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Insulin pathway breakdown
- Insulin binds to: Insulin receptor (IR)
- IR binds
How does Protein Kinase C lead to INCReased Protein synthesis?
Via INCREASE in Ca release
How does muscle fiber help dictate size of muscle?
- The more FAST Twitch muscle fibers: Greater amt of APs (Increased ACh release) so Ca release is INCREASED during min. contraction vs slow twitch
- This means that doing similar exercise, fast twitch is releasing more Ca, therefore leading to: INCREASED PROTEIN Kinase C
- Since Protein Kinase C is activated by Ca: More Calcium = more protein kinase C = more muscle growth
Roles of inulin (AND other growth hormones)
- 1: ENHANCE protein synthesis (ie activate protein kinase c, lead to increased prot synth)
- 2: Activate GLUCOSE Transport
- Also, insulin can activate: AKT
5 MAJOR STPathways involved in REGULATION of Growth and development
- These are necessary for maintaining and enhancing cell fxn
- 1. PI3K/AKT
- 2. p38-MAPK
- 3. JNK-MAPk
- 4. ERK-MAPK
- 5. NF-kB
Pathway activation in each cell..different or same?
Each cell has a different ARRAY of PROTEINS produced: Constantly changing due to ALTERED Activation of different TFs
2 outcomes of mRNA
- 1: Translation by the ribosomes
- 2: Degradation by RNases
- Transcription is HEAVILY REGULATED: Need enough mRNA to not all get degraded, enough so some can still get translated
How is PROTEIN Synthesis regulated
Via Transcriptional regulation: DONE VIA ST PAthways
To activate protein synthesis
- Ca alone can do this via Activating ST pathways
- Insulin can do this, but not needed
- Protein kinase C: which is activated by Ca
How do you release the most Ca while exercising
- 1. Intensity: Maximum intensity releases MAXIMUM amt of Ca, activating Maximum ST Pathways
- 2. Duration: Longer Time periods of Less than MAX to get same Ca release as at MAX
End results of 30% Max workout (increased intensity and duration)
- Long duration: Leads to INCREASED Radical production (ROS) and increased Ca vs shorter timepoint.
- Increased intensity: Releases More Ca, leading to Increased ST Pathway activity and increases in protein synthesis
- RESULT: Hypertrophy due to Calcium and oxidants
Phospholipase A2 (PLA2)
- Activated by Protein Kinase c, which is activated by Ca
- Further activated by ERK/MAPK, p38/MAPK
- INITIATES Pro-Inflammatory RESPONSE
What initiates Pro-inflammatory response
Mild Metabolic STRESS (Normal met fxns during exercise): DAMAGE NOT NECESSARY to initiate pro-inflamm response
Increased activation of ST pathways leads to..
- Increased pro-inflammatory responses: NFkB activation to get IL1, IL6(anti-inflamm) activation (NOT TNF-alpha...this is indicating damage, not stress response)
- Increased H2O2 production
- Increased Radical production
Why is duration of exercise important for proteiin synthesis
- Need Long time of stress to activate and allow for production and binding of growth factors
- Insulin grown factor: needs to be first ACTIVATED, then PRODUCED...takes time for this
WHAT Proteins necessary for HYPERTROPHY?
- Groth hormones
- ERK: Jun+Fos need to combine with STATS to allow for INCREASED TFs to increase MYC, p21 SYNTHESIS
- Leads to: Proliferation of satellite cells and fusion of these with existing muscle cells.
- To INCREASE CELL DIVISION of stem cells (which ultimatey become muscle cells): PROSTOGLANDIN needs to be activated
To increase MITOCHONDRIAL BIOGENESIS
- Increased Calcium and AMP (activate CaMK and AMP-PK): activate MEF2 and NRF1
- Meanwhile: CREB and ATF2 (activated by PI3K/MAPK pathways) activate PGCI1
- Combining PGC1a with MEF2 AND NRF1: Activates SYNTHESIS of TFAM
- Once enough TFAM is generated: Transports to mitochondria..for MITOCHONDRIAL BIOGENESIS
- **DURATION IS KEY HERE! Lots of PROTEINS have to get SYNTHESIZED and travel
Increasing what leads to Increased performance?
- 1: HYPERTROPHY (ie 30%max increases prot. synth)
- 2: Mitochondrial Biogenesis (ie HIIT training)
- 3: CELL DIVISION!
- Anyway to Activate ST pathways the most for a LONG Duration until you can't do anymore