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Hyperlipid
You need to get calories from somewhere, should it be from carbohydrate or fat?
Wednesday, August 02, 2017
Metformin (02) The dose makes the poison
Before the days of interest in metformin as an anti-neoplastic agent, a performance enhancing drug or a longevity promoter, it was just given to T2DM patients to help lower blood glucose levels. These folks, as a group, quite often have significant renal disease. Which can render metformin and lactate cumulative in the blood stream and lead to a life threatening lactic acidosis.
This paper looked at a series of 10 hapless folk to whom this happened:
Metformin overdose causes platelet mitochondrial dysfunction in humans
The mean blood concentration which gets you an ITU bed was 32mg/l. Now this is a clinical paper, written by clinicians. Nothing wrong with that, except they use Noddy units which makes the metformin concentrations extremely difficult to relate to the vast body of metformin research, which uses units of millimolar or micromolar.
So we really need to take this image
and think of it in these terms when we're looking at research papers using mmol or micromol concentrations:
Bear in mind that these are very chronic exposure values and metformin is thought to be progressively cumulative within the mitochondria on chronic exposure. Of course, complex I is intra mitochondrial and there will be some dependency on cumulation in getting significant effects at this site. What we can say is that, in the above diagram, there is not enough inhibition of complex I to raise lactate production in platelets, an extra-hepatic tissue (hepatocytes may be slightly different), unless we are using near-death concentrations.
What is not hidden away inside the mitochondrial matrix is mtG3Pdh. It's on the outer surface of the inner mitochondrial membrane and will be exposed to whatever metformin concentration that manages to get inside the cell.
From the classic paper
Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase
we have this graph from Figure 3, using a slurry of mashed up mitochondria and some glycerol phosphate:
Here we have a significant effect on the oxidation of glycerol-3-phosphate at micromolar concentrations. Admittedly by 50渭mol we are looking at very much the upper end of therapeutic concentrations but an effect is clearly visible at this level. We can say from the platelet paper that exposure to 250渭mol (black circles at the bottom of the graph), if sustained, will put you in the ITU with potentially fatal lactic acidosis.
Because mtG3Pdh is exposed to cytoplasmic (non cumulative vs mitochondrial) metformin levels it will see the drug at plasma concentrations (or slightly less) and it will see these concentrations as soon as metformin enters the blood stream.
If you want a performance enhancing drug for endurance exercise, say a cycle race taking about three hours, you can pop a single metformin 500mg tablet one hour before the start of the race and extend your time to exhaustion from 167 minutes to 191 minutes. That might make some difference to winning vs not finishing.
Metformin improves performance in high-intensity exercise, but not anaerobic capacity in healthy male subjects
Equally, there is no acute effect on lactate levels in the same study. This is no surprise as I find it difficult to envisage acute complex I blockade, to lactate generating levels, as a performance enhancing ploy.
TLDR: metformin probably works in the cytolasm on mtG3Pdh. Rising lactate may well indicate mitochondrial cumulation and some degree of complex I inhibition. Extrapolating benefits from studies based around millimolar concentrations in-vitro may well put you in to the ITU if you try them in-vivo.
Peter
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Wednesday, August 02, 2017
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Metformin (02) The dose makes the poison
Tuesday, July 25, 2017
Metformin (01) Insulin
This image is taken from the paper Insulin requirement for the antihyperglycaemic effect of metformin and it deserves a little consideration.
They are using BB/S rats which spontaneously develop T1DM if fed standard rodent chow. In the absence of exogenous insulin they die but giving them a little Ultratard twice daily keeps them alive for quite some time. Stopping the Ultratard allows exogenous insulin withdrawal to produce an acute, alive, an-insulinaemic rodent model. This is the model used and at the start of this experiment the rats had no detectable insulin in their blood.
At time point -60 these an-insulinaemic rats were given metformin intrajejunally. Over the next 60 minutes the metformin did nothing to lower plasma glucose. At time point zero they were given a small intravenous bolus of glucose. Metformin had no effect on the additional hyperglycaemia induced.
At time point +90 they were given neutral insulin intravenously. In the control group plasma glucose concentration dropped to a nadir of 20mmol/l at time point +150 but in the metformin treated rats the same dose of insulin continued to reduce the plasma glucose to 10mmol/l at time point +180, when p dropped below 0.05.
So.
Insulin is essential to demonstrate any effect of metformin on blood glucose.
Any idea about how metformin works, be that via the inhibition of mtG3Pdh or via inhibition of complex I, has to accommodate the essentiality of insulin.
That's an interesting constraint.
Peter
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Tuesday, July 25, 2017
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Metformin (01) Insulin
Monday, July 24, 2017
An update
Hi All.
We've moved house. It has not been the simplest of moves. OK, it was awful. However it was also worth it as we live here now.
While the house is in pretty good order the acre and a half of ground needs some TLC before we can get the chickens strip grazing and maybe some stock in, so I sort of doubt there will be a huge amount of free time to blog. Maybe a little musing on metformin might be possible...
Anyway, we're alive and busy and now live some distance from the nearest main road (in Norfolk terms).
Peter
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Monday, July 24, 2017
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Saturday, June 03, 2017
Why stop at formaldehyde?
If we consider the dissociation of hydrogen:
the right hand side of the equation can supply electrons to another reaction. The tendency for this to occur is in part dependent on the pH of the solution. If we consider alkaline hydrothermal vents we have a pH of around 11, this drives the reaction to the right because the protons avidly combine with hydroxyl ions to give water:
Which means that there is a marked tendency to supply electrons for any electron-accepting reaction. The electrons can hop on to an FeS barrier (each changing the charge on an Fe from 3+ to 2+) which separates the vent fluid from CO2 rich, acidic oceanic water:
Deriving from fluid with a pH of 11 these electrons have a redox potential of -650mV, ie they are highly reducing.
If we now look at the situation on the oceanic side of the barrier we have:
and by adding on the factor of an acidic pH, with lots of protons driving the reaction to the right we have this:
Under these conditions electrons supplied at -650mV are very able to allow the reaction to proceed to the right yielding CO. Repeating the process yields CH2O and metabolism is on its way.
OK. Nick Lane makes these points in his paper:
1. There is no contact between the H2 in the vent fluid and the CO2 in the ocean fluid. The two Hs in the formaldehyde come from oceanic protons combining with vent H2 derived electrons.
2. I've shown the reaction occurring once to CO and again to CH2O. Why stop at twice? Given a supply of -650mV electrons why not keep generating CO and inserting it, along with e- and H+, in to whatever hydrocarbon you have already got in the vent fluid? Nick Lane has reaction sketches for generating almost all of the Krebs cycle components on this basis.
Theoretically, if you wanted to make an origin of life reactor to test whether you can generate a multitude of the hydrocarbons at the core of metabolism you don't actually need a supply of alkaline hydrogen rich fluid. This only supplies electrons at -650mV. An alternative supply would be a 1.5 volt battery with some sort of voltage reduction to get from -1500mV to -650mv and you're away.
A microporous FeS electrode in Perrier water, energised by an AA battery via a couple of resistors and you might just be set up. Getting the apparatus anoxic and detecting the products might be more of a challenge!
Edit Finally followed Nick Lane's final reference. These folks have reached pyruvate via an energised FeS electrode. It's a lot more complex than Perrier water but it works. End edit
Peter
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Life (18) Why stop at formaldehyde?
