I love you Paleobird
(my sig is about you...)
I love you Paleobird
(my sig is about you...)
I had a cat named Phoenix until recently. I love you too Derpums.
Aw qt name for a kitty
A little primal gem - My Success Story
Weight lost in 4 months - 29kg (64 lbs)
Last edited by Neckhammer; 06-08-2013 at 08:11 AM.
You know I wonder if there as been any experiments aimed specifically at enhancing the placebo effect? Like a single blind trial with three arms placebo, placebo + doctor "letting it slip" that you are in the group getting the drug, and drug groups. Could be interesting to see how much we can maximize the placebo effect.
BTW thank you for your earlier post. I think you got some good things to say also. I agree opposite ends of the spectrum can be civil. It gets touchy when that word "optimal" gets employed by either side though. Like I said optimal is a fantasy for the most part (well there may be N=1 optimal, but even that is tricky) until someone with the genetic predisposition to live 95 years makes it to 116. Then we gotta document those facts. Till then its hypothesis vs hypothesis.
Last edited by Neckhammer; 06-08-2013 at 11:36 AM.
Let me address your argument, such as it is, piece by piece. I can't promise that I will be linear in my approach, but I'll attempt to at least be comprehensive.
You have to be careful when you get your knowledge from Wikipedia ... it may just lead to a superficial level of "understanding." With that said, your understanding of biochemistry is pretty mechanistic and you keep coming back with counts of the number of reaction steps involved in some metabolic pathway vs. another.
I've already pointed out to you that the number of steps in such reactions is something of a red herring. What is far more important is the rate of reaction, which is to say that a reaction chain comprising several very fast reactions may occur in less time than one consisting of a single, albeit relatively slow, reaction. To this end, I've asked you about the kinetics of the various enzymes involved in oxidizing pyruvate and fatty acids, something that you've cleverly ignored. What I was asking for was velocity vs. substrate concentration curves. I'm fairly certain that these won't be forthcoming, so we'll just move on.
Again, to reiterate, fats produce more ATP because they contain more carbon than glucose. Glucose is a 6 carbon molecule which metabolizes to two 3 carbon pyruvate molecules via a sequence of 10 reactions (!). Unlike pyruvate fats can be arbitrarily long but typically the predominant form in adipose tissue is palmitic acid, a 16 carbon saturated fat.
I was hoping to not have to do this, put you've forced my hand. This is how fatty acids enter a cell:
So after you've looked at that diagram for a while, I would like you to point to the endocytosis step. Now, obviously, should you accept my challenge, I can't see what you are pointing to. Of course, I don't need to, because there is no endocytosis step depicted. Fats don't enter cells, fatty acids do, and they certainly don't do so by endocytosis, which is why any discussion about insulin and its fat metabolism effects always center on hormone sensitive lipase and lipoprotein lipase, which are the enzymes which liberate fatty acids from adipose tissue, and the enzymes which liberate fatty acids from chylomicrons, respectively as precursors to their uptake or release from cells.
The reason I was hoping to not have to show the intricacies of cellular fatty acid uptake was because it is easy to get lost in the details. I ultimately went there because your understanding of things is rather odd, to put it mildly.
And now, we come to beta oxidation. By this point, those that have keeping score should not be too surprised to find out that you have it not just a little wrong, but rather, exactly backwards. Beta oxidation is a 4 reaction chain that produces acetyl CoA from fatty acids for entry into the citric / TCA / Krebs cycle. Now I could beat this dead horse until it is as mangled as your understanding of oxidation, but I really don't see the point, although I will show you a diagram of what I'm talking about ( the bit in the yellow box comprises beta oxidation, the end product of which is AcoA ):
Once you've formed acety CoA from you substrate, whether that is glucose, fats, or proteins, you have no chance of identifying which of those was the source at the level of the TCA cycle. It's just acetyl CoA, and we're off to the ATP generation races.
Glycolysis produces two pyruvate molecules from one glucose molecule, which in turn provide two acetyl CoA molecules, sufficient to drive the TCA cycle twice. Every time through the beta oxidation cycle, two carbons are cleaved off the fatty acid, which means that beta oxidation of 16 carbon palmitic acid will provide sufficient acetyl CoA to drive the TCA cycle 8 times. Or, in other words, one palmitic acid molecule provides roughly 4 times the ATP of a glucose molecule upon oxidation.
Each molecule of NADH+H and FADH2 that donates electrons to the electron transport chain winds up creating one H2O molecule. Each TCA cycle produces 3 NADH+H complexes, hence 3 molecules of H2O. So, each glucose molecule drives the TCA cycle twice, producing 6 H2O molecules. In addition, the conversion of pyruvate to ACoA by pyruvate dehydrogenase generates one NADH+H complex, and since we get two pyruvate molecules per glucose, the total H2O production from glucose oxidation in the ETC is 8 molecules.
Beta oxidation produces one NADH+H complex and one FADH2 per ACoA molecule generated, meaning that if you get your ACoA from beta oxidation rather than glycolysis, you generate ... how much additional water? Care to chime in here, Derp? According to you, it's a "huge amount." When I do the math, we get ... two additional molecules of H2O from the additional FADH2 yield. In case you missed it, that's a rather modest increase of 25%.
If at a cellular level, I have a requirement for, say, 120 ATP molecules, I can either oxidize 3 molecules of glucose, or 1 palmitic acid molecule. They both will yield the 120 ATP that I need, but the oxidation of the palmitic acid will also yield 25% more water. So ... assuming that I will concede that a 25% increase constitutes a "huge amount" of water, I wonder what a threefold increase in cellular water would constitute in your lexicon? Super duper ultra mega huge amount? What am I talking about? Well, if you recall, glucose and its metabolites are water soluble, which means that as they get sequstered or accumulate in a cell, they increase osmotic pressure, with the net result that water is driven into the cell. This is the by now well worn observation that for every gram of glycogen, you carry an additional 3-4 grams of water, the source of the miracle behind ketogenic diets, etc. etc. So, if we were playing water retention poker, at this point, I'd see your 25% and raise you 300%.
There is so much here that is so wrong that I could go on, if I weren't limited to 10000 characters in a single post. So, I'm just going to stop. It's a little like shooting fish in a barrel.