tag:blogger.com,1999:blog-36840063.post5251899444790363399..comments2024-03-27T22:57:00.742+00:00Comments on Hyperlipid: Prostate cancer and citrate and maybe omega 3sPeterhttp://www.blogger.com/profile/14527788116058656094noreply@blogger.comBlogger19125tag:blogger.com,1999:blog-36840063.post-52546873258686232822021-03-22T05:09:40.898+00:002021-03-22T05:09:40.898+00:00Thanks altavista, over the years the Protons conce...Thanks altavista, over the years the Protons concept has had a lot of explanatory power. I'd forgotten writing the post. You could nowadays throw in the role of peroxisomes in generating cytosolic acetyl-CoA and NADH and the targeting of DHA +/- EPA to this organelle as subsequent generators of citrate and anabolic fatty acid precursors...<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-65737124217875592442021-03-21T18:22:24.823+00:002021-03-21T18:22:24.823+00:00This was a good post. I wished you followed up on ...This was a good post. I wished you followed up on italtavistahttps://www.blogger.com/profile/10443439015369042857noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-49700282179338018522014-06-22T05:49:55.976+00:002014-06-22T05:49:55.976+00:00What I was driving at is that prostate cells would...What I was driving at is that prostate cells would normally generate far more citrate than they need because it is usually exported in to the prostatic fluid. This appears to come from the first step of the TCA, using Zn to inhibit aconite. So if the cell is set up to meet it’s energy needs largely through glycolysis, without using it’s Zn-inhibited TCA, suddenly turning the TCA by loss of Zn inhibition will generate large amounts of NADH, for which the cell has no use. The ratio of NADH to NAD ratio appears to determine the malignancy, i.e. the cell has far more energy to grow with than it needs. Converting the NADH to NAD+ needs ox phos and will generate enlarge amounts of ATP in the process. The phenotype is a glycolysis dependent cell which cannot stop the glycolysis when presented with mitochondrial biogenesis.<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-44263692463196478842014-06-21T17:19:05.552+00:002014-06-21T17:19:05.552+00:00Hey Peter
Can you explain a little what you mean ...Hey Peter<br /><br />Can you explain a little what you mean by "take off with a large supply of NADH from the TCA" ? I dont have access to the fulltext of the paper. Do you mean the NADH (and NAD) ends up lost in semen or is metabolised to niacinamide and not recycled fast enough in the salvage pathway or ?<br /><br />ThxSamhttps://www.blogger.com/profile/04768653538599898702noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-24127901046361229132013-09-03T19:17:28.138+00:002013-09-03T19:17:28.138+00:00http://www.pnas.org/content/106/21/8665.full
1000...http://www.pnas.org/content/106/21/8665.full<br /><br />1000mg C 400iu E, as supplements. I can live with food content of these antioxidants but not as supplements...<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-38190015034944752502013-09-02T14:23:46.177+00:002013-09-02T14:23:46.177+00:00"C and E certainly blunt the beneficial effec..."C and E certainly blunt the beneficial effects of exercise..."<br /><br /><br />Is this only in high doses and not coming from diet? Zorica Vuletichttps://www.blogger.com/profile/05793548904884383364noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-52434527154392456182013-09-02T13:36:04.683+00:002013-09-02T13:36:04.683+00:00C and E certainly blunt the beneficial effects of ...C and E certainly blunt the beneficial effects of exercise. Why not those of metformin?<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-22590061847119661332013-09-02T03:11:21.744+00:002013-09-02T03:11:21.744+00:00Is free radical production part of the mechanism o...Is free radical production part of the mechanism of action of metformin? Does that mean that taking, say, large doses of vitamins C or E (both potent antioxidants) interferes with the action of metformin?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36840063.post-45587225334015645292013-09-01T19:43:38.923+00:002013-09-01T19:43:38.923+00:00Hi Zorica,