Thursday, June 01, 2017
Nick Lane on Proto-Ech
Nick Lane has a few more downloadable papers available on his website, two of which focus on ideas I've thought a lot about. Here are a few quotes:
Iron Catalysis at the Origin of Life
"Why does the reduction of ferredoxin via Ech depend on the proton-motive force? The answer is as yet unknown, but cannot relate to reverse electron flow [as originally proposed (49)] as these methanogens do not possess an electron-transport chain (37,38). A more pleasing possibility is that pH modulates reduction potential at the active site of the enzyme. The flux of protons through Ech from the relatively acidic exterior could lower the pH at the active site of the enzyme, which should facilitate reductions that depend on protons, including CO2 as well as some ferredoxins (50)".
My italics. Next:
Proton gradients at the origin of life
Aside: If you read the full text of Lane's paper you will take note of Jackson JB (2016) Natural pH gradients in hydrothermal alkali vents were unlikely to have played a role in the origin of life. And this passed scrutineering. Nick Lane does not seem impressed. End aside.
"One possibility is that prebiotic carbon and energy metabolism entailed the synthesis of reactive thioesters analogous to acetyl CoA, such as methyl thioacetate, coupled to substrate-level phosphorylation, generating acetyl phosphate and ultimately ATP [1, 17, 27, 60 #8211;63] as still happens in bacteria [14, 31]".
"Across the barrier, in acidic conditions, CO2 is more easily reduced, and so is more likely to be reduced by Fe2+ in the barrier. The semiconducting barrier should transfer electrons from Fe2+ on the alkaline side to Fe3+ on the acidic side. The thickness of the barrier does not matter, so long as it is semiconducting. The two phases do not come into direct contact - H2 and CO2 do not react directly (Fig. 3)".
This is really neat, it puts in to a published paper many of the logical concepts that went in to the Life series. I really like the pre biotic ideas of electron transfer across any-thickness FeS barriers. No need for membranes, indeed insulating "crud" membranes would hinder electron transfer from the FeS wall to the enzyme, necessitating the generation of a pore like structure (ancestor to NuoH) to get the voltage generating acidic pH to the active enzyme's site.
This ferredoxin reduction plus subsequent substrate-level phosphorylation is where it should all start. NuoH starts as a pH channel, not part of a nano machine. That comes later with reversal of proton flow and the development of complex I, a true advanced nano machine.
I still don't buy ATP synthase (another very complex nano machine) as running on the primordial vent proton gradient as Nick Lane holds to. Later developing Na+ energetics look much more likely, these following on from Proto-Ech's pore duplication to form a Na+/H+ antiporter, giving a usable Na+ gradient. That clearly post-dates some sort of membrane, which ferredoxin based metabolism must precede when using a geochemical proton gradient. NuoH becomes essential only after a crude membrane forms to impede this process of ferredoxin reduction.
Nice papers.
Peter
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Thursday, June 01, 2017
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Life (17) Nick Lane on Proto-Ech
Tuesday, May 30, 2017
Adrian Ballinger on Everest
Back at the end of 2015 Mike Brampton and I had a conversation about climbing Everest.
Based on Graph A from Fig 3 in D'Agostino's rat paper
Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats
our conclusion was that summiting Everest might be best achieved using a ketogenic diet. I know nothing about extreme climbing or the culture which goes with it but it came as no surprise, via Mike, that they carb loaded and carb loaded and carb loaded. You know, sugar has its own partial oxygen supply built in to the molecule. No point trying to burn fat if there's no oxygen*. Understandable but, obviously, completely incorrect. I think Mike had been trying (frustratedly) to convert altitude folks to fat centred thinking for some years before this.
*It's true that there is no point trying to burn fat under anoxia. But given some oxygen ketosis pays dividends.
So it was interesting to pick up this link on Facebook:
How Adrian Ballinger Summited Everest Without Oxygen
This fits in with Veech's concept of increased metabolic efficiency per unit O2 consumed when burning ketones and D'Agostino's discovery of an "unexpected" rise in arterial PO2 in rats gavaged with a betahydroxybutyrate/acetoacetate combination precursor, while they were breathing room air (PaO2 from 100mmHg to 130mmHg, pardon the archaic units).
Very gratifying, even if completely different from the approach taken by Naked Mole Rats and their fructolysis.
Peter
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Tuesday, May 30, 2017
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Adrian Ballinger on Everest
Fructose and lactic acid in Naked Mole Rats
Naked Mole Rats appear to use fructose as their preferred metabolic substrate when exposed to both physiological hypoxia (which is common in their lifestyle) or complete anoxia under experimental conditions. It's irresistible to go and find out a little about why they might do this.
Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat
I suppose the first thing to say is that the fact that fructose is protective against hypoxic cellular injury has been known for a long time, this paper coms from 1992:
Fructose protects rat hepatocytes from anoxic injury. Effect on intracellular ATP, Ca2+i, Mg2+i, Na+i, and pHi
There was a lot of work done in the 1980s and 90s looking at ways of preserving liver cells under anoxia. I'd guess this was looking to improve the survival of harvested livers within the transplant program.
If we look at ATP levels compared to an externally supplied control (MDPA) we have this graph, with hypoxia imposed at one hour and relieved at three hours:
ATP falls faster within the first 30 minutes of anoxia with fructose. Although the trends are interesting, all else is ns after 45 minutes. So fructose causes a more severe ATP depletion than glucose. However a better marker is the ratio of ATP to Pi (phosphorylation potential), here plotted as the inverse for some reason, ie the lower the better in the graph:
So under fructose there is less ATP in the cytoplasm than under glucose but the phosphate level is even lower, giving a similar or more favourable ratio of ATP to Pi except at the 30 minute mark. So the next question is: Where has the phosphate gone?
This might be related to the protective effect of cytoplasmic acidosis. It doesn't seem to matter how you acidify the cytoplasm (fructose is as good a way as any), it's the acidosis which appears to protect against mitochondrial failure. There's a nice paper here
Protection by acidotic pH and fructose against lethal injury to rat hepatocytes from mitochondrial inhibitors, ionophores and oxidant chemicals
and here
Intracellular acidosis protects cultured hepatocytes from the toxic consequences of a loss of mitochondrial energization
So if we go back to Gasbarrini's paper we can look at a surrogate for intracellular pH and how it differs between fructose and glucose:
Fructose produces a much more profound acidosis. If we look at that basic ETC doodle I used in the rho zero cell post, but eliminate complexes I, II, III and IV we have this:
We have here two process which can be driven by an excess of protons in the cytoplasm over those in the mitochondrial matrix. Transport of Pi in to the mitochondria and synthesis of ATP. Which of these is most important to ensure cell survival is hard to say. It is even quite possible that it's neither and that maintaining an excess of protons outside the mitochondria maintains delta psi so defers the commitment to apoptosis or the occurrence of necrosis.
Later changes which confirm the commitment to cell death are an influx of extracellular calcium in to the cytoiplasm. This is marked under glucose and stays within tolerable limits with fructose. I strongly suspect the metabolic decision making is being controlled by the pH drop and the Ca2+ influx is consequent to a mitochondrial decision as to how badly damaged the cell might be. But it's hard to be sure with the data we have in these rather elderly papers.
About that acidosis:
Here are the reactions relevant to the pH change in lactic acidosis, all taken from the wiki entry on lactic acid. They are interesting. This is the situation down to pyruvate:
There are two protons generated to acidify the cytoplasm. Now look at this step where pyruvate is converted to lactate. The molecules in the red oval are needed to form the lactate.
