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Reflection and Course comments

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While critiquing the articles I learn that there is a strong emphasis on using facts and having sources to support those facts. After critiquing the other wikipedia articles I was more aware about looking for facts supported by a reliable source. As for my approach when critiquing the article I chose, I would try to be conscious about whether the facts stated have a citation from a reliable source and I would also try to see if the paragraph made sense and that the subject being covered is easy to understand. I saw the regulation section of the lipogenesis article was lacking and decided that I would like to focus on that section since I could find some good resources about it. The sections that I included talked about how the body manages to mediated the lipogenesis process through the use of various hormones. The transcriptional regulation section takes a look at how certain conditions and hormones affects transcriptional regulators that mediate the lipogenesis process. I thought that by adding of the hormonal and transcriptional regulation there would be a better understanding about the biochemistry behind lipogenesis and how the body manages to control this process. As compared to the previous article I feel that the changes made give an understanding about how some parts of the lipogenesis process takes place. For the peer review process I looked at the articles about the urea cycle and ketogenesis. For the the article about the urea cycle I like the layout used to write about the steps involved in the urea cycle. I noticed that there weren’t many citations included but I wasn’t sure if they were going to be added later, however I still mentioned it in my comments. For the ketogenesis article I had also noticed that there weren’t many citations and I had also mentioned that on the writer’s sandbox. The edits to the article looked good and were simple to understand. The comments left from my peer reviewer mentioned that there some paragraphs could have more added. I took the comment to consideration however I couldn’t find as much information as I wanted to. There was also some grammatical corrections which I implemented. As for wikipedia editors outside the class, I didn’t get any feedback in my sandbox. From editing the article I learnt that being sure about the facts and their sources are incredibly important. As compared to other assignments I felt that the wikipedia article puts my work on a public platform where it can experience more scrutiny and so I had to be more cautious about what I have written. That being said, the wikipedia article also gave me the opportunity to express a what I have learnt to a more general audience. Through the method of having people who are interested and learned in a certain field writing about a subject in an engaging manner that is easier to understand, wikipedia can be used to improve public understanding of a field or topic. The information presented to the public may be helpful to the general audience that do not necessarily have the resource to study the topic themselves but it also helps the writer as more people may take an interest in the field which could lead to more public recognition and understanding about the importance and impact of the field.

Comments about using Wikipedia

I felt that the information on how not to plagiarize and how to write an article is redundant as we have learnt that while writing papers for our other classes. I would have liked to see more information about the editing process as it was not as intuitive as the program made it out to be. In the future having clearer instructions would also be more helpful because I wasn’t sure which spaces I should be doing certain tasks. One example is the peer review where I was unsure about putting the comments on the other person's page or on my page so my professor would know that I had done the assigned peer review.

Draft: lipogenesis

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Lipogenesis is the process by which acetyl-CoA is converted to fatty acids. The former is an intermediate stage in metabolism of simple sugars, such as glucose, a source of energy of living organisms. Through lipogenesis and subsequent triglyceride synthesis, the energy can be efficiently stored in the form of fats.

Lipogenesis encompasses both the process of fatty acid synthesis and triglyceride synthesis (where fatty acids are esterified to glycerol).[1] The products are secreted from the liver in the form of very-low-density lipoproteins (VLDL). VLDL particles are secreted directly into blood, where they mature and function to deliver the endogenously derived lipids to peripheral tissues.

Fatty acid synthesis

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Main article: Fatty acid synthesis

Fatty acids synthesis starts with acetyl-CoA and builds up by the addition of two-carbon units. The synthesis occurs in the cytoplasm of the cell, in contrast to the degradation (oxidation), which occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthase.[2] The major sites of fatty acid synthesis are adipose tissue and the liver.[3]

Control and regulation

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Insulin is a peptide hormone that is critical for managing the body's metabolism. Insulin is released by the pancreas when blood sugar levels rise, and it has many effects that broadly promote the absorption and storage of sugars, including lipogenesis.

