User talk:Pippin2k
CHEMENG283 Wiki Project: Biochemical mechanisms of fructose toxicity
Evolutionary background
Excessive consumption of fructose-rich foods has been suggested to contribute to negative health outcomes.[1][2][3] Unlike glucose, whose metabolism is more rigorously controlled by the PFK1 enzyme, fructose is regulated and processed through metabolic pathways in a less complex manner. Fructokinase, the enzyme that activates fructose intracellularly via phosphorylation to commence its utilization, is not subject to negative feedback control from the downstream intermediates of glycolysis, the TCA cycle, or energy carriers.[4][5][6] This can result in large amounts of acetyl-CoA originating from the metabolism of fructose being fed into fatty acid biosynthesis pathways.[7][8] This increased flux through the fatty acid pathways results in highly elevated generation and accumulation rates for various fats. In some hibernating mammals, it is suggested that this deregulated utilization of fructose might have an advantageous adaptive role.[9] Rapid generation of fat storage when animals feed before the winter on seasonal ripe fruits, which are high in fructose, allows them to build a significant energy storage in a short time period. In some animals that are native to locations with pronounced seasonality, this mechanism also can contribute to fat accumulation to increase robustness and survive resource-scarce winters.[10] It is argued that this mechanism is also present in primates, including humans. Furthermore, its residual effects may cause more harm than benefit as hibernation is not a selective pressure in modern society and human metabolism has not evolved to handle excessive caloric/carbohydrate intake.[5][10]
Biochemical mechanisms
![](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b5/Fructose_Metabolism_Global.png/220px-Fructose_Metabolism_Global.png)
Moderate fruit consumption does not usually increase the blood levels of fructose since the small intestine uses it to generate glucose. [11] However, when fructose is artificially added in foods or when excessive amounts of fructose or sucrose-rich fruit is consumed, it can noticeably reach the systemic circulation.[12] The systemic bioavailability of fructose is positively correlated with increased de novo lipogenesis, decreased fatty acid oxidation, increased liver fat, postprandial triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL)-C, and C-reactive protein. These effects are substantially more pronounced in regards to fructose consumption when compared to excessive glucose intake.[13] Moreover, the lipogenic effects of fructose are exacerbated with the associated uptake of saturated fatty acids.[14] This compounding effect is quite likely fueled by diets containing fast foods that are both highly sweetened and processed in oils or high in fat.[15]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/8/87/Fructose_Metabolism.jpg/220px-Fructose_Metabolism.jpg)
Fructose metabolism intermediates can also activate the glycolytic pathway by entering through glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, which could be especially detrimental in cancer due to the Warburg effect.[16] Transient intracellular phosphate depletion due to the excessive phosphorylation of fructose by fructokinase may also affect purine metabolism resulting in increased production of uric acid. Uric acid, in turn, may further promote lipogenesis, as well as mediate other pathological processes that play an important role in the development of metabolic syndrome, high blood pressure, and gout.[17] Negative metabolic effects of fructose are compounded by its inability, unlike glucose, to induce satiety. This may be the reason for less controlled or excessive consumption of fructose-rich foods.[18]
Inhibition of fructose metabolism
Hereditary fructokinase deficiency does not appear to have any apparent negative health effects in humans[19] and may actually be associated with a better prognosis in populations where diets include large amounts of fructose.[20] It is possible that without normal fructokinase activity, metabolism of exogenous fructose would be decreased since fructose metabolites would be able to neither feed in acetyl-CoA generation nor upregulate lipid synthesis and accumulation. The excessive amount of fructose will simply be excreted with urine resulting in fructosuria, which is virtually a harmless health condition that could be incidentally found during a medical check-up for unrelated reasons.