So where did the two acidifying protons go to? They are consumed in converting pyruvate to lactate. Does lactic acid generation actually acidify the cytoplasm? It appears not to do so here but it must do because the overall reaction is:
So where are these two protons? They are in the two ATP molecules:
The conversion of ATP to ADP releases them. So lactate causes acidosis only when the ATP generated during glycolysis/fructolysis is consumed... Obviously ATP depletion is common in anaerobic exercise or hypoxia/anoxia. Hence lactic acidosis shows under these two conditions.
The Naked Mole Rat paper is very descriptive, with lots of experimental results but is light on insight as to hows and whys. I think the above scenario might well have explanatory power and might have been extended from the liver to the rest of the body in NMRs.
Peter
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Tuesday, May 30, 2017
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Fructose and lactic acid in Naked Mole Rats
Thursday, May 18, 2017
Fructose and metabolic syndrome: Uric acid
Some weeks ago a friend sent me a full text copy of the Naked Mole Rats (NMR) paper
Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat
which demonstrated that they (NMRs) appear to generate and use fructose as a coping stratagem for dealing with hypoxia or even anoxia. This is fascinating and leads back to research in the late 1980s, mostly looking at anoxia in liver or liver cells. I'm guessing that this liver work was funded to look at ways of improving the condition of transplant grafts. Fructose is significantly better than glucose for supporting anoxic liver cells, possibly something you might expect, possibly not. Perhaps in another post.
Anyway. So I've been looking at why fructose is different to glucose and to do this you end up asking rather difficult questions about the upper sections of both glycolysis and fructolysis.
Fructose enters the fructolytic pathway by being phosphorylated very rapidly to fructose-1-phosphate. Given a large enough supply of fructose this phosphorylation can deplete the ATP supply in a cell, most obviously in hepatocytes which bear the brunt of metabolising fructose. This takes place before aldolase generates the trioses which probably (or don't, in the case of fructose) control insulin signalling through mtG3Pdh and the glycerophosphate shuttle.
If this initial ATP depletion by fructokinase is profound it is perfectly possible to take two "waste" ADP molecules and transfer a phosphate from one to the other. This generates one ATP and one AMP. The ATP is useful to the cell and the excess AMP is degraded to uric acid.
This is all basic biochemistry.
In the Protons series I have worked on the (incorrect) basis that fructose should drive the glycerophosphate shuttle hard enough to generate RET (reverse electron transport) and so signal insulin resistance. The degree of insulin resistance should neatly reduce insulin mediated glucose supply by an appropriate amount to offset the fructose and so maintain a stable flux of ATP generation from the combined fructose and glucose. That's not quite how it appears to work. Even before the aldolase step in fructolysis, the body is starting to prepare the process of insulin resistance. This paper is not unique but shows general principles:
Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver
The title of the paper is sneaky, it doesn't give away the answer! Nor does the abstract. If you don't want to read the paper, the missing link is NOX4.
NADPH oxidase 4 (NOX4), if exposed to uric acid (present here from fructolysis induced AMP degradation), translocates to the mitochondria and starts to generate enough hydrogen peroxide* to down regulate aconitase, abort the TCA and divert citrate out of the mitochondria through the citrate/malate shuttle for DNL. This will not just affect fructose metabolism, acetyl-CoA from glucose, entering the TCA as citrate, will also be diverted to DNL.
*The NOX family appear to be the only enzymes with no function other than to produce ROS, mostly superoxide. NOX4 is unique in that it always produces hydrogen peroxide. There is uncertainty if the "E loop" of the enzyme converts superoxide to hydrogen peroxide directly or if this is a docking site for superoxide dismutase, which does the conversion as an accessory module to NOX4.
I think it is a reasonable assumption that the hydrogen peroxide generated by NOX4 will be what signals the insulin resistance induced by fructose, rather than RET via mtG3Pdh. Quite why fructose doesn't drive the glycerophosphate shuttle is a difficult question to answer. Obviously the aldolase products of fructose-1-P (fructolysis) differ from those of fructose-1-6-bisphosphate (glycolysis) but these pathways are very difficult to get at experimentally and I've not found any papers looking at what controls why dihydroxyacetone phosphate from fructolysis doesn't drive mtG3Pdh, but that appears to be the case. There are hints that some activation of the glycerophosphate shuttle does occur but NOX4 seems to be the main player. It might relate to the consumption of NADH in the conversion of glyceradehyde to glycerol and so reducing the need to decrease it using the glycerophosphate shuttle. Hard to be sure.
So. Uric acid is the evil molecular link between fructose and metabolic syndrome via NOX4. And yes, yes, you can block metabolic syndrome using allopurinol to reduce uric acid production in rats but you have to give them a sh*tload of it. After that NOX4 might be considered evil or hydrogen peroxide is evil or aconitase is evil when it's on strike. Lots of drug targets available for molecular cleansing.
My own concept is that there is the necessity to developing insulin resistance when fructose is available so as to limit glucose ingress to offset the ATP from that fructose ingress. If that is done by NOX4, so be it. The facility to deal with fructose by the generation of hydrogen peroxide is not random, it's not some accidental mistake perpetrated by evolution on hapless humans who munched on a few Crab apples or found a little honey. It is an appropriate evolutionarily response to a relatively common occurrence. The fact that uric acid mediated insulin resistance is common to alcohol metabolism as well as to fructose metabolism suggests that this mechanism is a general approach to dealing with a calorie input which takes priority over metabolising glucose.
Developing a drug along the lines of allopurinol to block uric acid production, or an inhibitor of NOX4, or a hydrogen peroxide scavenger to avoid insulin resistance is simply trying to block a perfectly adaptive response to a reasonable dose of fructose.
All that's needed to avoid a pathological response to fructose is to avoid ingesting a pathological dose of the stuff. There is actually quite a lot of evidence to suggest that physiological levels of uric acid production might be beneficial...
Peter
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Thursday, May 18, 2017
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Fructose and metabolic syndrome: Uric acid
Mulkidjanian: Na+ pump or Na+/H+ antiporter?
Mulkidjanian is a co-worker with Skulachev and extremely wedded to the primacy of Na+ bioenergetics, which is good. He has been looking at NuoH and NuoN subunits of complex I and their phylogenetics. In contrast to this, in the past I've discussed similarities between NuoH and NuoL. You just have to accept we're never going to be certain which component of complex I is most closely related to another... Anyway, I like this paper:
Phylogenomic Analysis of Type 1 NADH:Quinone Oxidoreductase
"Two recently published works independently noted the structural similarity between the NuoH and NuoN subunits and suggested their origin by some ancestral membrane protein duplication [13, 14]. Our analysis does not exclude the possibility that this duplication may have occurred even before the LUCA stage. In this case the initial NDH-1 form [proto-Ech in my terminology] had only one type of membrane subunit (the ancestor of NuoN and NuoH), which could function as a sodium transporter. The duplication of the gene would result in a different subunit, which improved the kinetic effectiveness of the redox-dependent sodium export pump (that participated in maintenance of [K+]/[Na+] greater than 1 in a primal cell) by facilitating proton translocation in the reverse direction".
Bear in mind that none of us can be certain exactly what a given protein might have been doing based on these family trees of genes.
