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Old 11-30-2008, 04:43 PM
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Default My summary of latest on Protein Metabolism

Solid article on protein metabolism was just released so I summarized its main points and added my commentary below!


Excellent Review on Protein Metabolism


http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Figures to refer to are below



Key points
In normal individuals following feeding there is an increase in protein synthesis / breakdown thats countered by a decrease in PS in the fasted state, overall there is no change in muscle mass. With resistance exercise which raises PS for up to 24 hours, there is net muscle tissue accretion (figure 1)

Effects of training
The unique element of resistance exercise is that unlike a meal skeletal muscle protein synthesis can be elevated for 24-72 hours. This suggests an “anabolic window” of opportunity in which any given bolus ingestion of amino acids during this time period should be preferentially used, or at least used at a higher rate by muscle. And data support this notion as ingestion of a protein source 24 hours after exercise increases muscle protein synthesis more than without the exercise stimulus.

Effects of training status
Now here are some interesting concepts. Basically training changes the way exercise effects protein turnover (figure 3).
1. Trained vs. untrained on the post exercise general muscle protein synthetic response
In this case an untrained individual can have an increase in protein synthesis for up to 48 hours. In contrast trained individuals have a greater increase in protein synthesis for the first 4 hours following exercise, but this declines to basal levels by 16 hours.
Of course my question is why is this the case, and anyone’s thoughts here would be great! My thoughts are that it may not simply be a factor of training status in and of itself that is changing our muscle tissues response in MPS to exercise, but rather the indirect effects of the ability of the muscle to resist damage. In other words for someone untrained any given stimulus is going to be enough to cause tremendous structural damage to the muscle and therefore elicit the need for greater more long term changes in protein balance to repair and remodel the damaged tissue. In contrast for any given stimulus in trained athletes the damage will be less and the need for remodeling and repair less. If true(and I think evidence supports this position) then it simply indicates the need for higher intensities and volume with training. But it also to me indicates the need again for more of a hypoxic stimulus, because again with training mechanical stimuli seem to lose there capacity turn on MPS, at least past 16 post training.

2. In untrained individuals there seems to be a general increase in all muscle proteins in response to both resistance exercise and aerobic exercise. In contrast in trained individuals after resistance exercise there is a preferential increase in muscle contractile proteins, while in endurance there is a preferential increase in mitochondrial based proteins.
I again suggest that what this indicates is that in those who are untrained, it is likely that both endurance and resistance exercise provide enough of a stimulus to both contractile and mitochondrial subfractions of protein to elicit an increase in PS in both of them. While in trained the need for higher order specific stimuli are needed to trigger these responses in each subfraction

Dose response of protein synthesis following exercise
I remember Gabe,Layne, and I watched Phillips present this data at ISSN. Basically they found that consuming 0, 5, 10, 20 or 40 grams of whey protein increase muscle protein synthesis in a dose dependent fashion up to 20 grams, but plataued thereafter, with a large increase in their oxidation thereafter. From this the authors suggested that 8-10 grams of essential amino acids(which is what the whey contained) or 20 grams of whey is sufficient and any more protein than this is a waste and willjust be oxidized or used as energy.

I recall during the presentation Layne, Gabe and I said this is faulty because it looks at one variable, protein synthesis. Layne raised his hand and stated
“ The problem with this data is that it assumes that amino acids prior to their oxidation are only used as substrate or to stimulate protein synthesis, in actuality they have many other signaling effects and may be converted to anabolic substances such as HMB which have secondary effects”

I agree with Layne. For example, take Leucine. Its effects on protein breakdown which was not reportd are maximized at at least double the amounts needed to maximize protein synthesis.
This is the problem also with looking at one variable to determine the effectiveness of any given dose of amino acids.

Protein source
As we are aware protein source effects growth. Their data for example showed that milk protein stimulated more growth than soy. Moreover their recent data demonstrates that whey stimulates greater protein synthesis than soy or casein,
This is excellent data, but we need to see a more complete picture by analyzing what occurs with protein breakdown in muscle.

Protein Timing
As we are well aware there is enough data to support the notion for immediate consumption of amino acids both immediately before and after exercise. Nothing new here

Insulin in the regulation of protein metabolism

Insulin has always had a controversial role in how it regulates protein metabolism, but the authors rightly point out the current consensus which is that insulin stimulates protein synthesis via its effects on PI3K signaling and inhibits protein breakdown, specifically via the Ubiquitin pathway(Ill discuss these in a bit).
I would point out also that insulins effects on protein synthesis are dependent on its capacity to increase blood flow by increasing nitric oxide production in the capillaries. This is one of the reasons why those who are insulin resistant may impair muscle growth, as they have poorer amino acid delivery to their muscle tissue following carbohydrate protein ingestion

Insulin after resistance exercise

Data suggest that when carbohydrates are administered alone after exercise, protein balance is improved by decreasing protein breakdown, but protein synthesis is not effected, overall the individual stays in negative protein balance or reaches zero protein balance. Now, what is most likely occurring is that by inhibiting protein breakdown, you actually inhibit available substrate needed to increase protein synthesis following training, which is why amino acids must be combined with insulin or carbohydrates.

Effects of aerobic exercise on muscle protein synthesis
Essentially moderately high endurance exercise (75% v02 max for 40 minutes) stimulates increases in mitochondrial, but not myofibrillar(contractile) protein synthesis

Cell signaling responses to resistance exercise and feeding

The authors point out that the pathways by which exercise and amino acids stimulate protein synthesis are converging . While I wont go into detail here, they point out that exercise activates PI3K-AKT-mTOR signaling to increase protein synthesis. What is not clear however is the time points for each response following training. For example recent data shows that mTOR signaling is back to normal 6 hours after training, while its downstream targets P70s6K are still elevated.

Intriguingly my lab at FSU is getting ready to elucidate a more detailed response of these pathways. To resistance exercise and link them to the exact protein expression as well.
I also want to point out that cell signaling is a real tricky subject as it does not always indicate changes in protein turnover. In Gabe and Laynes lab they are demonstrating this by showing that signaling proteins may be turned on while protein synthesis is not at particular time points

Effects of training status
10 weeks of training has been shown to heighten the sensitivity of anabolic signaling pathways to exercise such that they increase in activation more than in untrained individuals. What is not known is what happenes in highly trained individuals, but I suspect that there is less activation of signaling pathways in people highly trained to any given stimulus since as suggested protein synthesis is also lower.
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