumour progression: an alliance... | 2007 | Nature reviews. Cancer | 3.1K | ✕ |
| 5 | TSC2 is phosphorylated and inhibited by Akt and suppresses mTO... | 2002 | Nature Cell Biology | 3.0K | ✕ |
| 6 | Amino acids: metabolism, functions, and nutrition | 2009 | Amino Acids | 2.9K | ✕ |
| 7 | Defining the Role of mTOR in Cancer | 2007 | Cancer Cell | 2.8K | ✓ |
| 8 | Arginine metabolism: nitric oxide and beyond | 1998 | Biochemical Journal | 2.8K | ✓ |
| 9 | The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling t... | 2008 | Science | 2.7K | ✓ |
| 10 | The Role of Polyamines in the Neutralization of Bacteriophage ... | 1960 | Journal of Biological ... | 2.6K | ✓ |
Frequently Asked Questions
What role do polyamines play in arginine metabolism?
Arginine serves as a precursor for polyamines, nitric oxide, urea, proline, glutamate, creatine, and agmatine in animal cells. Wu and Morris (1998) in "Arginine metabolism: nitric oxide and beyond" describe enzymes catalyzing rate-controlling steps in these pathways. This versatility supports protein synthesis and diverse physiological functions.
How are polyamines linked to mTOR signaling?
mTORC1 integrates amino acid signals via Rag GTPases to promote growth and metabolism. Sancak et al. (2008) in "The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1" show Rag proteins mediate this sensing, relevant to polyamine-influenced nutrient pathways. Deregulation occurs in cancers as noted by Guertin and Sabatini (2007) in "Defining the Role of mTOR in Cancer".
What is the function of polyamines in DNA neutralization?
Polyamines neutralize the charge of bacteriophage deoxyribonucleic acid, stabilizing viral structure. Ames and Dubin (1960) in "The Role of Polyamines in the Neutralization of Bacteriophage Deoxyribonucleic Acid" quantify this interaction biochemically. This mechanism extends to eukaryotic DNA packaging and cellular stability.
How does polyamine metabolism relate to autophagy?
Autophagy involves self-digestion processes tied to polyamine-regulated cellular homeostasis. Levine and Klionsky (2004) in "Development by Self-Digestion" connect these to developmental biology. Polyamines influence autophagic flux in aging and cancer contexts within the 53,843 works.
What are the applications of polyamine research in cancer?
Polyamines contribute to tumor progression via epithelial-mesenchymal transition factors. Peinado et al. (2007) in "Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?" link this to polyamine-modulated signaling. Therapeutic targeting appears in mTOR-related papers like Inoki et al. (2002).
Open Research Questions
- ? How do polyamines specifically modulate mTORC1 activity in response to arginine-derived signals?
- ? What mechanisms link polyamine levels to autophagic self-digestion during plant and animal development?
- ? In what ways do polyamines interact with Snail/Zeb factors to drive tumor invasion beyond epithelial phenotypes?
- ? How does TSC2 phosphorylation by Akt influence polyamine synthesis in cancer suppression?
- ? What precise roles do polyamines play in stabilizing DNA structures across viral and cellular contexts?
Recent Trends
The field maintains 53,843 works with sustained interest in polyamine-mTOR intersections, as evidenced by high citations for Saxton and Sabatini (2017, 7123 citations) and Sancak et al. (2008, 2721 citations); no growth rate data or recent preprints/news available, suggesting stable exploration of cancer and amino acid links from Wu and Wu and Morris (1998).
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