I think there is general agreement that ancestor of NuoH and NuoN is a membrane pore and that it is primordial. In Mulkidjanian's scenario that pore is associated with a redox driven hydrogenase. His idea is that the hydrogenase is using preformed ferredoxin, or something similar, to extrude Na+ ions from the cell. This requires an external source of energy and his concept is for ZnS catalysed photosynthesis giving a localised organic "soup", ie heterotrophy. The refs are here and here. The source of K+ for the primordial cell cytoplasm is suggested here. I have to say, I'm not a convert to these aspects of his ideas, I'm staying more aligned with autotrophic thinking...
My own view is that the pore was a duct to localise oceanic acidic pH tightly to an NiFeS hydrogenase within alkaline vent "cytoplasm" to allow the hydrogenase to reduce ferredoxin, the primary energy currency of the proto-cell. The power source is the pH differential across an internal FeNiS moiety within the hydrogenase, combined with molecular hydrogen as the electron donor to reduce ferredoxin and so, eventually, CO2.
Given the almost certain ancestral gene duplication it is not difficult to make an antiporter out of NuoH/NuoN, whether you consider the ancestor to have been a proton pore or part of a Na+ pump. Even today, the membrane component of Complex I functions as an antiporter for Na+/H+ provided you separate it off from the hydrophilic matrix section:
The deactive form of respiratory complex I from mammalian mitochondria is a Na+/H+ antiporter
Given an antiporter sitting in a Na+ opaque membrane we can antiport a ton of Na+ out of the cell using a geological proton gradient to give us the result of a low intracellular Na+ concentration. Excess Na+ extrusion can be converted, by electrophoresis, to an elevated K+ inside giving the modern intracellular composition. In the early days the electrophoresis might not have been K+ specific, theoretically any positive ion other than Na+ would do. K+ is the long term preferred option.
As soon as we leave the vent there is no free antiporting so we need to have a system which provides energy to generate a Na+ potential (buffered by K+ electrophoresis). The power available to do this becomes very limited in the absence of a geothermal proton gradient, when all that is available is the reduction of CO2 using H2, the Wood #8211;Ljungdahl pathway. The Na+ chemiosmotic circuit then comes in to it's own as a system for combining small amounts of free energy in to units large enough to generate one ATP molecule. Recall how the modern pyrophosphatase Na+ pump requires the hydrolysis of four PPi to give one ATP via chemiosmotic addition. Until the advent of photosynthesis and the possibility of heterotrophy, all free living prokaryotes would have been autotrophic and living on a meagre energy budget.
The switch from luxurious hydrothermal vent conditions to lean autotrophic conditions goes a long way to explaining the universality of chemiosmosis. Alkaline hydrothermal vents may be stable on geological time scales but not for 4 billion years of un-interrupted flow and if the Wood #8211;Ljungdahl pathway is all there is to replace the vent power supply it's going to be chemiosmosis all the way...
Peter
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Thursday, May 18, 2017
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Life (16) Mulkidjanian: Na+ pump or Na+/H+ antiporter?
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About Me
Peter
I am Petro Dobromylskyj, always known as Peter. I'm a vet, trained at the RVC, London University. I was fortunate enough to intercalate a BSc degree in physiology in to my veterinary degree. I was even more fortunate to study under Patrick Wall at UCH, who set me on course to become a veterinary anaesthetist, mostly working on acute pain control. That led to the Certificate then Diploma in Veterinary Anaesthesia and enough publications to allow me to enter the European College of Veterinary Anaesthesia and Analgesia as a de facto founding member. Anaesthesia teaches you a lot. Basic science is combined with the occasional need to act rapidly. Wrong decisions can reward you with catastrophe in seconds. Thinking is mandatory.
I stumbled on to nutrition completely by accident. Once you have been taught to think, it's hard to stop. I think about lots of things. These are some of them.
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Organisation (or lack of it)!
The "labels" function on this #160;blog has been used to #160;function as an index and I've tended to group similar subjects together by using labels starting with identical text. If they're numbered within a similar label, start with (1). The archive is predominantly to show the posts I've put up in the last month, if people want to keep track of recent goings #160;on. #160;I might change it to the previous week if I ever get to time to put up enough posts in a week to justify it. #160;That seems to be the best I can do within the limits of this blogging software!
Blog Archive
#9660; #160;
2017
(32)
#9660; #160;
August
(1)
Metformin (02) The dose makes the poison
#9658; #160;
July
(2)
#9658; #160;
June
(2)
#9658; #160;
May
(4)
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April
(5)
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March
(11)
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February
(7)
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2016
(35)
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December
(2)
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November
(1)
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September
(2)
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August
(5)
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July
(2)
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May
(6)
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April
(7)
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March
(2)
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February
(5)
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January
(3)
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2015
(44)
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December
(3)
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November
(2)
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October
(4)
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September
(1)
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August
(7)
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July
(5)
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June
(7)
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May
(4)
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March
(5)
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February
(3)
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January
(3)
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2014
(27)
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December
(1)
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November
(2)
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October
(3)
#9658; #160;
September
(3)
#9658; #160;
July
(1)
#9658; #160;
June
(4)
#9658; #160;
May
(3)
#9658; #160;
April
(1)
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March
(1)
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February
(2)
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January
(6)
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2013
(38)
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December
(3)
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November
(4)
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October
(1)
#9658; #160;
September
(4)
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August
(4)
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July
(2)
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June
(2)
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May
(4)
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April
(2)
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March
(7)
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February
(3)
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January
(2)
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2012
(56)
#9658; #160;
December
(4)
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November
(7)
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October
(4)
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September
(3)
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August
(12)
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July
(6)
#9658; #160;
June
(9)
#9658; #160;
May
(1)
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April
(2)
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March
(2)
#9658; #160;
February
(3)
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January
(3)
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2011
(53)
#9658; #160;
December
(2)
#9658; #160;
November
(3)
#9658; #160;
October
(4)
#9658; #160;
September
(4)
#9658; #160;
August
(3)
#9658; #160;
July
(2)
#9658; #160;
June
(4)
#9658; #160;
May
(12)
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April
(7)
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March
(6)
#9658; #160;
February
(6)
#9658; #160;
2010
(75)
#9658; #160;
December
(2)
#9658; #160;
November
(1)
#9658; #160;
October
(2)
#9658; #160;
September
(5)
#9658; #160;
August
(5)
#9658; #160;
July
(13)
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June
(5)
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May
(2)
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April
(3)
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March
(11)
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February
(14)
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January
(12)
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2009
(95)
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December
(9)
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November
(12)
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October
(12)
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September
(14)
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August
(12)
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July
(2)
#9658; #160;
June
(6)
#9658; #160;
May
(1)
#9658; #160;
April
(1)
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March
(6)
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February
(12)
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January
(8)
#9658; #160;
2008
(142)
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December
(5)
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November
(5)
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October
(9)
#9658; #160;
September
(11)
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August
(17)
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July
(6)
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June
(12)
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May
(12)
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April
(11)
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March
(21)
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February
(15)
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January
(18)
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2007
(54)
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December
(18)
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November
(18)
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October
(6)
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September
(2)
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August
(1)
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July
(3)
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June
(4)
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January
(2)
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2006
(6)
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December
(1)
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November
(3)
#9658; #160;
October
(2)
Labels
A bit more on ketones and diabetic nephropathy
(1)
A brief discussion of ketosis
(1)
A defect of fat metabolism and a few thanks
(1)
A glimmer of light
(1)
A heads up
(1)
A little more on PCSK9 inhibitors
(1)
A load of crap in Gartnavel
(1)
A Peek at Paleo
(1)
A tale of two abstracts
(1)
ACCORD and musings on insulin
(1)
Acetoacetate and arterial oxygen tension
(1)
Acetone to oxaloacetate
(1)
Acipimox (2) and weight gain
(1)
Acipimox and insulin action
(1)
Adipotide and the Bad Fat
(1)
Adrian Ballinger on Everest
(1)
AGE RAGE and ALE (1): The AGE of LDL
(1)
AGE RAGE and ALE (2): The ALE of LDL
(1)
AGE RAGE and ALE (3): oxLDL
(1)
AGE RAGE and ALE (4): segregation
(1)
AGE RAGE and ALE (5): fasting
(1)
AGE RAGE and ALE (6): low fat
(1)
AGE RAGE and ALE (7): VLDL degradation
(1)
AGE RAGE and ALE (8): VLDL degradation and Krauss
(1)
AGE RAGE and ALE (9): VLDL degradation and Fish Oil
(1)
AGE RAGE and ALE posts (10): small dense Krauss
(1)
AGE RAGE and ALE posts (11): linoleic acid
(1)
Alcohol and fructose are the same to your liver
(1)
Alzheimer #39;s
(1)
Alzheimers and ketones
(1)
Alzheimers and omega 6s
(1)
Alzheimers and Tau proteins (1)
(1)
Alzheimers and Tau proteins (2)
(1)
Amgen share price and PCSK9 inhibition with Repatha
(1)
Amgen share price and PCSK9 inhibition with Repatha (2)
(1)
An aside on psychiatric links from Sid Dishes
(1)
An embarrassment of cress
(1)
An Error
(1)
Anacetrapib and phytotoxins
(1)
Anger vs diet in Japan
(1)
Animal fat and cholesterol
(1)
Are humans just multicellular yeasts?
