Tuesday, March 19, 2013

Protons: Aside to T cells

Just because I like it. This is obscure. We can ignore the upper section as this is quite specific to T cells (which the paper is all about). What I love is the consideration that mitochondrial glycerol-3-phosphate dehydrogenase (marked as GPD2), sitting on the outer surface of the mitochondria, is very likely to be driving reverse electron flow through complex I to generate free radicals. Something I would avoid, personally (except perhaps in my T cells).



The bit I love is the big red outline arrow from QH2 going to the left towards complex I.

The whole mechanism and specific purpose here is linked to activation of the drive for T cells to divide, a free radical mediated phenomenon through NF-kappaB. What interests me at the moment is what might happen to a cell which cannot divide when mG3Pdh is driven, say by hyperglycaemia acting on a neuron... Lots of papers to wade through on this.

Peter

3 comments:

JoAnn Lennon said...

Nice blog..


Pure Edge Nutrition

Ellen said...

Peter, have you seen this paper?

http://www.lipidworld.com/content/9/1/79

Why would a meal of heavy whipping cream cause increase ROS?

Peter said...

Hi Ellen,

If you go back to 2000 you can look at Dandona's work on glucose and free radicals.

http://www.ncbi.nlm.nih.gov/pubmed/10946914

Much of his stuff on PMNs I have no time for and almost all of his interpretation I take my own slant on, but the bottom line is that all food generates TBARS. Casein possibly being an exception. And fructose too, possibly due to uric acid formation.

So I find the link you provide fascinating in that they have managed to show that glucose does not generate free radicals. This is, frankly, bollocks. Unless you use a controlled infusion of glucose which never exceeds metabolic needs you are BOUND to overdose, as happens when you eat a meal. Some degree of insulin resistance is then needed to limit caloric entrance to cells and this is always done using insulin resistance and this means superoxide, the spin off of which is hydrogen peroxide.

So either Bloomer et al or Dandona are wrong. Either incompetent or bent. I don't think it's Dandona.

Dandona found lots of TBARS immediately after cream ingestion, well before chylomicrons spiked.

http://www.ncbi.nlm.nih.gov/pubmed/11916766

He had no real explanation for this, mostly because he was not measuring FFAs. Cream generates a lot of palmitic acid. A fair chunk will be as FFAs. When FFAs are available to provide calories, cells no longer need glucose. How do they say no? With insulin resistance, ie superoxide, the spin off of which is hydrogen peroxide. Palmitate generates superoxide. If you live in a country saturated with PUFA the normal signal used to balance cellular energy entry results in TBARS. That's probably bad, but if you live on soya oil, that's your problem.

The other huge error is the assumption that hydrogen peroxide is Badness Incarnate. This is the level of lack of comprehension which suggests that antioxidants are a Good Thing. A sentiment not born out by any intervention trials, usually the opposite is found. Free radicals are signals. Use them or die.

I happen to like superoxide, it keeps me alive. I've not much against H2O2 either. It's one way mitochondria speak to the nucleus. Communication is good, so long as you say useful things.

Peter