Protein Synthesis and Degradation

turnover

Muscle growth and maintenance involve continuous cycles of protein synthesis and protein degradation, known as protein ____

Transcription

_____: DNA is transcribed into messenger RNA (mRNA) in the nucleus of the cell.

Translation

_____: The mRNA is transported to the cytoplasm, where ribosomes translate the mRNA into a specific protein sequence.

Post

___-translational Processing: After translation, proteins may undergo modifications (e.g., phosphorylation, glycosylation) to become fully functional.

targeted

Positioning and Localization: Once synthesized, the protein is ____ to the correct location within the muscle cell, whether it's part of the sarcomere (contractile unit of muscle fibers), in the sarcoplasm, or other parts of the cell.

degradation

Protein ____ (also known as proteolysis) is the breakdown of proteins into smaller polypeptides and individual amino acids. This process is critical for removing damaged or unnecessary proteins from muscle cells

Lysosomal

___- System: The lysosome is an organelle that contains enzymes capable of breaking down proteins.\

autophagy

It primarily degrades long-lived proteins and cellular structures, a process known as _____.

Calpain

____ System: _____ are calcium-dependent proteases that break down specific proteins within the muscle. This system is often involved in the turnover of proteins associated with the cytoskeleton, and it plays a role in muscle remodeling and adaptation to mechanical stress.

proteasome

Ubiquitin-Proteasome Pathway: This is the primary pathway for protein degradation in skeletal muscle. Proteins are tagged with ubiquitin, a small protein that marks them for destruction by the ___, a complex that breaks down proteins into small peptides and amino acids. This pathway is especially important for degrading short-lived and damaged proteins, and it is regulated by various signaling molecules and stress conditions.

hypertrophy

Muscle _____ (growth) occurs when the rate of protein synthesis exceeds the rate of protein degradation. This results in a net accumulation of muscle proteins, leading to an increase in muscle size and strength. Factors that promote protein synthesis (e.g., exercise, nutrition, hormones like insulin and growth hormone) are essential for muscle hypertrophy.

atrophy

Muscle ___ occurs when protein degradation exceeds synthesis, leading to a loss of muscle mass. This can happen during immobilization, malnutrition, aging, or disease. Atrophy is associated with an increase in the activation of protein degradation pathways, particularly the ubiquitin-proteasome system.

Hormonal

____ Regulation: Hormones like insulin, growth hormone, and testosterone can stimulate protein synthesis and muscle growth. On the other hand, cortisol (a stress hormone) can promote protein degradation and muscle breakdown.

Exercise

____: Resistance training and mechanical stress stimulate muscle protein synthesis. This is a key factor in muscle growth, as exercise-induced damage to muscle fibers leads to repair and subsequent hypertrophy

Nutritional

___- Factors: Adequate protein intake, particularly branched-chain amino acids (BCAAs) like leucine, is essential for stimulating muscle protein synthesis. Carbohydrates are also important to support recovery and protein synthesis after exercise.

protein

Increasing ___ intake, especially immediately post-exercise to promote recovery.

Inhibiting

____ protein degradation through the modulation of the ubiquitin-proteasome pathway or other proteolytic systems.

sarcoplasmic

The lysosomal system is responsible for approximately 25–30% of intracellular protein turnover, primarily degrading ____ proteins.

Lysosomes

____: These organelles contain a variety of hydrolytic enzymes that break down proteins into smaller peptides and amino acids.

Cathepsins

_____: A major family of non-specific proteases that function optimally in the acidic environment of lysosomes. They help degrade cellular components that are no longer needed.

Cystatin

____: An inhibitor of cysteine-lysosomal proteases, including cathepsins, which prevents excessive protein degradation.

calcium

The calpain system is a ____-dependent proteolytic system involved in muscle remodeling, myofibril disassembly, and meat tenderization postmortem. It consists of:

μ

__-Calpain

(Calpain 1): Requires micromolar (μM) levels of calcium for activation.

m

_-Calpain (Calpain 2): Requires millimolar (mM) calcium concentrations for activation.

3

Calpain _ (p94, skeletal muscle calpain): Specific to muscle and plays a role in myogenesis and myofibril assembly.

Calpastatin

______: A natural inhibitor of calpain activity, which is also calcium-dependent.

disassembly

• Responsible for myofibrillar _____, breaking down contractile proteins during muscle turnover.

proteolysis

Plays a major role in postmortem ____, which affects meat tenderness.

degrade

Despite its role in protein degradation, the calpain system does not fully ___ proteins into amino acids. Instead, it initiates breakdown by cleaving key structural proteins, allowing other proteolytic systems to complete degradation.

ATP

The ubiquitin-proteasome system is the primary pathway for degradation of short-lived regulatory proteins and damaged proteins in muscle. It requires ___ and functions through a sequence of enzymatic steps:

Ubiquitin

_____Activation (E1 enzyme): Activates ubiquitin, a small regulatory protein.

E2

Ubiquitin Conjugation ( ___ enzyme): Transfers ubiquitin to target proteins.

Attaches

Ubiquitin Ligation (E3 enzyme): _____ multiple ubiquitin molecules to the target protein (polyubiquitination).

26S

Once a protein is polyubiquitinated, it is recognized by the ___ proteasome, a large proteolytic complex, which degrades it into small peptides.

selective

Key Features of the Ubiquitin-Proteasome System:

• ATP-dependent process.

• Highly _____—only tagged proteins are degraded.

• Plays a crucial role in muscle atrophy, particularly during disuse, fasting, and disease conditions.

transcribe

Muscle cells ____ DNA into mRNA, which is translated into sarcomeric and non-sarcomeric proteins

positioned

Newly synthesized proteins must be ____ correctly within the myofibril to ensure proper muscle function.

post

The process involves ___-translational modifications that regulate protein stability and integration.

damaged

The ubiquitin-proteasome pathway plays a major role in degrading abnormal or ____ proteins, including actin and myosin.

disassembly

The calpain system helps with myofibrillar ____ to allow for remodeling.

lysosomal

The ____ system contributes to sarcoplasmic protein turnover and autophagy.

balance

Muscle cells ___ protein synthesis and degradation to adapt to exercise, injury, and metabolic stress.

exceeds

If synthesis ____ degradation, muscle hypertrophy occurs.

synthesis

If degradation exceeds ____, muscle atrophy results.

three

• The interaction between all ____ degradation pathways ensures proper recycling of proteins and prevents accumulation of abnormal or damaged proteins.