Metformin, however it pans out long te...Hi Zorica,<br /><br />Metformin, however it pans out long term, produces enough free radicals/depletes enough ATP to improve the health of diabetics. It is one of the few drugs ever to have profound anticancer effects long term. The correct amount of free radical production maximises mitochondrial biogenesis. Long term studies don't seem to be available in similar vein to the short term ones for metformin. Benefits of metformin seem to kick in after a few weeks, in people...<br /><br />Respiration, and by this I think we mean oxygen consumption, is key to life extension in many models. Fat requires more oxygen per unit ATP generation than carbohydrate. That looks like a Good Thing to me. I have an interesting paper by Cynthia Kenyon to discuss. Other models of life extension have genetically DAMAGED respiratory chains which respire very poorly. Life is complex.<br /><br />PetePeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-69091788542385981622013-09-01T00:43:02.390+00:002013-09-01T00:43:02.390+00:00"Metfomin certainly generated free radicals i..."Metfomin certainly generated free radicals in the short term, what happens after a week or two when intracellular lipids are depleted and insulin sensitivity improves is an interesting set of questions which may not be direct follow ons from the acute effects. AMP kinase does, without a doubt, upregulate and this will have all sorts of non-acute follow ons. There are a whole lot of similar questions as regards degree about hyperglycaemia per se which activates a whole stack of antioxidant processes in the cytoplasm which effectively wipe out the insulin activation signal. You have a ton of H2O2 in the cytoplasm which both causes insulin resistance at high doses combined with the response of antioxidant systems which, while stabilising the redox state under hyeprglycaemia, concurrently obliterate insulin activation once we really want it to work.<br /><br />Long term it seems to be the overactivity of the antioxidant systems and associated failure of insulin activation which are the bug bear in neurodegeneration."<br /><br />My understanding is that this is saying that long term metformin use obliterates insulin production (or is it insulin sensitivity)? How long term is long term? Is it only at excessive doses?<br /><br />I ask b/c my mom uses metformin for the past ~8 years now. Thanks.<br /><br /><br />". Measurement of the maximum activities of key enzymes of carbohydrate, fat, and amino acid catabolism in flight muscle and heart of rufous hummingbirds (Selasphorus rufus) reveals that the high ATP requirements of short-term hovering flight can only be supported by the oxidation of carbohydrate. Fat oxidation can support a substantially lower maximum rate of ATP turnover, indicating that this process can power only the lower +.++energetic requirements of long-term forward or migratory flight. Mitochondria isolated from flight muscle oxidize pyruvate and palmitoyl-CoA equally well. The inhibition of pyruvate oxidation by palmitoyl-CoA oxidation provides a mechanism by which fat oxidation inhibits carbohydrate oxidation in the transition from short- to long-term flight."<br /><br />I know we are not humming birds, but the idea of being in ketosis during long distance (ultra-marathon as opposed to regular marathons) is quite beneficial and for HIT type activities, more glucose is required. Fascinating. <br /><br />I also believe that for cows, although they eat grass/vegetation, and this is carbohydrate, that it is converted to fatty acid (ends up being processed in a fat fuel) is also quite interesting. <br /><br />I don't believe it's wise to copy the diets of other species, but the mechanisms under which work in other species seems quite appropriate in human contexts.Zorica Vuletichttps://www.blogger.com/profile/05793548904884383364noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-62307664322897882312013-08-14T20:46:49.227+00:002013-08-14T20:46:49.227+00:00Re: the hummingbird's metabolism:
Metabolic s...Re: the hummingbird's metabolism:<br /><br />Metabolic sources of energy for hummingbird flight 1986<br /><br />It has been known for some two decades that hovering flight in hummingbirds is the most energetically expensive muscle work known among vertebrates, but the metabolic support for such work has never been clarified. Measurement of the maximum activities of key enzymes of carbohydrate, fat, and amino acid catabolism in flight muscle and heart of rufous hummingbirds (Selasphorus rufus) reveals that the high ATP requirements of short-term hovering flight can only be supported by the oxidation of carbohydrate. Fat oxidation can support a substantially lower maximum rate of ATP turnover, indicating that this process can power only the lower +.++energetic requirements of long-term forward or migratory flight. Mitochondria isolated from flight muscle oxidize pyruvate and palmitoyl-CoA equally well. The inhibition of pyruvate oxidation by palmitoyl-CoA oxidation provides a mechanism by which fat oxidation inhibits carbohydrate oxidation in the transition from short- to long-term flight.<br /><br />http://ajpregu.physiology.org/content/251/3/R537<br /><br />Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-102482939700102512013-08-14T01:03:30.507+00:002013-08-14T01:03:30.507+00:00Thanks, Peter.