(1)
Are ketone esters dangerous?
(1)
Arteriosclerosis (1) in 1957
(1)
Arteriosclerosis (2) and sulphation factor
(1)
Arteriosclerosis (3) and von Willebrand Disease
(1)
Arteriosclerosis (4) GAG and sudden death
(1)
Arteriosclerosis (5) GAG and sudden death part two; the pictures
(1)
Arteriosclerosis (6) and Subbotin
(1)
Arteriosclerosis and saturated fat
(1)
Arteriosclerosis and the breeder rat
(1)
Arteriosclerosis images (2): Models
(1)
Athletic acid reflux
(1)
Atrial tachycardia and fibrillation
(1)
Axen and Axen (1)
(1)
Axen and Axen (2)
(1)
Axen and Axen (3) Hawks
(1)
Axen and Axen (4) Ketogenic insulin resistance. It #39;s all over now...
(1)
Axen and Axen (5) The tradition continues
(1)
Back on line
(2)
Best ever statin study comment?
(1)
Best ever statin study?
(1)
Bob Michell on meta-analysis
(1)
Boiled mashed potatoes for miracle weight loss?
(1)
Boxes
(1)
Brain on a statin
(1)
Brain on chocolate
(1)
Breast cancer and starch
(1)
Breast cancer BRCA1 and metabolic syndrome
(1)
butter and leptin receptors: Speculation!
(1)
Butter insulin and Dr Davis
(1)
Can linoleic acid keep you slim?
(1)
Cancer and ketones
(1)
Cardiac ischaemia and low carbohydrate diets
(1)
Casein and gluten and gastric pH
(1)
Casein vs gluten
(1)
Cat rawfeeding; scroll down the comments
(1)
Cholesterol (the HDL sort) kills?
(1)
Cholesterol and Carruthers
(1)
Cholesterol and cholestyramine
(1)
Cholesterol and heart attack survival
(1)
Cholesterol and innate immunity
(1)
Cholesterol and memory
(1)
Cholesterol and Son of J-LIT
(1)
Cholesterol and the J-LIT study
(1)
Cholesterol and the J-LIT update
(1)
Cholesterol fed rabbit
(1)
Cholesterol heart attacks and JUPITER
(1)
Cholesterol hypothesis in 2010
(1)
Cholesterol hypothesis in 2010 part 2
(1)
Cholesterol JUPITER link
(1)
Cholesterol Milano style
(1)
Cholesterol pacitimbe and ACAT
(1)
Cholesterol presentation: Between countries
(1)
Cholesterol ratios through the looking glass
(1)
Cholesterol ratios: Torcetrapib again
(1)
Cholesterol reflectivity at 400nm
(1)
Cholesterol within nations studies
(1)
Cholesterol; it #39;s not a competition
(1)
Cholesterol; MESA and EBCT
(1)
Cholesterol; statins kill?
(1)
Cholesterol: ASTEROID destroys lipid hypothesis
(1)
Cholesterol: Do chylomicrons clog your arteries?
(1)
Cholesterol: Do chylomicrons clog your arteries? (2)
(1)
Cholesterol: LCAT and rabbits
(1)
Cholesterol: LDL in Oslo
(1)
Cholesterol: More epidemiology
(1)
Cholesterol: Near miss in Edinburgh
(1)
Cholesterol: Peto seeing some light?
(1)
Cholesterol: statins and oxLDL
(1)
Cirrhosis and corn oil
(1)
Cirrhosis and fish oil
(1)
Cirrhosis and fructose
(1)
Clofibrate and PUFA
(1)
Coconuts and Cornstarch in the Arctic?
(1)
Colorectal cancer and cholesterol
(1)
Colorectal cancer; fiber and the PPT
(1)
Complex I: Hoffer and B3
(1)
Conditioning Research on bad carbs
(1)
Confirmation Bias in my head
(1)
Confirmation bias is not just in my head
(1)
Costa del Glasgow
(1)
Crabtree and cardiovascular surgery
(1)
Cynthia Kenyon link
(1)
Dave Asprey and Dr Veech
(1)
David Blaine and refeeding syndrome
(1)
Dead people DO bleed...
(1)
Death by dogma
(1)
Denmark purchased using Flora profits?
(1)
DHA in rats
(1)
Diabetes and cardiac apotosis
(1)
Diabetes and hunger
(1)
Diabetes in Sweden
(1)
Diabetes in Sweden update
(1)
Diabetes; endothelial damage
(1)
Diabetic and hungry?
(1)
Diabetic nephropathy and the lost Swede
(1)
Diagnosing and Treating Vitamin B12 Deficiency Video
(1)
Do you believe in MRI scanners?
(1)
Dodgy D #39;Anci
(1)
Dr Davis links
(1)
Dr Doug Wallace on mitochondria
(1)
Dr Ravnskov on statins for primary prevention of CVD
(1)
Dr Uffe Ravnskov MD PhD interview
(1)
Dr Wolfgang Lutz Obituary
(1)
Dunnigan Familial Partial Lipodystrophy
(1)
Earning a crust
(1)
Easiyo
(1)
Eat as much starch as you wish
(1)
EBCT scan
(1)
EFA deficiencies?
(1)
Eggs are here
(1)
Eggs in Ontario
(1)
Electron Transport Chain image
(1)
Endotoxin Absorption on a High Fat Diet
(1)
Endurance and oxygen flux during fatty acid oxidation
(1)
Energy expenditure in obese vs slim non dieters
(1)
EPIC HbA1c and heart attacks
(1)
Essential fatty acids are essential
(1)
Excession
(1)
Familial Hypercholesterolaemia
(1)
Familial Hypercholesterolaemia and glucose
(1)
Familial Hypercholesterolaemia and porcelain
(1)
Familial Hypercholesterolaemia Brown and Goldstein
(1)
Familial Hypercholesterolaemia heterozygous survival
(1)
Fasting insulin and weight loss
(1)
Fasting insulin and weight loss and calories-in vs calories-out
(1)
Fasting insulin and weight loss on a water fast
(1)
Fat storage and retrieval
(1)
Fathead Supersize Me and Sweden
(1)
Fathead Supersize Me and Sweden (2)
(1)
Fats and absorbing endotoxin
(1)
Fiaf (1) Who #39;s fat is it anyway?
