Related Experiment Video
Updated: Jun 13, 2026
06:32
Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts
Published on: April 13, 2022
Proline metabolism and microenvironmental stress.
James M Phang1, Wei Liu, Olga Zabirnyk
1Metabolism and Cancer Susceptibility Section, Laboratory of Comparative Carcinogenesis, Center for Cancer Research, NCI at Frederick, Frederick, Maryland 21702, USA. phangj@mail.nih.gov
Annual Review of Nutrition
|April 27, 2010
Summary
Proline metabolism, regulated by proline oxidase, plays a key role in cellular responses to stress and cancer. Its reduced levels in tumors suggest a tumor suppressor function, linking obesity and cancer risk.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Signaling
Background:
- Proline is a unique amino acid metabolized by specific enzymes involved in stress response and signaling.
- Collagen serves as a major proline reservoir, with its degradation releasing proline during stress.
- Proline oxidase initiates proline degradation and is regulated by key cellular pathways.
Purpose of the Study:
- To elucidate the role of proline metabolism and proline oxidase in cellular stress response and cancer.
- To investigate the regulatory mechanisms and downstream effects of proline oxidase.
- To explore the link between proline metabolism, obesity, and cancer risk.
Main Methods:
- Analysis of proline metabolic pathways and enzyme regulation.
- Investigation of proline oxidase induction by signaling molecules (p53, PPARgamma, AMPK).
- Assessment of proline metabolism's impact on cellular processes (cell cycle, autophagy, apoptosis) and ATP production.
Main Results:
- Proline metabolism generates reactive oxygen species (ROS) and influences cell cycle, autophagy, and apoptosis.
- Proline oxidase activity supports ATP production for survival under nutrient stress.
- Pyrroline-5-carboxylate, a proline metabolite, influences hypoxia-inducible factor-1alpha stability.
Conclusions:
- Proline oxidase acts as a tumor suppressor, evidenced by its decreased levels in tumors and its regulatory roles.
- Specific microRNAs mediate the decrease in proline oxidase levels in cancer.
- Proline oxidase links oxidized LDL, autophagy, obesity, and cancer risk, highlighting a critical metabolic signaling pathway.
Related Concept Videos
01:30Other Stress Responses in Bacteria
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
01:23Stringent Response in E. coli
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:21Overview of Protein Metabolism
Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
01:28Biosynthesis of Nucleic Acids
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...