33 Questions
What are the properties of Rapamycin?
Antibiotic, antifungal, immunosuppressant, and used to coat stents
Where is Rapamycin derived from?
Streptomyces hygroscopicus (bacterium)
What does Rapamycin inhibit?
mTORC1 master regulator
What is the major pathway for selective protein degradation?
The Ubiquitin-Proteasome Pathway
Which enzyme is responsible for attaching ubiquitin to the amino group of lysine side chains?
Ligases E1, E2, E3
What is the energy requirement for degrading a peptide bond in the proteasome?
1 ATP/peptide bond
At what pH do hydrolases function in the lysosome?
Acidic pH
What is the purpose of synthesizing pepsinogen as an inactive precursor?
To prevent self-digestion in the cell
What is the main reason for the selective uptake and degradation of particular proteins during cellular starvation?
To produce amino acids for other uses
What is the role of ubiquitin in the Ubiquitin-Proteasome Pathway?
To tag proteins targeted for degradation
What is the function of the proteasome in protein degradation?
Degrades proteins in a large multi-subunit complex
What is the primary function of the mechanistic Target of Rapamycin (mTOR) at a cellular level?
Controlling functions related to survival, replication, and maintaining cellular homeostasis
Which pathway has downstream effects on metabolism, proliferation, cell survival, growth, and angiogenesis?
PI3K-Akt-mTOR pathway
What is the role of the mTOR complex 1 in cellular metabolism?
Promoting anabolism and decreasing catabolism
What is the effect of mTOR on mRNA translation and protein synthesis?
Stimulating through posttranslational modifications such as phosphorylation
Which cellular process is regulated by the PI3K-Akt-mTOR pathway?
Protein synthesis
What is the effect of Rapamycin on lifespan in studies on C. elegans, yeast, and Drosophila?
It has been shown to extend lifespan
What is the primary function of Rapamune as a drug?
Immunosuppressant and anticancer drug
What is the significance of the PI3K-Akt-mTOR pathway in cellular signaling?
It has downstream effects on metabolism, proliferation, cell survival, growth, and angiogenesis
What is the central role of mTOR in cellular metabolism and growth?
Regulating protein and lipid biosynthesis
What is the function of the Ubiquitin-Proteasome Pathway?
The Ubiquitin-Proteasome Pathway is a major pathway for selective protein degradation.
What is the role of ubiquitin in the Ubiquitin-Proteasome Pathway?
Ubiquitin is a 76 amino acid protein that is attached by ligases E1, E2, E3 to the amino group of lysine side chains, leading to the polyubiquitination of proteins, which are then recognized by the proteasome for degradation.
How does the proteasome degrade proteins?
The proteasome is a large multi-subunit complex that degrades proteins in a hollow structure. It requires ATP for protein degradation at a rate of 1 ATP per peptide bond.
Why are hydrolases active at acidic pH in the lysosome but not at neutral cytoplasmic pH?
Hydrolases are active at acidic pH in the lysosome as a protective mechanism. They do not function at normal cytosolic pH to prevent active enzymes from degrading macronutrients if the lysosomal membrane ruptures.
How does cellular starvation affect protein degradation?
During cellular starvation, there is selective uptake and degradation of particular proteins, including those with specific amino acid sequences. These proteins are sacrificed to produce amino acids for other uses.
What is the significance of the ATP requirement for protein degradation in the proteasome?
The ATP requirement for protein degradation in the proteasome is less energy-dense than the requirement for protein synthesis.
Why is the selective uptake and degradation of particular proteins important during cellular starvation?
The selective uptake and degradation of particular proteins during cellular starvation allows for the production of amino acids for other uses, contributing to cellular survival.
Explain the role of mTOR in regulating cellular metabolism and growth at a molecular level.
mTOR integrates signals related to nutrient availability, energy, and growth factors to regulate cellular metabolism and growth, with a central role in protein and lipid biosynthesis.
Describe the significance of the PI3K-Akt-mTOR pathway in cellular signaling.
The PI3K-Akt-mTOR pathway is an intracellular signal transduction pathway with downstream effects on metabolism, proliferation, cell survival, growth, and angiogenesis.
Discuss the impact of Rapamycin on lifespan based on studies involving C. elegans, yeast, and Drosophila.
Rapamycin has been shown to extend lifespan in studies on C. elegans, yeast, and Drosophila, and is currently undergoing clinical trials in dogs.