[21] It is shown that fructokinase inhibition might also be beneficial in ischemic acute kidney injury since, under this condition, fructose mediates oxidative stress and cell injury.[22][23] It is suggested that preventing or decreasing the metabolism of exogenous fructose will be beneficial in terms of carbohydrate and lipid metabolism as well as will decrease uric acid production which is beneficial as increased uric acid buildup triggers oxidative stress and inflammation.[24] Luteolin, an ingredient in some dietary supplements, was used in animal studies to inhibit fructose metabolism and showed beneficial effects in disrupting pathological processes mediated by fructose. However, the clinical relevance of these findings for humans is not known.[25]
March 2021
Hello, I'm Zefr. I noticed that you added or changed content in an article, Fructose, but you didn't provide a reliable source. It's been removed and archived in the page history for now, but if you'd like to include a citation and re-add it, please do so. You can have a look at the tutorial on citing sources. If you think I made a mistake, you can leave me a message on my talk page. Introduce major changes and controversial topics first on the talk page, then engage in discussion to obtain WP:CON. Zefr (talk) 15:13, 2 March 2021 (UTC)
- On my talk page, you said: As part of the biochemistry course that I take, I'm asked to contribute to a biochemistry-related topic on Wikipedia. This is done by others as well. Together with another person, I've chosen fructose. What exactly can I do to support the information I've posted? Is it possible that I add sources referencing scientific books and meta-analyses related to this topic? Or are direct citations expected? Also, I have a large text (almost 700 words). Should I post it all together at once? I'll appreciate any guidance.
- Reversion of this edit was justified because it contains speculation from primary lab research. When addressing health on Wikipedia, we use WP:MEDRS reviews, which mainly are in medical journals publishing results from large-scale clinical trials which are mainly absent from the fructose literature. The chemical section of the fructose article seems reasonably well-covered, with little reason to add to it, as this is an established science. See the left pyramid of WP:MEDASSESS where systematic reviews and meta-analyses of large-scale human research would be suitable, if from reputable sources. I understand that your biochemistry course may motivate you to use lab research as evidence, but such content is not encyclopedic, as it is not derived from the review literature; see WP:NOTJOURNAL #6-8. Also, it seems WP:OFFTOPIC to me to address highly speculative "evolutionary" concepts when there's such weak evidence for such an effect. No reputable review articles, medical associations, or regulatory agencies support such a concept; see WP:MEDREV. You can respond here on your page. Good luck. Zefr (talk) 16:11, 2 March 2021 (UTC)
- Can you please have a look at this then, Zefr? Below I provide the rest of the text (which is more connected to biochemistry). Also, we were planning to include two graphical schemes showing the connection between fructose and uric acid metabolism and a general overview of how fructose is included in the metabolism.
References
- ^ Bray GA, Nielsen SJ, Popkin BM (Apr 2004). "Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity". Cell. 79 (4): 537–43. doi:10.1093/ajcn/79.4.537. PMID 15051594.
- ^ Dornas WC, de Lima WG, Pedrosa ML, Silva ME (Nov 13, 2015). "Health implications of high-fructose intake and current research". Adv Nutr. 6 (6): 729–37. doi:10.3945/an.114.008144. PMID 26567197.
- ^ Kroemer G, López-Otín C, Madeo F, de Cabo R (Oct 18, 2018). "Carbotoxicity-Noxious Effects of Carbohydrates". Cell. 175 (3): 601–614. doi:10.1016/j.cell.2018.07.044. PMID 30340032.
- ^ Kratzer JT, Lanaspa MA, Murphy MN, Cicerchi C, Graves CL, Tipton PA, Ortlund EA, Johnson RJ, Gaucher EA (Mar 11, 2014). "Evolutionary history and metabolic insights of ancient mammalian uricases". Proc Natl Acad Sci U S A. 111 (10): 3763–8. doi:10.1073/pnas.1320393111. PMID 24550457.
- ^ a b Tesz GJ, Bence KK (Jul 7, 2020). "Finding the Sweet Spot: Parsing Tissue-Specific Contributions of Fructose Metabolism". Cell Metab. 32 (1): 6–8. doi:10.1016/j.cmet.2020.06.009. PMID 32640246.
- ^ Lim JS, Mietus-Snyder M, Valente A, Schwarz JM, Lustig RH (May 2010). "The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome". Nat Rev Gastroenterol Hepatol. 7 (5): 251–64. doi:10.1038/nrgastro.2010.41. PMID 20368739.
