Introduction molecular exercise physiology - L2 Flashcards
What happens to muscle mass as a result of high levels of inflammation?
It promotes breakdown of muscle mass
What is the difference between catabolism and anabolism?
Catabolism is the breakdown aspect of metabolism, whereas anabolism is the building-up aspect.
Which pathway is important for protein synthesis?
mTOR pathway
Describe the ATP-phosphocreatine system.
- The system produces energy for muscle contraction via the release/production of ATP.
- When ATP loses a phosphate (out of 3) energy is released and ATP is converted to ADP.
- Vice versa, when ADP gains a phosphate, it is converted back into ATP to store energy.
- Phosphocreatine is also stored in muscles and is able to add its phosphate to ADP.
- Creatine kinase is responsible for releasing the phosphate molecule from phosphocreatine so that the phosphate can be added to ADP and stored as ATP.
How can ATP concentration stay constant while AMP and ADP increase during aerobic exercise?
- As explained in card 4, ATP is converted to ADP when there is an energy demand for muscle contraction.
- Sometimes, ADP is further broken down into AMP as it donates its second phosphate molecule to give (extra) energy for cellular activitities.
- During aerobic exercise, ATP is converted into ADP and/or AMP. When ATP levels decrease and AMP levels increase, AMP binds to AMPK (AMP-activated kinase), which leads to the activation of AMPK (through phosphorylation) in order to activate processes such as activation of catabolic pathways and inhibition of anabolic pathways to regenerate ATP.
Besides AMP, another kinase can also activate AMPK for regeneration of ATP. What kinase is this?
Ca2+/calmodulin - dependent protein kinase kinase-beta (CaMKKβ). This kinase activates AMPK by phosphorylation of their activation-loop Thr residues in response to increasing intracellular Ca2+ concentration
What processes are associated with AMPK activation?
- Mitochondrial biogenesis
- Angiogenesis
Calcium and AMPK activation stimulate the expression of Peroxisome proliferator-activated receptor-γ (PPAR-γ). Describe this pathway and what the result is of the activation of this pathway.
PPAR-γ is a nuclear receptor that is activated when PGC-1a (PPAR-y coactivator-1alpha) interacts with PPAR-γ. This complex activates the transcription of various genes, most importantly:
- the complex activates the transcription factor Nrf1 resulting in the translation of genes related to mitochondrial biogenesis and oxidative metabolism.
- the complex interacts with Mef2 and Nfat, two transcription factors involved in the gene expression of type I myofibers.
Mef2 and Nfat can also be activated independently of PPAR-γ-PGC-1a complex activation. How?
With the use of Ca2+ calcineurin or CaM kinases
How does endurance training stimulate the biosynthesis of mitochondria?
During (endurance) exercise, your muscles contract repeatedly. Muscles contract as a result of the activation of the sarcoplasmic reticulum (SR) by ATP. Activation of the SR results in the release of Ca2+, which serves as an intracellular messenger molecule for the activation of calcineurin, CaMKII and p-AMPK. These molecules activate other molecules like PGC-1a, COX and citrate synthase (also Mef2 and Nfat), resulting in the biosynthesis of mitochondria.
What relationship exists between the number of nuclei per mm muscle fiber length and the total fiber cross-sectional area (FCSA)?
The amount of nuclei/mm fiber length is associated with the amount of FCSA. So a high number of nuclei/mm fiber length = a high total of FCSA.
What are satellite cells?
Multipotent cells found in mature muscles. They are precursors of skeletal muscle cells. Normally, they are in their native, quiescent state (i.e. not dividing/differentiating). But when muscle tissue is damaged due to injury or exercise, satellite cells become activated, which leads to proliferation and differentiation into myoblasts (muscle precursor cells capable of fusing to form new muscle fibers or repairing damaged ones).
The following molecules are involved in mechanosensation. Explain in short their primary function in mechanosensation.
- Dystrophin-associated glycoprotein complex
- Costameres
- Focal Adhesion Kinase (FAK)
- Calcium
- Phospholipid cleaving enzyme phospholipase D (PLD)
- Dystrophin-associated glycoprotein complex (DAGC): complex found in muscle cells that connects cytoskeleton to extracellular matrix -> role in maintaining structural integrity of muscle fibers.
- Costameres: located at Z-lines of muscle cells, play a role in transmitting mechanical forces between cytoskeleton and ECM.
- Focal Adhesion Kinase (FAK): activated in response to mechanical forces and plays a role in signal transduction of pathways for cell adhesion and mechanotransduction.
- Calcium: mechanical forces can lead to intracellular calcium level changes, which can trigger various cellular responses, such as muscle contraction.
- Phospholipid cleaving enzyme phospholipase D (PLD): enzyme that cleaves phospholipids to generate lipid second messengers.
Explain why there is time-dependent activation of mTOR (in the context of exercise).
- Pre-exercise: basal level of mTOR activity
- During-exercise: muscle cells experience mechanical stress/load and damage, which triggers growth factors such as insulin-like growth factor 1 (IGF-1) and the activation of mTOR.
- Post-exercise: mTOR activation may increase in the hours following exercise, because mTOR is essential for muscle repair, growth and adaptation.
What are reactive oxygen and nitrogen species (RONS)?
RONS are molecules containing oxygen or nitrogren atoms that are produced during various processes (metabolism, UV light, radiation, smoking, air pollution, inflammation) capable of causing DNA or protein damage.