Explain the role of the mTOR complex 1 in cellular metabolism.
The mTOR complex 1 is a central regulator of cell growth and metabolism, promoting anabolism and decreasing catabolism, and is sensitive to cellular energy status.
Discuss the mechanisms by which mTOR stimulates mRNA translation and protein synthesis.
mTOR stimulates mRNA translation and protein synthesis through posttranslational modifications such as phosphorylation, and is involved in muscle hypertrophy, atrophy, and growth.
Discuss the relationship between Rapamycin, cellular energy status, and the mTOR complex 1.
Rapamycin affects the mTOR complex 1, which is sensitive to cellular energy status, thereby influencing cell growth and metabolism.
Study Notes
Rapamycin and mTOR: Key Regulators in Cell Growth and Metabolism
- Suren Shigal (1932-2003) identified and isolated Rapamycin, a drug with anti-fungal and immunosuppressant properties, which was sent to the National Cancer Institute.
- Wyeth and Ayerst merged, leading to the resurrection of Suren's research, and the development of Rapamune as an immunosuppressant and anticancer drug, approved by the FDA in 1999.
- Rapamycin has been shown to extend lifespan in studies on C. elegans, yeast, and Drosophila, and is currently undergoing clinical trials in dogs.
- The mechanistic Target of Rapamycin (mTOR) is a key regulator at a cellular level, controlling functions related to survival, replication, and maintaining cellular homeostasis.
- mTOR integrates signals related to nutrient availability, energy, and growth factors to regulate cellular metabolism and growth, with a central role in protein and lipid biosynthesis.
- The mTOR complex 1 is a central regulator of cell growth and metabolism, promoting anabolism and decreasing catabolism, and is sensitive to cellular energy status.
- The PI3K-Akt-mTOR pathway is an intracellular signal transduction pathway with downstream effects on metabolism, proliferation, cell survival, growth, and angiogenesis.
- mTOR stimulates mRNA translation and protein synthesis through posttranslational modifications such as phosphorylation, and is involved in muscle hypertrophy, atrophy, and growth.
- Protein synthesis in the body is energy-expensive and regulated by the PI3K-Akt-mTOR pathway, with contributions from various cellular components and processes.
- Protein degradation, or proteolysis, is crucial in determining protein levels within cells and occurs through the ubiquitin-proteasome pathway, lysosomal proteolysis, and extracellular proteolysis.
Rapamycin and mTOR: Key Regulators in Cell Growth and Metabolism
- Suren Shigal (1932-2003) identified and isolated Rapamycin, a drug with anti-fungal and immunosuppressant properties, which was sent to the National Cancer Institute.
- Wyeth and Ayerst merged, leading to the resurrection of Suren's research, and the development of Rapamune as an immunosuppressant and anticancer drug, approved by the FDA in 1999.
- Rapamycin has been shown to extend lifespan in studies on C. elegans, yeast, and Drosophila, and is currently undergoing clinical trials in dogs.
- The mechanistic Target of Rapamycin (mTOR) is a key regulator at a cellular level, controlling functions related to survival, replication, and maintaining cellular homeostasis.
- mTOR integrates signals related to nutrient availability, energy, and growth factors to regulate cellular metabolism and growth, with a central role in protein and lipid biosynthesis.
- The mTOR complex 1 is a central regulator of cell growth and metabolism, promoting anabolism and decreasing catabolism, and is sensitive to cellular energy status.
- The PI3K-Akt-mTOR pathway is an intracellular signal transduction pathway with downstream effects on metabolism, proliferation, cell survival, growth, and angiogenesis.
- mTOR stimulates mRNA translation and protein synthesis through posttranslational modifications such as phosphorylation, and is involved in muscle hypertrophy, atrophy, and growth.
- Protein synthesis in the body is energy-expensive and regulated by the PI3K-Akt-mTOR pathway, with contributions from various cellular components and processes.
- Protein degradation, or proteolysis, is crucial in determining protein levels within cells and occurs through the ubiquitin-proteasome pathway, lysosomal proteolysis, and extracellular proteolysis.
Test your knowledge about the key regulators in cell growth and metabolism with this quiz on Rapamycin and mTOR. Learn about the history of Rapamycin, its applications, and the role of mTOR in cellular functions such as survival, metabolism, and protein synthesis.
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