- ^ Douard V, Ferraris RP (Jan 15, 2013). "The role of fructose transporters in diseases linked to excessive fructose intake". J Physiol. 591 (2): 401–14. doi:10.1113/jphysiol.2011.215731. PMID 23129794.
- ^ Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ (Nov 2008). "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding". Am J Physiol Regul Integr Comp Physiol. 295 (5): R1370-5. doi:10.1152/ajpregu.00195.2008. PMID 18703413.
- ^ Stenvinkel P, Fröbert O, Anderstam B, Palm F, Eriksson M, Bragfors-Helin AC, Qureshi AR, Larsson T, Friebe A, Zedrosser A, Josefsson J, Svensson M, Sahdo B, Bankir L, Johnson RJ (Sep 9, 2013). "Metabolic changes in summer active and anuric hibernating free-ranging brown bears (Ursus arctos)". PLoS One. 8 (9): e72934. doi:10.1371/journal.pone.0072934. PMID 24039826.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ a b Johnson RJ, Stenvinkel P, Andrews P, Sánchez-Lozada LG, Nakagawa T, Gaucher E, Andres-Hernando A, Rodriguez-Iturbe B, Jimenez CR, Garcia G, Kang DH, Tolan DR, Lanaspa MA (Mar 2020). "Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts". J Intern Med. 287 (3): 252–262. doi:10.1111/joim.12993. PMID 31621967.
- ^ Jang S, Dilger RN, Johnson RW (Oct 2010). "Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice". J Nutr. 140 (10): 1892–8. doi:10.3945/jn.110.123273. PMID 20685893.
- ^ Rendeiro, C; Masnik, AM; Mun, JG; Du, K; Clark, D; Dilger, RN; Dilger, AC; Rhodes, JS (20 April 2015). "Fructose decreases physical activity and increases body fat without affecting hippocampal neurogenesis and learning relative to an isocaloric glucose diet". Scientific reports. 5: 9589. doi:10.1038/srep09589. PMID 25892667.
- ^ Jameel, F; Phang, M; Wood, LG; Garg, ML (16 December 2014). "Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation". Lipids in health and disease. 13: 195. doi:10.1186/1476-511X-13-195. PMID 25515398.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Chiu, S; Mulligan, K; Schwarz, JM (July 2018). "Dietary carbohydrates and fatty liver disease: de novo lipogenesis". Current opinion in clinical nutrition and metabolic care. 21 (4): 277–282. doi:10.1097/MCO.0000000000000469. PMID 29697539.
- ^ DiNicolantonio, JJ; Lucan, SC; O'Keefe, JH (March 2016). "The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease". Progress in cardiovascular diseases. 58 (5): 464–72. doi:10.1016/j.pcad.2015.11.006. PMID 26586275.
- ^ Nakagawa, T; Lanaspa, MA; Millan, IS; Fini, M; Rivard, CJ; Sanchez-Lozada, LG; Andres-Hernando, A; Tolan, DR; Johnson, RJ (2020). "Fructose contributes to the Warburg effect for cancer growth". Cancer & metabolism. 8: 16. doi:10.1186/s40170-020-00222-9. PMID 32670573.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Kroemer, G; López-Otín, C; Madeo, F; de Cabo, R (18 October 2018). "Carbotoxicity-Noxious Effects of Carbohydrates". Cell. 175 (3): 605–614. doi:10.1016/j.cell.2018.07.044. PMID 30340032.
- ^ Page, KA; Chan, O; Arora, J; Belfort-Deaguiar, R; Dzuira, J; Roehmholdt, B; Cline, GW; Naik, S; Sinha, R; Constable, RT; Sherwin, RS (2 January 2013). "Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways". JAMA. 309 (1): 63–70. doi:10.1001/jama.2012.116975. PMID 23280226.
