6

votes

Preferential Protein Catabolism? Chaperone-Mediated autophagy

Answered on August 19, 2014
Created September 10, 2010 at 2:56 PM

I've seen a rat study that alluded that when proteins were broken down, the muscles were taken last.

I've read opinion that stated that perhaps fasting is so health beneficial because of the bodies ability to choose "low use" proteins first. Thus eating up poorly constructed, weak or dying chains first, leaving the strongest to do their jobs, maybe even eating cancer etc

Anyone have opinions or better human studies that show and better explain this effect

D31a2a2d43191b15ca4a1c7ec7d03038

(4134)

on March 04, 2012
at 05:58 PM

Dr. Michael Eades discusses ketosis and CMA, in his blog post, "Ketosis cleans our cells": http://www.proteinpower.com/drmike/ketones-and-ketosis/ketosis-cleans-our-cells/ I'd like to ask Dr. Eades several questions about that post. :)

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on February 08, 2011
at 12:37 PM

The most likely way to get the body eliminate extraneous tissue is to do tabata sprints or metcon during a fasting period.

5de2fffda92c0bf2be7ede10cad55546

(1781)

on February 08, 2011
at 01:39 AM

*"Possibly fat storage cells that have been empty for a while could go as well"* Wouldn't that be great? CW at the moment says you can only add fat cells not remove them. Well, not without liposuction. ;)

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on February 07, 2011
at 10:39 PM

I think this method is also how i am mysteriously losing extra skin where i used to be much fatter.

3864f9a2af09b1b447c7963058650a34

(3703)

on September 18, 2010
at 03:06 PM

(clarify: by endurance I mean 'paleo' endurance -- low-mod intensity for longer durations v. HIIT)

3864f9a2af09b1b447c7963058650a34

(3703)

on September 18, 2010
at 05:33 AM

Rigorous, exhaustive exercise is excellent too... If you want to read more on BAT here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818667/pdf/nihms-164113.pdf

3864f9a2af09b1b447c7963058650a34

(3703)

on September 18, 2010
at 03:41 AM

Adam, Thanks esp for the 2nd link which I had access! There are several overweight yogi's I've met and I do believe they are healthier than me (at 18-20% body fat). Though fat may spill out hormones on the other hand the overall energy balance is the most important thing... and the mind can dictate that. Have you heard of brown fat? It's GOOD FAT. We can increase this like wild grapes and berries increase their own 'cellular antioxidants' with STRESSORS (e.g. cold showers, endurance exercise, heat shock/Bikram). I cannot prove, but I suspect yogi's have this.

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 14, 2010
at 04:21 PM

@ grace: You might want to check out Adipocyte Turnover http://dx.doi.org/10.1016/j.bbrc.2010.02.165 and Adipose Tissue as an Endocrine Organ Rexford S. Ahima http://liptepro.net/pdf/rsh_adipose_tissue_as_an_endocrine_organ.pdf - I both admire the elegance and am somewhat creeped out by the idea that a sufficiently large amount of adipose tissue on a given person can act as it's own endocrine organ, and get a big, fat vote in the control systems of the body.

3864f9a2af09b1b447c7963058650a34

(3703)

on September 12, 2010
at 09:07 PM

Oh. SO I think fasting is FINE! It is not an 'incomplete' protein, it's just no protein and it actually is a state of nutritional status which turns on PPAR (by being in ketosis), as long as one considers there are adrenals are BANGIN and not pooped out. Adequate sleep, rest and low mental stress augment the benefits of fasting.

D31a2a2d43191b15ca4a1c7ec7d03038

(4134)

on September 12, 2010
at 04:51 AM

Adam, this is why I jump on a rebounder. Thank you for the lovely explanation.

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 12, 2010
at 03:40 AM

Damaged cells, diseased cells, and the oldest cells that need replacing are the first to go. Possibly fat storage cells that have been empty for a while could go as well.

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 12, 2010
at 03:37 AM

I like the article you linked to for how it points out that a bodywide signal like the sustained presence of ketones can trigger an increase in the breakdown and reuse of damaged cells. I think this could be part of the joy of IF. Break down damaged cells while fasting, lay down brand new cells while feasting!

