tag:blogger.com,1999:blog-36840063.post2096722808800126657..comments2024-03-27T22:57:00.742+00:00Comments on Hyperlipid: EchPeterhttp://www.blogger.com/profile/14527788116058656094noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-36840063.post-74304385663855399072015-08-03T07:34:13.800+00:002015-08-03T07:34:13.800+00:00Ok, I think I've at least found North now with...Ok, I think I've at least found North now with your question "...are we talking about a later change of ion rather than a later reversal of which channel is used for pumping when pumping is needed?"<br /><br />This is the BioServ F3666 Ketogenic diet (http://www.bio-serv.com/pdf/F3666.pdf) Lard, Butter, Corn Oil, Casein, Cellulose, Mineral Mix, Vitamin Mix, Dextrose. 42.5% SFAs, 40.4% MONOs, 17.1% PUFAs.<br /><br />Yes I was wondering about the lack of physiological IR - in humans we see it peripherally, but not in the brain if I recall correctly.<br /><br />ALT was high in both the long-term KD rats & the long-term normal Chow rats (even a bit higher in the normal chow ones actually). Really makes you think about how "good" normal rat chow is. Not a very high bar of health I fear.<br /><br />The abhorred Séralini (in the US that is, not in FR) published "Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests" in PLOS ONE on July 2 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128429 I haven't yet got round to reading it.<br /><br />"We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents" If the conclusions stand up, the implication for murine studies are disastrous...raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-63294134874855835932015-08-02T20:41:19.790+00:002015-08-02T20:41:19.790+00:00Raphi, it's not simple to see exactly how the ...Raphi, it's not simple to see exactly how the anti porter works. The generic amino acid essential to Na+ translocation appears to be the aspartic acid marked in red in the ribbon diagrams, which means that NuoH may be the Na+ pumping channel. Apparently you need at least two ion channels to anti port, it's never just one protein working like a seesaw... So which channel is the proton translocator and which is the Na+ translocator is not completely clear. The methanogen methyltransferase has three channels and the one thought to translocate Na+ has an aspartic acid in exactly the correct place to suggest it might be some sort of homologue of NuoH. Of course NuoH is the core of complex I and currently runs on H+ so are we talking about a later change of ion rather than a later reversal of which channel is used for pumping when pumping is needed? It's looking like NuoH was the one initially used for pumping Na+, which suggest that NuoL was the proton channel. Which is hard to make sense of! Unless NuoL could be shifted away from the NiFe hydrogenase as the vent gradient was lost.....<br /><br />It's interesting that people are finally looking at longevity in mice on ketogenic diets. The gain was small and ns, but any gain when you are eating enough omega 6 PUFA to cause NASH is quite impressive! There are an awful lot of questions raised by the study. Such as why no physiological insulin resistance????<br /><br />PeterPeterhttps://www.blogger.com/profile/14527788116058656094noreply@blogger.comtag:blogger.com,1999:blog-36840063.post-78710120053414636892015-08-02T08:46:28.368+00:002015-08-02T08:46:28.368+00:00Hi Peter,
So NuoH pushes NuoL to stop antiporting...Hi Peter,<br /><br />So NuoH pushes NuoL to stop antiporting and start Na+ pumping...interesting inhibition of one action leading the appearance of a new one. <br /><br />Somewhat off topic; your comment "I think that the initial gene duplication/modification would probably have produced an uncontrolled antiporter" reminds me of the competing hypotheses in genetics about subfunctionalization and neofunctionalization. Seems like subfunctionalization is the new kid on the block https://liorpachter.wordpress.com/2015/05/26/pachters-p-value-prize/<br /><br />Completely off topic but totally in your wheel house is "Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet". Here's the full-paper https://www.dropbox.com/s/cz4f91zjds3aqdu/Adaptive%20changes%20in%20amino%20acid%20metabolism%20permit%20normal%20longevity%20in%20mice%20consuming%20a%20low-carbohydrate%20ketogenic%20diet.pdf?dl=0 A lot of it isn't new to you but it's quite an interesting paper nonetheless.<br />- some interesting mouse model-dependent effects on total weight & lean/fat mass % ...here, mice weighed less than chow-fed counterparts but had better greater lean mass as a % of body weight<br />- 'paradox' in KD-fed mice between increased their hepatic beta-oxidation intermediates (acylcarnitine, carnitine) gene profiles & reduced serum acylcarnitine, carnitine<br />- in KD-fed mice "this down-regulation of AA catabolic genes likely offsets the low concentration of protein substrate in the diet"<br />- "KD consumption caused increases in the expression of chemokines/cytokines or genes related to pro-inflammatory pathways" with no effect on longevity<br /><br />Maybe you'll find an interesting take on it no one had the decency to think of...Wouldn't be the first time!raphihttps://www.blogger.com/profile/08992252569979714724noreply@blogger.com