- ^ Tran, C (3 April 2017). "Inborn Errors of Fructose Metabolism. What Can We Learn from Them?". Nutrients. 9 (4). doi:10.3390/nu9040356. PMID 28368361.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Andres-Hernando, A; Orlicky, DJ; Kuwabara, M; Ishimoto, T; Nakagawa, T; Johnson, RJ; Lanaspa, MA (7 July 2020). "Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction". Cell metabolism. 32 (1): 117-127.e3. doi:10.1016/j.cmet.2020.05.012. PMID 32502381.
- ^ Froesch, ER (November 1976). "Disorders of fructose metabolism". Clinics in endocrinology and metabolism. 5 (3): 599–611. doi:10.1016/s0300-595x(76)80042-4. PMID 189957.
- ^ Andres-Hernando, A; Li, N; Cicerchi, C; Inaba, S; Chen, W; Roncal-Jimenez, C; Le, MT; Wempe, MF; Milagres, T; Ishimoto, T; Fini, M; Nakagawa, T; Johnson, RJ; Lanaspa, MA (13 February 2017). "Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice". Nature communications. 8: 14181. doi:10.1038/ncomms14181. PMID 28194018.
- ^ Cirillo, P; Gersch, MS; Mu, W; Scherer, PM; Kim, KM; Gesualdo, L; Henderson, GN; Johnson, RJ; Sautin, YY (March 2009). "Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells". Journal of the American Society of Nephrology : JASN. 20 (3): 545–53. doi:10.1681/ASN.2008060576. PMID 19158351.
- ^ Ishimoto, T; Lanaspa, MA; Rivard, CJ; Roncal-Jimenez, CA; Orlicky, DJ; Cicerchi, C; McMahan, RH; Abdelmalek, MF; Rosen, HR; Jackman, MR; MacLean, PS; Diggle, CP; Asipu, A; Inaba, S; Kosugi, T; Sato, W; Maruyama, S; Sánchez-Lozada, LG; Sautin, YY; Hill, JO; Bonthron, DT; Johnson, RJ (November 2013). "High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase". Hepatology (Baltimore, Md.). 58 (5): 1632–43. doi:10.1002/hep.26594. PMID 23813872.
- ^ Froesch, ER (November 1976). "Disorders of fructose metabolism". Clinics in endocrinology and metabolism. 5 (3): 599–611. doi:10.1016/s0300-595x(76)80042-4. PMID 189957.
It's evident from this draft that you are writing a term paper (NOTESSAY, NOTJOURNAL) rather than synthesizing established facts based on review articles. All your sources are primary research, not MEDRS reviews, and your text is a narrative of speculation (fine for a thesis or journal report) rather than review-established facts. Your text includes terms like "likely", "could be", "may also", "suggested", etc. which are not encyclopedic terms and facts. I suggest you spend some time absorbing MEDRS, MEDHOW, and WHYMEDRS to understand better the need for conclusive review sources, then write concise statements supported by high-quality reviews. Zefr (talk) 16:52, 2 March 2021 (UTC)
Your submission at Articles for creation: sandbox (April 30)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/7e/AFC-Logo_Decline.svg/50px-AFC-Logo_Decline.svg.png)
- If you would like to continue working on the submission, go to User:Pippin2k/sandbox and click on the "Edit" tab at the top of the window.
- If you now believe the draft cannot meet Wikipedia's standards or do not wish to progress it further, you may request deletion. Please go to User:Pippin2k/sandbox, click on the "Edit" tab at the top of the window, add "{{Db-g7}}" at the top of the draft text and click the blue "publish changes" button to save this edit.
- If you do not make any further changes to your draft, in 6 months, it will be considered abandoned and may be deleted.
- If you need any assistance, or have experienced any untoward behavior associated with this submission, you can ask for help at the Articles for creation help desk, on the reviewer's talk page or use Wikipedia's real-time chat help from experienced editors.
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Hello, Pippin2k!