(1)
Fiaf (2) starving amidst plenty
(1)
Fiaf (3) where next?
(1)
Fiaf (4) memes and fat
(1)
Fiaf (5) Meme Watching
(1)
Fiber inulin and cancer
(1)
Fiber sucrose and ulcers
(1)
FIRKO mice
(1)
FIRKO-isation without all the hassle?
(1)
FIRKO-ise
(1)
First meat
(1)
Flow Mediated Dilation: What does it mean?
(1)
Folate and homocysteine
(1)
Food fermented cream
(1)
Food; carnitas
(1)
Food; chicken salsa
(1)
Food; Mutton followed by cheesecake
(1)
Food; sausages
(1)
Food; steak and kidney casserole
(1)
Food: African Beef Stew
(1)
Food: Burgers
(1)
Food: Lardo; the real thing
(1)
Food: Liver and bacon
(1)
Food: Liver; can you over do it?
(1)
Food: Mutton or lamb in orange sauce
(1)
Food: Offal
(1)
Food: Optimal ice cream
(1)
Food: Pork in green salsa and random dessert
(1)
Food: Recipe group
(1)
Food: steak and kidney casserole
(1)
French paradox in Sweden
(1)
Fructose and gout (1)
(1)
Fructose and gout (2)
(1)
Fructose and heart attacks
(1)
Fructose and lactic acid in Naked Mole Rats
(1)
Fructose and leptin
(1)
Fructose and metabolic syndrome: Uric acid
(1)
Fructose and triglycerides
(1)
Fructose Glucose and Cholesterol
(1)
Fruit and vegetables (1) cause DNA damage
(1)
Fruit and vegetables (1) re post
(1)
Fruit and vegetables (10) WHI and cancer
(1)
Fruit and vegetables (11) link
(1)
Fruit and vegetables (12) WHEL and CVD
(1)
Fruit and vegetables (13) become eggs
(1)
Fruit and vegetables (2) damage your DNA... latest study headline
(1)
Fruit and vegetables (3) last post (almost)
(1)
Fruit and vegetables (4) The asterisk
(1)
Fruit and vegetables (5) in Holland
(1)
Fruit and vegetables (6) WHEL study
(1)
Fruit and Vegetables (7) Mediterranean France
(1)
Fruit and vegetables (8) WHEL study and McDougall
(1)
Fruit and vegetables (9) potato fruits
(1)
Fruit Flies and NDI1
(1)
FSA apple
(1)
FSA in Glasgow
(1)
Getting fat (1) staying fat
(1)
Getting fat (2) staying fat; follow on
(1)
Getting fat (3) is good
(1)
Getting fat (4) is bad when you stop
(1)
Getting fat (5) Hunger
(1)
Getting fat is good (6) Official
(1)
Glucosamine and aged mice
(1)
Glucose as a cure for hypertriglyceridaemia?
(1)
Glucose from fatty acids: RQ of 0.454
(1)
Glucose lactate and cancer
(1)
Gluten and cardiomyopathy
(1)
Gluten and gall bladders
(1)
Gluten and NK cells (forget the antibodies)
(1)
Gluten and rheumatoid arthritis
(1)
Gluten and schizophrenia SPECT scan
(1)
Gluten ataxia
(1)
Gluten coeliac and multiple sclerosis
(1)
Gluten Dr Briffa link
(1)
Gluten links from Bloggeier
(1)
Gluten poppy pictures
(1)
Gluten-Congratulations: You have coeliac disease
(1)
Gluten; thyroid and auto immunity
(1)
Gluten: Does coeliac disease require an infection?
(1)
Gluten: Not your average plant toxin?
(1)
Gluten: The NICE guidelines for UK diagnosis
(1)
Glycaemic load and breast cancer
(1)
Gourmand Rats?
(1)
GSD IIIa ketones MAD and Veech again
(1)
GSD type I vs GSD type III: Cornstarch vs ketones
(1)
Guess the weight of the mouse competition
(1)
Gwyneth Paltrow has osteopaenia
(1)
Hazel eats butter
(1)
HbA1c and Familial Hypercholesterolaemia
(1)
HbA1c: Crack vs smack for a lower reading?
(1)
HbA1c: Low glucose and acid (palmitic)
(1)
Heart failure and insulin resistance
(1)
Helicobacter and glucose
(1)
Helicobacter and hydrogen
(1)
Hepatic extraction of fructose
(1)
Hepatic insulin resistance
(1)
Hepatic insulin resistance in KD fed mice
(1)
Hepatic insulin resistance through caloric overload
(1)
Heroin and IBS
(1)
High fat diet and fertility
(1)
High fat diets make you fat and stupid (1)
(1)
High fat diets make you fat and stupid (2)
(1)
High fat Dutch style
(1)
High fat fed mice on stearic acid
(1)
High fat meal is analgesic
(1)
HLA-B27 and Ebringer
(1)
HLA-B27 and Ebringer BSE text
(1)
HLA-B27 and Ebringer speech text
(1)
HLA-B27 some more
(1)
HOW MANY bananas a day?
(1)
How many eggs per day?
(1)
How toxic is wheat?
(1)
Hunting gathering and starving
(1)
Hyperglycaemia and free radicals
(1)
Hyperglycaemia is bad
(1)
If there were time...
(1)
IHD and ghee
(1)
IHD single vessel disease
(1)
IHD Tracking plaque 1950s style
(1)
Impaired glucose tolerance in low-carbohydrate diet: maybe only a physiological state
(1)
In the gym
(1)
Inhibiting lipolysis using acipimox
(1)
Insulin and confusion
(1)
Insulin and the Rewards of overfeeding
(1)
Insulin detemir (1)
(1)
Insulin detemir (2)
(1)
Insulin detemir (3)
(1)
Insulin glucagon and protein
(1)
Insulin in the brain: Hyperphagia?
(1)
Insulin in the brain: off topic giggle
(1)
Insulin; the Un-dead and coffin nails
(1)
Insulin: Are you hungry?
(1)
Insulin: Are you hungry? Part 2
(1)
Insulin: The Flatline Days
(1)
Intellectual honesty vs obfuscation
(1)
Interesting times on Mars
(1)
Intimal wall volume reductions with weight loss
(1)
It #39;s never too late to normalise your glucose (so long as you are still alive)
(1)
Jan Kwasniewski comment
(1)
Japan and a Seven Countries Study follow on
(1)
Jebb VS Nutt
(1)
Jimmy Moore on Dr Weil
(1)
John Hawks on Paleo in NY
(1)
Junk Food binge
(1)
Just a heads-up
(1)
Just a little on complex I and models
(1)
Kebabs
(1)
Ketoacidotic death in lactation!
(1)
Ketogenic Diet: Eat Food
(1)
Ketogenic vs moderate carbohydrate diets
(1)
Ketones for ALS?
(1)
Ketones without the side order of Danish Pastry please
(1)
Ketones: Should idiots be allowed to write the methods section of any quot;scientific quot; paper?