I am into health and endurance spo...Thanks, Peter.<br /><br />I am into health and endurance sports. I greatly appreciate articles and enjoy your writing style. I find your posts adds to my understanding of metabolism.<br /><br />-Robert Martin.Rockethttps://www.blogger.com/profile/09681365283925560039noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-7568263765311531302013-08-07T11:02:43.588+00:002013-08-07T11:02:43.588+00:00Thanks M, have downloaded. I did start scanning my...Thanks M, have downloaded. I did start scanning my copy but it was going to take waaaay more time than I had available.<br /><br />George, about a year ago I wanted to get on to PUFA, iron overload, copper overload and what a poor hepatocyte can do with more calories than it wants yet it fails to generate insulin resistance. Might try and link the two ideas together... <br /><br />I can see NAD+ precursors being helpful. I wonder how much good NADH per se would be without being pre-reduced to NAD+. Possible, but I'd like to see some sort of esoteric model of the sort I love!<br /><br />radian, I think it may be a matter of degree and duration. I'd have to go back to the original protons threads and check out succinate generated superoxide, palmiate superoxide and metformin superoxide. The trouble is you end up looking at different numbers from different papers, different experimental set ups and different methods of measurement of ROS. Metfomin certainly generated free radicals in the short term, what happens after a week or two when intracellular lipids are depleted and insulin sensitivity improves is an interesting set of questions which may not be direct follow ons from the acute effects. AMP kinase does, without a doubt, upregulate and this will have all sorts of non-acute follow ons. There are a whole lot of similar questions as regards degree about hyperglycaemia per se which activates a whole stack of antioxidant processes in the cytoplasm which effectively wipe out the insulin activation signal. You have a ton of H2O2 in the cytoplasm which both causes insulin resistance at high doses combined with the response of antioxidant systems which, while stabilising the redox state under hyeprglycaemia, concurrently obliterate insulin activation once we really want it to work.<br /><br />Long term it seems to be the overactivity of the antioxidant systems and associated failure of insulin activation which are the bug bear in neurodegeneration.<br /><br />Probably elsewhere too.<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-70908050868237829582013-08-07T05:49:08.492+00:002013-08-07T05:49:08.492+00:00"Aconitase is deliberately inhibited by Zn re..."Aconitase is deliberately inhibited by Zn retention and the citric acid of the citric acid cycle, which cannot be further metabolised in the said cycle, is then exported in to the prostatic fluid. In large amounts."<br /><br />I always wondered how and why fruit becomes full of citric acid and other TCA intermediates. It doesn't seem like the sort of thing that should be full of mitochondria. This kind of thing helps to resolve that old mystery.<br />oh, and fruit > seed > sperm - there's even a theme of sorts there.Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-51271896280438359122013-08-07T04:58:55.070+00:002013-08-07T04:58:55.070+00:00Completely unreasonable superoxide generation appe...<i> Completely unreasonable superoxide generation appears to trash the mtDNA</i><br /><br /> I probably misunderstand this, so here goes: does this imply that metformin, which generates high superoxide levels (as I understand another article here to mean), causes DNA damage?Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-36840063.post-13276700423288491252013-08-06T22:00:55.136+00:002013-08-06T22:00:55.136+00:00NADH as a medicine:
http://www.nadh-apotheke.eu/NA...NADH as a medicine:<br />http://www.nadh-apotheke.eu/NADH-Studien/THE%20ENERGIZING%20EFFECT%20OF%20NADH-COENZYME.pdfPuddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-81878466213115285032013-08-06T21:58:26.332+00:002013-08-06T21:58:26.332+00:00M, that's a great book. I also have The Pengui...M, that's a great book. I also have The Penguin Encyclopedia of Nutrition, 1985, which is witty and wise and where Yudkin nods to Paleo with sections on Neolithic Revolution and Dietary Instinct.<br />I'd like to see everything Yudkin wrote republished with introductions by various modern experts.<br />Especially This Slimming Business, if anyone knows where that is online.<br />I can only find this:<br />http://www.ncbi.nlm.nih.gov/pubmed/13787548<br />:(<br /><br />@ Peter - humming birds drink nectar of course, not pollen.<br /><br />With regard to citrate as fuel, remember that malate is touted as helpful in fibromyalgia because NADH is immediate TCA product.<br />And NADH supplements are useful in some brain disorders - is it MS? And would NAD+ be as useful, or more so?Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-91065096756698842062013-08-06T11:20:02.223+00:002013-08-06T11:20:02.223+00:00Peter, in case you don't have a PDF of the boo...Peter, in case you don't have a PDF of the book "Pure, White & Deadly", and would like one, here is a download. I've downloaded it and ran it through the scan and it contains no virus.<br /><br />https://docs.google.com/open?id=0B2FsXfJXQyd2QnNWYWpHQVJfLXMMhttps://www.blogger.com/profile/14679839426291667211noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-36236522302122972742013-08-06T08:08:39.123+00:002013-08-06T08:08:39.123+00:00This is great Peter.
you might even be able to mak...This is great Peter.<br />you might even be able to make sense of this:<br />http://www.ncbi.nlm.nih.gov/pubmed/18093684<br />Why does replacing some corn oil with MCTs make NASH worse (but replacing them all makes it much better)?<br /><br />Does the unusual energy arrangement in prostate cells have anything to do with the fructose requirement of sperm?<br />I think of certain high-CICO bee workers using honey for hive-warming purposes, or hummingbirds buzzing on pollen.Puddleghttps://www.blogger.com/profile/00953398103675945541noreply@blogger.com