Having an article declined at Articles for Creation can be disappointing. If you are wondering why your article submission was declined, please post a question at the Articles for creation help desk. If you have any other questions about your editing experience, we'd love to help you at the Teahouse, a friendly space on Wikipedia where experienced editors lend a hand to help new editors like yourself! See you there! DoubleGrazing (talk) 13:13, 30 April 2022 (UTC)
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- Please don't create multiple copies; you had submitted one for AfC review, and published another copy directly into the main space (incorrectly, IMO, as the referencing falls short of the required standard). --DoubleGrazing (talk) 13:15, 30 April 2022 (UTC)
Bernhard Landwehrmeyer moved to draftspace
An article you recently created, Bernhard Landwehrmeyer, is not suitable as written to remain published. It needs more citations from reliable, independent sources. (?) Information that can't be referenced should be removed (verifiability is of central importance on Wikipedia). I've moved your draft to draftspace (with a prefix of "Draft:
" before the article title) where you can incubate the article with minimal disruption. When you feel the article meets Wikipedia's general notability guideline and thus is ready for mainspace, please click on the "Submit your draft for review!" button at the top of the page. DoubleGrazing (talk) 13:21, 30 April 2022 (UTC)
- I have moved this article back into the draft space, because entire sections of it are unreferenced, which is problematic for any article, and especially so for articles on living people (see WP:BLP).
- Furthermore, two sections appear to have been copied or very closely paraphrased from external sources, without anything to indicate that a suitable licence to do so exists (and in any case, proper attribution is required). I will now go and delete the said content, and would invite you to rewrite the deleted sections in your own words.
- Thank you, -- DoubleGrazing (talk) 13:24, 30 April 2022 (UTC)
Your submission at Articles for creation: sandbox (May 1)
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/7e/AFC-Logo_Decline.svg/50px-AFC-Logo_Decline.svg.png)
- If you would like to continue working on the submission, go to User:Pippin2k/sandbox and click on the "Edit" tab at the top of the window.
- If you now believe the draft cannot meet Wikipedia's standards or do not wish to progress it further, you may request deletion. Please go to User:Pippin2k/sandbox, click on the "Edit" tab at the top of the window, add "{{Db-g7}}" at the top of the draft text and click the blue "publish changes" button to save this edit.
- If you do not make any further changes to your draft, in 6 months, it will be considered abandoned and may be deleted.
- If you need any assistance, or have experienced any untoward behavior associated with this submission, you can ask for help at the Articles for creation help desk, on the reviewer's talk page or use Wikipedia's real-time chat help from experienced editors.
May 2022
Your edit to Draft:Bernhard Landwehrmeyer has been removed in whole or in part, as it appears to have added copyrighted material to Wikipedia without evidence of permission from the copyright holder. If you are the copyright holder, please read Wikipedia:Donating copyrighted materials for more information on uploading your material to Wikipedia. For legal reasons, Wikipedia cannot accept copyrighted material, including text or images from print publications or from other websites, without an appropriate and verifiable license. All such contributions will be deleted. You may use external websites or publications as a source of information, but not as a source of content, such as sentences or images—you must write using your own words. Wikipedia takes copyright very seriously, and persistent violators of our copyright policy will be blocked from editing. See Wikipedia:Copying text from other sources for more information. — Diannaa (talk) 13:48, 2 May 2022 (UTC)
- Hello Diannaa, I have removed the copyright material until we our right to use it. Will you please lift the block if any? Pippin2k (talk) 14:12, 2 May 2022 (UTC)
Your review request on Draft:Bernhard Landwehrmeyer
Your message on my talk page:
Hello DoubleGrazing! I've amended the draft and added many sources, mainly from scientific journals where Prof. Landwehrmeyer is a author or contributor. I kindly ask you to review this article since it is important for him in his career advancement, which will benefit many patients with Huntington's disease, a rare, severe, debilitating disorder. — Preceding unsigned comment added by Pippin2k (talk • contribs) 14:20, 2 May 2022 (UTC) DoubleGrazing (talk) 14:35, 2 May 2022 (UTC)
- Thank you for moving the discussion here. How do I refer to you on my page so that you're notified about my request? Pippin2k (talk) 14:37, 2 May 2022 (UTC)