L6: Dynamic Regulation Of Protein Expression Flashcards
Why is it important to regulate protein activity in the cell?
Proper balance between protein synthesis and degradation ensures cellular function. Dysregulation can lead to diseases like cancer, neurodegenerative disorders, and lysosomal storage diseases.
What is the role of protein degradation in cellular function?
It balances synthesis, removes damaged proteins, and regulates protein levels to control processes like cell cycle progression or shutting down pathways.
When do proteins get degraded?
- Housekeeping proteins get damaged and need to be replaced
- Misfolded proteins need to be recycled
- Levels of proteins tightly regulated to control function
- In the course of being activated some proteins get cleaved and need to be replaced eg: digestive enzymes that are secreted as zymogens
What are the two main pathways for protein degradation in cells?
Lysosomal degradation
Proteasomal degradation
What are lysosomes?
Lysosomes are membrane-bound organelles in cells that arise from the endoplasmic reticulum.
How is the internal environment of lysosomes maintained?
Lysosomes maintain a highly acidic environment (pH 4) through proton pumps that pump H⁺ ions into the lysosome, reducing the pH.
What is the function of lysosomal enzymes?
Lysosomal enzymes (acid hydrolases) degrade proteins, nucleic acids, carbohydrates, and lipids. They are only active at low pH, which protects cytosolic proteins if these enzymes leak out.
What types of materials do lysosomes degrade?
Lysosomes degrade any biological material, including proteins, nucleic acids, carbohydrates, lipids, and any organelle or organism released into the lysosome.
Why is the acidic environment of lysosomes crucial for their function?
The acidic environment ensures that the degradative enzymes are only active inside the lysosome. If enzymes leak into the cytosol, the neutral pH (7) of the cytoplasm renders them ineffective, preventing unwanted degradation of cellular components.
How do lysosomes degrade proteins?
degrades proteins that are imported into the lysosome, including damaged organelles and other biological materials.
What happens when there are defects in lysosomal enzymes?
Defects in lysosomal enzymes can cause lysosomal storage diseases, where unwanted biomolecules accumulate in cells, leading to severe cellular dysfunction and often catastrophic effects, depending on which enzyme is lost.
What is autophagy and why is it important
Autophagy is a process where cells degrade and recycle damaged organelles and proteins via autophagosomes and deliver them to lysosomes for degradation. It helps protect cells from harmful accumulation of misfolded proteins and damaged organelles.
What is the significance of ubiquitin recycling in the proteasome?
During the degradation process, the ubiquitin molecules are removed from the target protein by the proteasome’s 19S cap and are recycled for further use in marking other proteins for degradation.
How does the proteasome contribute to maintaining cellular protein homeostasis?
By degrading misfolded, damaged, or regulatory proteins, the proteasome ensures that only functional proteins are present in the cell, preventing harmful protein accumulation and maintaining proper cellular function.
What is ubiquitination, and how does it work?
Ubiquitination is a process where ubiquitin is attached to a protein to signal its degradation. It is added on in chains to lysine residues on proteins
How is protein ubiquitination specific and regulated?
Ubiquitination is regulated through a multistep process involving three key enzymes:
E1 (Ubiquitin-activating enzyme) – Activates ubiquitin.
E2 (Ubiquitin-conjugating enzyme) – Transfers ubiquitin.
E3 (Ubiquitin ligase) – Attaches ubiquitin to the target protein, providing substrate specificity.
What is the ubiquitin-proteasome system (UPS)?
UPS targets proteins for degradation by attaching ubiquitin to Lysine residues. This poly-ubiquitinated protein is recognized by the proteasome, which degrades it into peptides.