(1)
Ketosis and Protein
(1)
Ketosis links
(1)
Kitava: uric acid
(1)
Kwasniewski and cancer
(1)
Kwasniewski paper
(1)
Kwasniewski; praise the lard
(1)
Latest obesity paradox
(1)
Let them eat fat: Ron Rosenbaum
(1)
Life (01) Random musings on carbon monoxide
(1)
Life (02) Polyprenyl derivatives at the origin of life
(1)
Life (03) ATP synthase
(1)
Life (04) On the bench top
(1)
Life (05) Why sodium ions?
(1)
Life (06) What #39;s wrong with sodium ions?
(1)
Life (07) Two timelines
(1)
Life (08) Proto-Ech
(1)
Life (09) Ech
(1)
Life (10) Methyltransferase in methanogens
(1)
Life (11) Ferredoxin
(1)
Life (12) Loki and its membrane potential
(1)
Life (13) Skulachev in 1978
(1)
Life (14) From Skulachev to LUCA
(1)
Life (15) Skulachev addendum
(1)
Life (16) Mulkidjanian: Na+ pump or Na+/H+ antiporter?
(1)
Life (17) Nick Lane on Proto-Ech
(1)
Life (18) Why stop at formaldehyde?
(1)
Linoleic acid and Tuberous Sclerosis
(1)
Lipid blockage
(1)
Lipoprotein(a) a prickly subject
(1)
Lipoprotein(a) and ascorbate
(1)
Lipoprotein(a) and DELTA
(1)
Lipoprotein(a) and genetics
(1)
Lipoprotein(a) and oxidised cholesterol
(1)
Lipoprotein(a) and oxidised lipids: What #39;s your mimium requirement?
(1)
Lipoprotein(a) and the Fairies at the bottom of my garden
(1)
Lipoprotein(a) and tissue transglutaminase
(1)
Lipoprotein(a) Bantu recap
(1)
Lipoprotein(a) Bantu recap 2
(1)
Lipoprotein(a) genetics press release
(1)
Lipoprotein(a) is oxidised
(1)
Lipoprotein(a) Oxford abstract
(1)
Lipoprotein(a); Bantu Lp(a) and Swedish Lp(a)
(1)
Lipoprotein(a): 7-ketocholesterol and cancer
(1)
LIRKO mice (1)
(1)
LIRKO mice (2)
(1)
LIRKO mice (3) The MCQ
(1)
Liver and insulin (not a cooking recipe...)
(1)
Liver and onions at 100 after Keep Fit
(1)
Living on Kitava
(1)
Long time no post
(1)
Losing the plot
(1)
Low carbohydrate high protein and ApoE-/- mice
(1)
Low carbohydrate high protein and ApoE-/- mice (2)
(1)
Low fat and FMD
(1)
Low fat moods
(1)
Macrobiosis
(1)
Maria Thommessen
(1)
Maternal Diet Affects Offspring Preferences
(1)
Meet the researchers with the PKC味 deletion
(1)
Metabolism nuts and bolts
(1)
Metabolism nuts and bolts PUFA
(1)
Metabolism; mitochondria and uncoupling
(1)
MetFlex01 Did you over eat yourself in to obesity or T2DM?
(1)
MetFlex02 Insulin resistant and slim. How slim?
(1)
MetFlex03 Adipocyte insulin resistance
(1)
Metflex04 The Adipostat balloon
(1)
Metflex05 Metabolic flexibility and the identical twins
(1)
Metformin (01) Insulin
(1)
Metformin (02) The dose makes the poison
(1)
Methylglyoxal on Atkins... Uh oh
(1)
MGmin-LDL
(1)
Mice and breast cancer
(1)
Mid Winter break
(1)
Mitochondria in cancer cells
(1)
More fighting talk
(1)
More of the 17% solution
(1)
More yawns on insulin and knockout mice
(1)
Mortality and cholesterol
(1)
Multiple Sclerosis and Hydrogen
(1)
Multiple Sclerosis and Optic Neuritis
(1)
Musing about linoleic acid
(1)
NAFLD model based on fish oil
(1)
Naked mole-rats
(1)
NASH on a ketogenic diet
(1)
Neuron fuel and function
(1)
Niacin and adrenochrome
(1)
Niacin and beta hydroxybutyrate
(1)
Nicotine on the move
(1)
Nissen on Niaspan
(1)
Normoglycaemia independent of insulin?
(1)
Not really about swimming underwater
(1)
Not really much about swimming underwater (2)
(1)
Omega 3s and g-protein coupled receptors
(1)
On drinking varnish
(1)
On GLUT5
(1)
On Stephen Phinney and an RQ of 0.62
(1)
On the plus side for fish (oils?)
(1)
Overfeeding humans: Jebb
(1)
Paignton Zoo
(1)
Paleo and fructose
(1)
Palmitic acid and hyperglycaemia in diabetic heart failure (1)
(1)
Palmitic acid based food vs olive oil or corn oil supplements
(1)
Palmitic acid: the horror never ends
(1)
Palmitic acid: the horror never ends addendum
(1)
Palmitic acid: the horror never ends speculation
(1)
Paradox: Obesity and heart failure
(1)
Paradoxes
(1)
Parkinson #39;s disease
(1)
PCOS and LC; is pregnancy a side effect?
(1)
PCSK9 inhibitors and upper limb amputations
(1)
Pellagra and SMON
(1)
Personalised nutrition: Eat fat
(1)
Peter eats vegetables
(1)
PharmAmorin
(1)
Physiological insulin resistance (1)
(1)
Physiological insulin resistance (2); Dawn Phenomenon
(1)
Physiological insulin resistance (3); Clarification of FBG
(1)
Physiological insulin resistance (4); Alzheimers
(1)
Physiological insulin resistance (5) The wild type mice
(1)
Physiological insulin resistance (6) The Terminator
(1)
Physiological insulin resistance (7) and palmitic acid again
(1)
Physiological insulin resistance (8) Chewing the FAT
(1)
Physiological insulin resistance (9) Dolphins
(1)
Physiological insulin restisance (8) Guess what?
(1)
Playing with salt and water
(1)
Polycystic Kidney Disease and mTOR
(1)
Polyp Prevention Trial and homocysteine
(1)
Potatoes and weight loss (1)
(1)
PPT and unreported side effects
(1)
Prize for worst misuse of a statin
(1)
Prof Yudkin on ascorbate
(1)
Professor John Yudkin and Dr Ancel Keys
(1)
Prokaryotic Microbes with Eukaryote-like Genes Found
(1)
PROSPER and Q10
(1)
Prostate cancer and citrate and maybe omega 3s
(1)
Prostate cancer paradox
(1)
Protein catabolism should generate an RQ of around 0.8
(1)
Protons (01): Where #39;s the pump?
(1)
Protons (02): Where #39;s the bias?
(1)
Protons (03): Superoxide
(1)
Protons (04): 25mmol/l
(1)
Protons (05): Fasting
(1)
Protons (06): Metformin
(1)
Protons (07): Lactate
(1)
Protons (08): FADH2:NADH ratios and MUFA
(1)
Protons (09): Palmitoleate
(1)
Protons (10): SCD1 knockout mice
(1)
Protons (11): Linoleic acid in the hypothalamus
(1)
Protons (12): The pancreas
(1)
Protons (13): Zero fat
(1)
Protons (14): Love your superoxide
(1)
Protons (15): SCD1 and the bomb
(1)
Protons (16): Physiological insulin resistance
(1)
Protons (17): Physiological insulin resistance addendum
(1)
Protons (18): Physiological insulin resistance addendum 2
(1)
Protons (19): The linoleic acid fed mice
(1)
Protons (20): Where is FeS cluster N-1a?