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 12, 2010
at 02:40 AM

The above processes can also just pick out damaged neurons or heart cells for replacement if cell signaling is working well, and avoiding sources of inflammation can help it work well.

4b97e3bb2ee4a9588783f5d56d687da1

(22913)

on September 11, 2010
at 11:38 AM

"damaged" cells, not the organ itself

62ed65f3596aa2f62fa1d58a0c09f8c3

(20807)

on September 11, 2010
at 03:38 AM

OK, good points, but the preferred proteins were supposed to be 'low use' and organs, etc, are not low use. I'd rather lose muscle! Steph, I would hope that cancer cells are not going to be abundant enough to supply much protein either. Ick!

1a8020e101199de55c1b3b726f342321

(1973)

on September 10, 2010
at 08:56 PM

Organs are full of protein, connective tissue as well.

4b97e3bb2ee4a9588783f5d56d687da1

(22913)

on September 10, 2010
at 05:29 PM

Cancer cells, bound protein on vascular walls, any non healthy non fat cell really...

62ed65f3596aa2f62fa1d58a0c09f8c3

(20807)

on September 10, 2010
at 04:26 PM

Kamal, exactly my question. I am confused as to where the protein will come from if not the muscles nor the diet. As far as I can tell, that stuff on my butt all seems to be fat.. ;-)

21fd060d0796fdb8a4a990441e08eae7

(24543)

on September 10, 2010
at 03:59 PM

This is a very cool question. My question though, is how much non-muscle non-essential protein is there to burn?

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4 Answers

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7
B3c62d89cd47b7d7209b6a99243d0ded

on September 12, 2010
at 02:36 AM

Ambimorph is correct on the autophagy front.

Recent studies have been showing that the body can be very good at knowing which individual cells are the most damaged, and it is becoming clearer, esp. in the case of mitophagy that the cell can locally consume damaged parts of a single cell and reform those components anew.

When cells are broken down, they are not immediately ejected (or excreted) from the body, they are the perfect building material for whatever new cells are needed. They are also in a ready state to be used a fuel.

A great free-to-read review on autophagy across many cell types is Nature. 2008 Feb 28;451(7182):1069-75. Autophagy fights disease through cellular self-digestion.

One of the items that I find extra applicable to my Primal Sprinting practice, is that brief metabolic stressing (Yay for brief sprints or metcon) seems to trigger the mitophagy (deconstruction) of the least efficient mitochondria in each stressed cell, followed immediately by the construction of copies of the more efficient mitochondria remaining in the cell... I think this is only one of the reasons why sprinting or quick metcon can have such rapid results for increased capacity.

D31a2a2d43191b15ca4a1c7ec7d03038

(4134)

on September 12, 2010
at 04:51 AM

Adam, this is why I jump on a rebounder. Thank you for the lovely explanation.

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 12, 2010
at 02:40 AM

The above processes can also just pick out damaged neurons or heart cells for replacement if cell signaling is working well, and avoiding sources of inflammation can help it work well.

5
100fd85230060e754fc13394eee6d6f1

(18706)

on September 10, 2010
at 09:55 PM

Maybe you are alluding at least in part to autophagy, the breaking up of damaged cells back into usable amino acids. Ketosis stimulates this, as shown here. I don't know how much protein this process will spare, though.

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 12, 2010
at 03:37 AM

I like the article you linked to for how it points out that a bodywide signal like the sustained presence of ketones can trigger an increase in the breakdown and reuse of damaged cells. I think this could be part of the joy of IF. Break down damaged cells while fasting, lay down brand new cells while feasting!

D31a2a2d43191b15ca4a1c7ec7d03038

(4134)

on March 04, 2012
at 05:58 PM

Dr. Michael Eades discusses ketosis and CMA, in his blog post, "Ketosis cleans our cells": http://www.proteinpower.com/drmike/ketones-and-ketosis/ketosis-cleans-our-cells/ I'd like to ask Dr. Eades several questions about that post. :)

3
3864f9a2af09b1b447c7963058650a34

(3703)

on September 12, 2010
at 09:03 PM

I love love LOVE this thread... I've wondered the same thing Stephen-Aegis...

