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Questions and Answers
Which of the following are major proteolytic systems involved in muscle protein degradation? (Select all that apply)
Which of the following are major proteolytic systems involved in muscle protein degradation? (Select all that apply)
- Autophagy-lysosomal system (correct)
- Calpain system (correct)
- Ubiquitin-proteasome system (correct)
- Caspases
What is the primary function of the ubiquitin-proteasome pathway?
What is the primary function of the ubiquitin-proteasome pathway?
Protein degradation
What is Atg7's role in autophagy?
What is Atg7's role in autophagy?
- Initiation of autophagy (correct)
- Initiation of protein synthesis
- Regulating muscle atrophy
- Degradation of proteins
Muscle atrophy occurs due to increased use.
Muscle atrophy occurs due to increased use.
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Name the two types of muscle fibers that have higher rates of protein synthesis.
Name the two types of muscle fibers that have higher rates of protein synthesis.
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The _____ system is responsible for the degradation of long-lived and misfolded proteins.
The _____ system is responsible for the degradation of long-lived and misfolded proteins.
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What kind of response occurs during fasting or starvation related to muscle?
What kind of response occurs during fasting or starvation related to muscle?
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Study Notes
Major Pathways Involved in Atrophy and Recovery
- Muscle Protein Degradation:
- Major Proteolytic Systems:
- Ubiquitin-Proteasome System (UPS): Degrades proteins, including short-lived proteins, through poly-ubiquitination
- Autophagy-Lysosomal System: Degrades longer-lived proteins, aggregates, organelles (mitochondria, ER), lipids, and glycogen.
- Calpain System: Degrades specific proteins
- Caspases: Degrade specific proteins involved in apoptosis
- Basal Protein Degradation: Rates vary between fiber types
- Slow-twitch (Type 1): Higher protein synthesis and degradation rates
- Fast-twitch (Type 2): Lower protein synthesis and degradation rates, vary by subtype (2a, 2x, 2b)
- Major Proteolytic Systems:
Acute Muscle Atrophy
- Decreased Use:
- Fiber Type Shift: Changes in fiber type can occur with disuse, favoring fast-twitch fibers
- Fasting/Starvation: Muscle protein breakdown is increased
- Signal Regulation: Major signals that regulate muscle atrophy are linked to protein degradation:
- Atrogin-1 and MURF-1: Are muscle-specific E3 ubiquitin ligases that are upregulated in atrophy
Recovery from Atrophy
- Satellite Cells:
- Their role in recovery from atrophy is still under investigation
Ubiquitin-Proteasome System (UPS)
- Key Proteins: E3 ubiquitin ligases, such as Atrogin-1 and MURF-1, are specific to skeletal and heart muscles.
- Process: Poly-ubiquitinated proteins are targeted for degradation by the proteasome.
Autophagy-Lysosome System
- Macroautophagy: A conserved process that involves the formation of autophagosomes.
- Function: Degrades long-lived proteins, misfolded proteins, and organelles (mitochondria).
- Key Proteins: ATg7 and ULKs involved in the initiation of autophagy.
Autophagy and Protein Accumulation
- Disruption of Autophagy: Disruption leads to accumulation of ubiquitinated proteins in skeletal muscle.
- ATG7: Plays a crucial role in the initiation of autophagy.
- Atg7 Deletion: Causes a major disruption in the process.
Mitochondrial Content and Autophagy
- Mitochondrial Biogenesis and Content: Correlates with basal autophagy in muscles.
Protein Synthesis Assessment
- Methods:
- Heavy Amino Acid Labeling:
- Heavy water labeling:
- Puromycin Labeling: Used to measure protein synthesis rates in different muscle fibers
- Synthesis Rates: Type IIa and Type I fibers have higher rates of protein synthesis compared to Type IIx and Iib fibers.
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