Insulin stimulates lipogenesis primarily by activating two enzymatic pathways. Pyruvate dehydrogenase (PDH), converts pyruvate into acetyl-CoA. Acetyl-CoA carboxylase (ACC), converts acetyl-CoA produced by PDH into malonyl-CoA. Malonyl-CoA provides the two-carbon building blocks that are used to create larger fatty acids. [not sure if I can remove these sentences, I'll probably check with Kelly first]

Hormonal regulation

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Insulin is hypothesized to stimulate lipogenesis [4]. The mode of stimulation occurs through the promotion of glucose uptake by adipose tissue. The increase in the uptake of glucose can occur through the use of glucose transporters directed to the plasma membrane or through the activation of lipogenic and glycolytic enzymes via covalent modification[5]. The hormone has also been found to have long term effects on lipogenic gene expression. It is hypothesized that this effect occurs through the transcription factor SREBP-1, where the association of insulin and SREBP-1 lead to the gene expression of glucokinase[6]. The interaction of glucose and lipogenic gene expression is assumed to be managed by the increasing concentration of an unknown glucose metabolite through the activity of glucokinase[4].

Another hormone that may affects lipogenesis through the SREBP-1 pathway is leptin. It is involved in the process by limiting fat storage through inhibition of glucose intake and interfering with other adipose metabolic pathways[4]. The inhibition of lipogenesis occurs through the down regulation of fatty acid and triglyceride gene expression[7]. Through the promotion of fatty acid oxidation and lipogenesis inhibition, leptin was found to control the release of stored glucose from adipose tissues[4].

Other hormones that prevent the stimulation of lipogenesis in adipose cells are growth hormones (GH). Growth hormones result in loss of fat but stimulates muscle gain[8]. One proposed mechanism for how the hormone works is that growth hormones affects insulin signaling thereby decreasing insulin sensitivity and in turn down regulating fatty acid synthase expression[9]. Another proposed mechanism suggests that growth hormones may phosphorylate with STAT5A and STAT5B, transcription factors that are a part of the Signal Transducer And Activator Of Transcription (STAT) family[10].

There is also evidence suggesting that acylation stimulating protein (ASP) promotes the aggregation of triglycerides in adipose cells[11]. This aggregation of triglycerides occurs through the increase in the synthesis of triglyceride production[12].

Transcriptional regulation

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SREBPs have been found to play a role with the nutritional or hormonal effects on the lipogenic gene expression [13]. SREBP-2 has a well defined mode of action of the different members of this transcriptional family. At high levels of free cholesterol in the cell SREBP-2 is found bound to the endoplasmic reticulum as an immature precursor. when the level of cholesterol drops then the SREBP-2 is proteolytically cleaved releasing the mature fragment so it can move to the nucleus and bind to the sterol response element in the promoter region of target genes. These genes are then activated for transcription [1].

It has been indicated that SREBP-2 promote the expression of genes involved in cholesterol metabolism in liver cells [1]. It has been indicated that SREBP-1 plays a role in the activation of genes connected with lipogenesis in liver. Studies have found that an over expression of SREBP-1a or SREBP-1c in mouse liver cells results in the build-up of hepatic triglycerides and higher expression levels of lipogenic genes [14].

Lipogenic gene expression in the liver via glucose and insulin is moderated by SREBP-1[15] . The effect of glucose and insulin on the transcriptional factor can occur through various pathways [1]. There is evidence suggesting that insulin promotes SREBP-1 mRNA expression in adipocytes [16] and hepatocytes [17] , it has also been suggested that the hormone increases transcriptional activation by SREBP-1 through MAP-kinase-dependent phosphorylation regardless of changes in the mRNA levels[18]. Along with insulin glucose also have been shown to promote SREBP-1 activity and mRNA expression[19].

PDH dephosphorylation

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Insulin stimulates the activity of pyruvate dehydrogenase phosphatase. The phosphatase removes the phosphate from pyruvate dehydrogenase activating it and allowing for conversion of pyruvate to acetyl-CoA. This mechanism leads to the increased rate of catalysis of this enzyme, so increases the levels of acetyl-CoA. Increased levels of acetyl-CoA will increase the flux through not only the fat synthesis pathway but also the citric acid cycle.

