I see this claim in the (low carb) paleo community all the time but I've never seen any evidence of it. I've seen evidence that diabetes-induced hyperglycemia increases the generation of reactive oxygen species (ROS), but I've never seen anything that indicated that metabolizing lipids generates a different amount than metabolizing glucose. Since the actual mitochondrial oxidation of acetyl-CoA is the same for both, the difference must be during glycolysis that turns glucose into pyruvate or the step that turns pyruvate into acetyl-CoA.
So which is it? What part of the process generates more ROS? As far as I can tell, all the ROS that is generated during cellular respiration occurs during the electron transport chain, which would be the same for lipids or glucose. Is the claim actually that a fat-sourced acetyl-CoA molecule "burns cleaner" than a glucose-sourced one? If so, that's preposterous.
asked byTravis_Culp (39831)
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on November 02, 2011
at 11:25 PM
You are correct, the generation of ROS is in the ETC. But it differs from electrons derived from glucose or fatty acids. Glucose generates more NADH+, which then transfer electrons to complex I (NADH dehydrogenase). Fatty acids produce almost an equal amount of NADH+ and FADH2, which utilizes preferentially complex II (succinate dehydrogenase).
1 molecule of glucose:
Ratio NADH+:FADH2 = 5:1
1 molecule of palmitate:
Ratio NADH+:FADH2 = 2:1
Complex I is the main producer of ROS in the ETC, along with complex III. See:
Another complex which is utilized by catabolism of fatty acids is the electron-transferring flavoprotein.
A good, comprehensive review can be found here
And, the basics here.
on November 06, 2011
at 02:30 PM
You might find this paper interesting: How mitochondria produce reactive oxygen species
While there may be something to the balance of ROS formed from NADH, this is at least somewhat balanced, if not outweighed, by the fact that glucose doesn't produce byproducts that can hang around with inefficient oxidation to become peroxidized. Lipids do. Indeed there's really no "incomplete" glucose oxidation at the point of the mitochondria since up to pyruvate occurs in the cytosol whereas beta-oxidation of fatty acids occurs within the mitochondria.
ROS formation is also not necessarily detrimental, it plays an important signalling role. See, for example: Hydrogen peroxide: a Jekyll and Hyde signalling molecule
on November 03, 2011
at 01:22 PM
Nice Lucas. The paper you cited is in line with Rosedale:
Another implication of the hypothesis is that it may be possible to reverse age-related impairments by producing carefully controlled hypoglycemia at levels lower than can be produced by optimum dietary restriction.
This is also what T.Ely claims, vitamin C researcher, independently from Rosedale.
There are more things to consider.
Two modes of operation by isolated mitochondria result in significant O2?????? production, predominantly from complex I: (i) when the mitochondria are not making ATP and consequently have a high ??p (protonmotive force) and a reduced CoQ (coenzyme Q) pool; and (ii) when there is a high NADH/NAD+ ratio in the mitochondrial matrix.
... and eating fat provides more CoQ10.
But ROS might be good also, via mitohormesis
"Reactive oxygen species, derived from the mitochondrial electron transport system, may be necessary triggering elements for a sequence of events that result in benefits ranging from the transiently cytoprotective to organismal-level longevity"
but not if you are old enough http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2011.206623/full
The causes of this increased oxidative damage are uncertain, but substantial data now indicate that the ability of skeletal muscle from aged organisms to respond to an increase in ROS generation by increased expression of cytoprotective proteins through activation of redox-sensitive transcription factors is severely attenuated
So there are other things to consider, obviously, apart from glucose and fat
on February 21, 2015
at 01:19 PM
The question depends on more things.
That is not true because if cells use glycerol-3-phosphate shuttle, it will be ratio 2:1 (8 NADH, 4 FADH). And many cells can use this system - The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues
Palmitate creates NADH and FADH not only in Krebs cycle but also during B-oxidation and final ratio is almost 2:1 (31 NADH, 15 FADH). Lucas was right in this.
However, there is difference between ROS produced on complex II, glycerol-3-phosphate shuttle or ETF (fatty acids use this system).
Respiratory chain components involved in the glycerophosphate dehydrogenase-dependent ROS production by brown adipose tissue mitochondria:
The results showed that both substrates induced a similar ROS
production caused by the complex III but there was approximately
2.5-fold ROS generation associated with the dehydrogenase
in case of glycerophosphate compared to succinate.
So the question is difficult to answer. And it seems that ROS are not always bad
on November 06, 2011
at 11:35 PM
Beta-oxidation of fatty acids doesn't only occur in the mitochondria, thus it isn't the only place where ROS generation can occur with fatty acid metabolism. Peroxisomes another cellular organelle is involved in beta-oxidation as well. The organelle handles long chain fatty acids breaks them down with an enzyme(s) and shuttles them off to the mitochondria . During the FA breakdown ROS is generated. If you???ve ever had a really fatty meal it???s my opinion the warming effect is a consequence of this reaction.
Peroxisomes have another use especially in leukocytes where they can produce hydrogen peroxide to kill pathogens. They play a role in the liver as well. And their malfunction is speculated to be involved in many different inflammatory diseases.
I think they are a double edge sword, on one hand they generate ROS on the other hand they play a role against pathogens and can scavenge ROS, etc. However, things can go wrong. The circumstances in which things go wrong from what I???ve seen aren???t yet completely clear.
Peroxisomes is one place you won't find glucose metabolism :)