Protein is such a coveted material in mammalian systems and nothing is wasted from the kidney and organ standpoint - all protein is re-filtered and recovered to prevent excretion. Kidney failure patients cannot retain protein -- and they are j*cked. In the environment, protein (meat/seafood) and omega-3 are relatively scarce and when humans learned to take advantage of these two, their brains emerged with consciousness, art, culture and global domination. Only the 'gut' can sense the abundance of protein and omega-3 in the environment (perhaps the sense of vision/smell in the brain) thus these receptors for amino acids and fatty acids (PPAR) control and regulate the instestines for the overall immunity and health.

Autophagy appears to me like recycling and I think the mitochondria very good at it, since they may be the most important generators of energy and regulators of systemic energy.

This may not address the core of your question but we lose protein and rebuild daily (during sleep...that's when we become BIONIC). If one wears a cast on the arm, the arm muscles will break down. Demand, genetics (myostatin) and perhaps diet control to what degree, I would imagine but I don't know for sure.

What I suspect is what the proteins someone consumes may have a bigger effect than we consider. Methionine -- apparently VERY CRITICAL to health, bowel immunity and antioxidant status. The studies below review it. The first gave a methione-deficient diet and quickly ruined the antioxidant status (glutathione) and gut lining (small instestinal villus atrophy, proliferative crypt cells, etc) and body weight gain decreased in neonatal pigs compared with controls.

Methionine is only find in meat, seafood and dairy in any meaningful amount. Beans and plants have almost none.

http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19293331/?tool=pubmed http://www.ncbi.nlm.nih.gov/pubmed/17143057

3864f9a2af09b1b447c7963058650a34

(3703)

on September 12, 2010
at 09:07 PM

Oh. SO I think fasting is FINE! It is not an 'incomplete' protein, it's just no protein and it actually is a state of nutritional status which turns on PPAR (by being in ketosis), as long as one considers there are adrenals are BANGIN and not pooped out. Adequate sleep, rest and low mental stress augment the benefits of fasting.

3864f9a2af09b1b447c7963058650a34

(3703)

on September 18, 2010
at 03:06 PM

(clarify: by endurance I mean 'paleo' endurance -- low-mod intensity for longer durations v. HIIT)

B3c62d89cd47b7d7209b6a99243d0ded

(10778)

on September 14, 2010
at 04:21 PM

@ grace: You might want to check out Adipocyte Turnover http://dx.doi.org/10.1016/j.bbrc.2010.02.165 and Adipose Tissue as an Endocrine Organ Rexford S. Ahima http://liptepro.net/pdf/rsh_adipose_tissue_as_an_endocrine_organ.pdf - I both admire the elegance and am somewhat creeped out by the idea that a sufficiently large amount of adipose tissue on a given person can act as it's own endocrine organ, and get a big, fat vote in the control systems of the body.

3864f9a2af09b1b447c7963058650a34

(3703)

on September 18, 2010
at 05:33 AM

Rigorous, exhaustive exercise is excellent too... If you want to read more on BAT here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818667/pdf/nihms-164113.pdf

3864f9a2af09b1b447c7963058650a34

(3703)

on September 18, 2010
at 03:41 AM

Adam, Thanks esp for the 2nd link which I had access! There are several overweight yogi's I've met and I do believe they are healthier than me (at 18-20% body fat). Though fat may spill out hormones on the other hand the overall energy balance is the most important thing... and the mind can dictate that. Have you heard of brown fat? It's GOOD FAT. We can increase this like wild grapes and berries increase their own 'cellular antioxidants' with STRESSORS (e.g. cold showers, endurance exercise, heat shock/Bikram). I cannot prove, but I suspect yogi's have this.

2
1a8020e101199de55c1b3b726f342321

(1973)

on September 10, 2010
at 08:55 PM

What you're describing is probably a very simplified version of what's happening. If you link the rat study you've described, we can go from there.

Protein synthesis and breakdown is a futile cycle, with both constantly happening at different rates. "Anabolism" is simply when the synthesis out paces the breakdown, and "catabolism" vice-versa.

It's likely the structures that are being degraded have defects or are undesirable for some reason, and the excess amino acids from that process serve to fuel the amino acid based GNG.

I have not reviewed any research on this subject, but burn victims would be a good place to start as there is quite a bit of literature on the catabolism they experience post trauma.

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