Acetyl-CoA carboxylase

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Main article: Acetyl-CoA carboxylase

Insulin affects ACC in a similar way to PDH. It leads to its dephosphorylation via activation of PP2A phosphatase whose activity results in the activation of the enzyme. Glucagon has an antagonistic effect and increases phosphorylation, deactivation, thereby inhibiting ACC and slowing fat synthesis.

Affecting ACC affects the rate of acetyl-CoA conversion to malonyl-CoA. Increased malonyl-CoA level pushes the equilibrium over to increase production of fatty acids through biosynthesis. Long chain fatty acids are negative allosteric regulators of ACC and so when the cell has sufficient long chain fatty acids, they will eventually inhibit ACC activity and stop fatty acid synthesis.

AMP and ATP concentrations of the cell act as a measure of the ATP needs of a cell. When ATP is depleted, there is a rise in 5'AMP. This rise activates AMP-activated protein kinase, which phosphorylates ACC and thereby inhibits fat synthesis. This is a useful way to ensure that glucose is not diverted down a storage pathway in times when energy levels are low.

ACC is also activated by citrate. When there is abundant acetyl-CoA in the cell cytoplasm for fat synthesis, it proceeds at an appropriate rate.

Note: Research now shows that glucose metabolism (exact metabolite to be determined), aside from insulin's influence on lipogenic enzyme genes, can induce the gene products for liver's pyruvate kinase, acetyl-CoA carboxylase, and fatty acid synthase. These genes are induced by the transcription factors ChREBP/Mlx via high blood glucose levels[20] and presently unknown signaling events. Insulin induction of SREBP-1c is also involved in cholesterol metabolism.

(There is a paragraph about Fatty acid esterification on the main article but I thought it would be best to remove it as it serves no purpose and it just a copy from the abstract of the reference Karmen, Arthur; Whyte, Malcolm; Goodman, DeWitt S. (July 1963). "Fatty acid esterification and chylomicron formation during fat absorption: 1. Triglycerides and cholesterol esters". The Journal of Lipid Research. 4: 312–321. PMID 14168169. Retrieved 24 August 2013.)  

In industry

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About 100,000 metric tons of the natural fatty acids are consumed in the preparation of various fatty acid esters.[citation needed] The simple esters with lower chain alcohols (methyl-, ethyl-, n-propyl-, isopropyl- and butyl esters) are used as emollients in cosmetics and other personal care products and as lubricants. Esters of fatty acids with more complex alcohols, such as sorbitol, ethylene glycol, diethylene glycol, and polyethylene glycol are consumed in foods, personal care, paper, water treatment, metal working fluids, rolling oils, and synthetic lubricants.