(1)
Protons (21): TFAM and behenic acid
(1)
Protons (22): Back to N-1a and a nice quote
(1)
Protons (23): NAD plus to NADH some more
(1)
Protons (24): Meet the glycerol 3 phosphate shuttle
(1)
Protons (25): Aside to T cells
(1)
Protons (26) Chowdhury and Crabtree play with mitochondria
(1)
Protons (27) Physiological insulin resistance again
(1)
Protons (28) Protons so far
(1)
Protons (29) Uncoupling with fatty acids
(1)
Protons (30) Uncoupling and metabolic rate in insulin resistance
(1)
Protons (31) insulin induced theromgenesis in the Pima
(1)
Protons (32) Post obese insulin induced thermogenesis
(1)
Protons (33) The mtG3Pdh knockout mice
(1)
Protons (34) Rotenone
(1)
Protons (35) TFAM-KO revisited
(1)
Protons (36) Glycolysis to lactate
(1)
Protons (37) full glycerophosphate shuttle knockout mice
(1)
Protons (38) and ultra low fat once more
(1)
Protons (39) mtG3Pdh and lactate vs pyruvate
(1)
Protons (40) Living without the glycerophosphate shuttle
(1)
Protons (41) Metformin in the liver
(1)
Protons (42) Metformin as the next epilepsy drug?
(1)
Protons (43) Metformin in muscle
(1)
Protons (44) Does fatty acid oxidation drive reverse electron transport and superoxide generation at complex I?
(1)
Protons (45) Obesity and diabetes
(1)
Protons (46) The destruction of complex I
(1)
Protons (47) More from Dr Speijer
(1)
PUFA table
(1)
Pyramids and arthritis
(1)
Queen Hatshepsut
(1)
Ratty at a year
(1)
Renal stones and the OD
(1)
Rheumatoid arthritis and fasting
(1)
Rheumatoid arthritis and kidney stones
(1)
Rho zero cells
(1)
Rimonabant and hemopressin
(1)
Rosuvastatin and insulin sensitivity
(1)
Saatchi on the OD?
(1)
Sabbatical
(1)
SAD vs Traditional Japanese diet
(1)
SAD vs Traditional Japanese diet (2)
(1)
Saturated fat and sdLDL?
(1)
Saturated fat and the FSA
(1)
Saturated fat meta analysis: Krauss
(1)
Selling fiber and bacteria
(1)
Shazia and Dr Clifton
(1)
Shewanella and electrons
(1)
Should we abandon the carbohydrate hypothesis of obesity?
(1)
Skirting around leptin
(1)
Slim mice which don #39;t fart
(1)
Some of us eat a high fat diet
(1)
Spawn of Satan in the gym
(1)
Starchy stable isotopes? I don #39;t think so!
(1)
Starvation and cancer growth: Sauer vs Lisanti
(1)
Statin plus fibrate sucks
(1)
Statin stupidity again
(1)
Statins CoQ and diabetes
(1)
Stearate
(1)
Stearic acid; FADH2; complex I and cancer
(1)
Sucrose in pregnancy
(1)
Sugar is addictive
(1)
Sugar poisoning
(1)
Surwit and sucrose or when is a high sucrose diet a high fat diet?
(1)
Sweden and diabetes again: Salty beer in Kiwiland
(1)
Sweden #39;s dietitian advice? No thank you.
(1)
Swedish children; dietary sins
(1)
Swedish children; dietary sins (2)
(1)
TCA rap
(1)
That poor old C57Bl/6 mouse
(1)
The P479L gene for CPT-1a and fatty acid oxidation
(1)
The 14.4% solution
(1)
The anacetrapib giggle
(1)
The Crabtree Effect and superoxide in diabetes
(1)
The degradation of mitochondrial research
(1)
The lost 300
(1)
The pathology of evolution
(1)
The thumb tack hypothesis
(1)
The Wall is coming down
(1)
Thoughts on problems with high fat diets
(1)
Thyroid and LC
(1)
Tom Naughton #39;s FSA post
(1)
Total Perspective Vortex and vegicide
(1)
Trans fats vs linoleic acid
(1)
TV Pantomine or the Oxford study
(1)
Two rat experiment
(1)
Unclean
(1)
Uncoupling and weight loss
(1)
Uncoupling control in defence of FFAs
(1)
Uncoupling in a can?
(1)
Urate ascorbate resveratrol and land mines
(1)
Vitamin D
(1)
Vitamin D and UV fluctuations
(1)
Vitamin D and UV fluctuations (2)
(1)
Vitamin D supplementation: Bad?
(1)
Vitamin D3 again
(1)
Vitamin D3 supplements
(1)
VMH injuries
(1)
von Gierke #39;s disease
(1)
Want some acid? Bad trip on palmitic...
(1)
We are not alone
(1)
Weight loss when it #39;s hard 1.
(1)
Weight loss when it #39;s hard 2. Diazoxide
(1)
Weight loss when it #39;s hard 4. Coming soon; son of diazoxide
(1)
Weight loss when it #39;s hard 5. Son of diazoxide
(1)
Weight loss when it #39;s not hard 3. Oops
(1)
What do I eat 2013 update
(1)
What do I eat? (1)
(1)
What do I eat? (2) recipes
(1)
What is the secret of time travel doing on Fry #39;s ass?
(1)
Wheat and lactase (2)
(1)
Wheat and lactase and cordain
(1)
Wheat and lactose (1)
(1)
Wheat Germ Agglutinin; how little is enough?
(1)
When is a high carbohydrate diet not a high carbohydrate diet? Ask a vegan?
(1)
When is a high fat diet a high fat diet? When there is no sucrose.
(1)
When is a high fat diet not a high fat diet?
(1)
When is a high fat diet not a high fat diet? Masai
(1)
When is a high fat diet not a high fat diet? Masai part 2
(1)
When is a high fat diet not a high fat diet? Stuff via Fanatic Cook
(1)
When is a high fat diet not? Bang on time example
(1)
When is a high fat diet not? More of the usual
(1)
When is a high fat diet really a high fat diet?
(1)
When is a ketogenic diet not a ketogenic diet?
(1)
When low fat wins
(1)
Where has the superoxide gone?
(1)
Where is the brain of Rosemary Stanton?
(1)
Who pays the piper
(1)
Who pays the piper (3) for arterial stiffness?
(1)
Who pays the piper (4) for arterial stiffness?
(1)
Who pays the piper (5) Ignorant or bent?
(1)
Who pays the piper (6) High fat diet drops HDL
(1)
Who pays the piper (7) Other lipids
(1)
Who pays the piper (8) Disturbed earth
(1)
Who pays the piper part 2
(1)
Why low carbohydrate for diabetes
(1)
Will fasting destroy your mitochondria? (No).
(1)
Will palmitic acid give you cancer or fuel metastasis?
(1)
Women #39;s Health Initiative and heart attacks
(1)
Wooo and the snps
(1)
Worms and Stress: Live long and Prosper
(1)
Would Franklin have taken a statin if they had been available in the 1800s?
(1)
Would you like soya oil poured over your methionine spiked casein?
(1)
Zetia; are things getting better?
(1)
#160;

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