References

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  1. ^ a b c d Kersten S (April 2001). "Mechanisms of nutritional and hormonal regulation of lipogenesis". EMBO Rep. 2 (4): 282–6. doi:10.1093/embo-reports/kve071. PMC 1083868. PMID 11306547.
  2. ^ Elmhurst College. "Lipogenesis". Retrieved 2007-12-22.
  3. ^ J. Pearce (1983). "Fatty acid synthesis in liver and adipose tissue". Proceedings of the Nutrition Society. 2: 263–271. doi:10.1079/PNS19830031.
  4. ^ a b c d Cite error: The named reference :0 was invoked but never defined (see the help page).
  5. ^ Cite error: The named reference :1 was invoked but never defined (see the help page).
  6. ^ Cite error: The named reference :2 was invoked but never defined (see the help page).
  7. ^ Cite error: The named reference :3 was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference :4 was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference :5 was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference :6 was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference :7 was invoked but never defined (see the help page).
  12. ^ Cite error: The named reference :8 was invoked but never defined (see the help page).
  13. ^ Hua, X; Yokoyama, C; Wu, J; Briggs, M R; Brown, M S; Goldstein, J L; Wang, X (1993-12-15). "SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element". Proceedings of the National Academy of Sciences of the United States of America. 90 (24): 11603–11607. ISSN 0027-8424. PMC 48032. PMID 7903453.{{cite journal}}: CS1 maint: PMC format (link)
  14. ^ Horton, J. D.; Shimomura, I. (1999-04-01). "Sterol regulatory element-binding proteins: activators of cholesterol and fatty acid biosynthesis". Current Opinion in Lipidology. 10 (2): 143–150. ISSN 0957-9672. PMID 10327282.
  15. ^ Shimano, H.; Yahagi, N.; Amemiya-Kudo, M.; Hasty, A. H.; Osuga, J.; Tamura, Y.; Shionoiri, F.; Iizuka, Y.; Ohashi, K. (1999-12-10). "Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes". The Journal of Biological Chemistry. 274 (50): 35832–35839. ISSN 0021-9258. PMID 10585467.
  16. ^ Kim, J B; Sarraf, P; Wright, M; Yao, K M; Mueller, E; Solanes, G; Lowell, B B; Spiegelman, B M (1998-01-01). "Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1". Journal of Clinical Investigation. 101 (1): 1–9. doi:10.1172/JCI1411. ISSN 0021-9738. PMC 508533. PMID 9421459.{{cite journal}}: CS1 maint: PMC format (link)
  17. ^ Foretz, Marc; Pacot, Corinne; Dugail, Isabelle; Lemarchand, Patricia; Guichard, Colette; le Lièpvre, Xavier; Berthelier-Lubrano, Cécile; Spiegelman, Bruce; Kim, Jae Bum (1999-05-01). "ADD1/SREBP-1c Is Required in the Activation of Hepatic Lipogenic Gene Expression by Glucose". Molecular and Cellular Biology. 19 (5): 3760–3768. ISSN 0270-7306. PMC 84202. PMID 10207099.{{cite journal}}: CS1 maint: PMC format (link)
  18. ^ Roth, G.; Kotzka, J.; Kremer, L.; Lehr, S.; Lohaus, C.; Meyer, H. E.; Krone, W.; Müller-Wieland, D. (2000-10-27). "MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein (SREBP)-1a at serine 117 in vitro". The Journal of Biological Chemistry. 275 (43): 33302–33307. doi:10.1074/jbc.M005425200. ISSN 0021-9258. PMID 10915800.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ Hasty, A. H.; Shimano, H.; Yahagi, N.; Amemiya-Kudo, M.; Perrey, S.; Yoshikawa, T.; Osuga, J.; Okazaki, H.; Tamura, Y. (2000-10-06). "Sterol regulatory element-binding protein-1 is regulated by glucose at the transcriptional level". The Journal of Biological Chemistry. 275 (40): 31069–31077. doi:10.1074/jbc.M003335200. ISSN 0021-9258. PMID 10913129.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  20. ^ Work from Howard Towle, Catherine Postic, and K. Uyeda.

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Draft lipogenesis: Hormonal regulation

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Hormonal regulation

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Insulin is hypothesized to stimulate lipogenesis [you should support this hypothesis with a reference]. The mode of stimulation occurs through the promotion of glucose uptake by adipose tissue by [did you mean to have another "by" here?]. Increase in the uptake of glucose can happen through the use of glucose transporters directed to the plasma membrane or through the activation of lipogenic and glycolytic enzymes through covalent modification [starting this sentence with a verb sounds a bit odd when saying it aloud]. The hormone has also been found to have long term effects on lipogenic gene expression. It is hypothesized that this effect occurs through the transcription factor SREBP-1, where the association of insulin and SREBP-1 lead to the gene expression of glucokinase [another reference if possible]. The interaction of glucose and lipogenic gene expression is assumed to be managed by the increasing concentration of an unknown glucose metabolite through the activity of glucokinase[1][2][3]. [I would place the references to where they are directly cited]

Another hormone that may affects the SREBP-1 pathway is leptin. Leptin has been found to also play a role in lipogenesis [this sentence seems a bit redundant]. It is involved in the process by limiting fat storage through inhibition of glucose intake and interfering with other adipose metabolic pathways[3]. The inhibition of lipogenesis occurs through the down regulation of fatty acid and triglyceride gene expression[4]. Through the promotion of fatty acid oxidation and lipogenesis inhibition, leptin was found to control the release of stored glucose from adipose tissues[3].

Other hormones that prevents [prevent] the stimulation of lipogenesis in adipose cells are growth hormones (GH). Growth hormones result in loss of fat but stimulates muscle gain[5]. One proposed mechanism for how the hormone works is that growth hormones affects insulin signaling thereby decreasing insulin sensitivity and in turn down regulating fatty acid synthase expression[6]. Another proposed mechanism suggests that growth hormones may phosphorylate with STAT5A and STAT5B, transcription factors that are a part of the Signal Transducer And Activator Of Transcription (STAT) family[7].

There is also evidence suggesting that acylation stimulating protein (ASP) promotes the aggregation of triglycerides in adipose cells[8]. This aggregation of triglycerides occurs through the increase in the synthesis of triglyceride production[9].

You go into a great amount of detail for insulin regulation of lipogenesis. Would it be possible to also go into as much detail for the leptin and, GH, and ASP hormones also? Those seem a bit weaker compared to the insulin paragraph. All in all it is really good though! - Matt

There doesn't seem to be much information out there but I'll keep looking!-A

Majumak (talk) 07:30, 6 April 2017 (UTC)


For the Lipogenesis article I noticed that there was a lack of citations. I will probably have to go through some articles, especially those listed in the citations section and start my search about the topic from there. I also want to start of by looking at the reviews- Mechanisms of nutritional and hormonal regulation of lipogenesis (Sander Kersten, 2001) and De novo lipogenesis in health and disease (Ameer. F. et al, 2014). I would probably want to work on the control and regulation section as there seems to be literature about the topic. Majumak (talk) 19:39, 24 March 2017 (UTC)

  1. ^ Assimacopoulos-Jeannet, F.; Brichard, S.; Rencurel, F.; Cusin, I.; Jeanrenaud, B. (1995-02-01). "In vivo effects of hyperinsulinemia on lipogenic enzymes and glucose transporter expression in rat liver and adipose tissues". Metabolism: Clinical and Experimental. 44 (2): 228–233. ISSN 0026-0495. PMID 7869920.
  2. ^ Foretz, M.; Guichard, C.; Ferré, P.; Foufelle, F. (1999-10-26). "Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes". Proceedings of the National Academy of Sciences of the United States of America. 96 (22): 12737–12742. ISSN 0027-8424. PMC 23076. PMID 10535992.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ a b c Kersten, Sander (2001-04-15). "Mechanisms of nutritional and hormonal regulation of lipogenesis". EMBO Reports. 2 (4): 282–286. doi:10.1093/embo-reports/kve071. ISSN 1469-221X. PMC 1083868. PMID 11306547.{{cite journal}}: CS1 maint: PMC format (link)
  4. ^ Soukas, A.; Cohen, P.; Socci, N. D.; Friedman, J. M. (2000-04-15). "Leptin-specific patterns of gene expression in white adipose tissue". Genes & Development. 14 (8): 963–980. ISSN 0890-9369. PMC 316534. PMID 10783168.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ Etherton, T. D. (2000-11-01). "The biology of somatotropin in adipose tissue growth and nutrient partitioning". The Journal of Nutrition. 130 (11): 2623–2625. ISSN 0022-3166. PMID 11053496.
  6. ^ Yin, D.; Clarke, S. D.; Peters, J. L.; Etherton, T. D. (1998-05-01). "Somatotropin-dependent decrease in fatty acid synthase mRNA abundance in 3T3-F442A adipocytes is the result of a decrease in both gene transcription and mRNA stability". The Biochemical Journal. 331 ( Pt 3): 815–820. ISSN 0264-6021. PMC 1219422. PMID 9560309.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ Teglund, S.; McKay, C.; Schuetz, E.; van Deursen, J. M.; Stravopodis, D.; Wang, D.; Brown, M.; Bodner, S.; Grosveld, G. (1998-05-29). "Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses". Cell. 93 (5): 841–850. ISSN 0092-8674. PMID 9630227.
  8. ^ Sniderman, A. D.; Maslowska, M.; Cianflone, K. (2000-06-01). "Of mice and men (and women) and the acylation-stimulating protein pathway". Current Opinion in Lipidology. 11 (3): 291–296. ISSN 0957-9672. PMID 10882345.
  9. ^ Murray, I.; Sniderman, A. D.; Cianflone, K. (1999-09-01). "Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice". The American Journal of Physiology. 277 (3 Pt 1): E474–480. ISSN 0002-9513. PMID 10484359.
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