Article Evaluation

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  • The article is neutral and has no biased claims
  • The history about the marathon is under represented, and the history of trademarking the phrase is a bit over represented
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Article Selection

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Argpyrimidine

Carbamoyl phosphate

N(6)-Carboxymethyllysine

Aspartate ammonia-lyase

The research I'm involved in for my SRP is about Arginase deficiency, so I would love to edit an article that is related to Arginine metabolism, the urea cycle, or guanidino compounds so that I can further my understanding of the other mechanisms indirectly related to our disease.

-These all seem like good choices. Pick the one that interests you most. Make sure there is enough content to add as well. - Dr. Tienson-Tseng

References

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Argpyrimidine:

[1] :Argpyrimidine as biomarker for carbonyl stress

[2] :Argpyrimidine in diabetes

[3] : Argpyrimidine as tag in nanoparticle delivery for T2 Diabetes; talks about how it functions as a tag (therefore what it is involved in in the body and in disease)

[4] :argpyrimidine as Maillard rxn product

[5]: Maillard reaction, advanced glycation end products

[6] MG synthesis

[7] MG adduct in nuc of neuronal cells

[8] mapping MG and AP

[9]

Edit drafting:

Argpyrimidine is a fluorescent protein modification. This property of the methylglyoxal-mediated Maillard Reaction derivative has been studied for its potential as an indicator of diabetic proteins. ~[9]

Discussion Notes

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WP: REFB

WP: CITE

~5 sources by next week (10 for final)

wk4:

for next week: live edit on an article. Post at least a sentence (any article)

2 weeks from now first draft is due! (1-2 pages..)

=week6=

edit: Uncoupling Proteins; EMP3 (easy direct grammar edits on sandbox, everything else on talk pg)


Prepare powerpoint presentation and upload to ccle (due thurs of 10th week) (wiki dashboard has guidelines for presentation--focus on the science content added)

rest of quarter just edit drafts and work and rework

final draft due Dec 14 (live article "print out" as pdf onto ccle)

final reflection (letter to future seminar students--detail guidelines and rubric on ccle) and upload to ccle by Dec 14

Draft

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Synthesis

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Endogenous

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The pathways involved in the synthesis of Methylglyoxal, and subsequent production of Argpyrimidine.

In vivo, argpyrimidine is synthesized from a Methylglyoxal (MG) mediated modification on an arginine residue in a protein.[9] Methylglyoxal is formed through the Polyol pathway, the degradation of triose phosphates from Glycolysis, acetone metabolism, protein Glycation, or Lipid peroxidation.[1][6][9] Methylglyoxal then can modify Arginine, Cysteine, or Lysine amino acid residues within a protein.[9] The modification of these side chains through the Maillard reaction forms Advanced glycation end-products (AGEs).[7] This occurs when there is an increase in blood sugar levels in the body. The free sugar compounds undergo alternate pathways, like advanced glycation, to produce AGEs.[5] In the Methylglyoxal-mediated Maillard Reaction on arginine, a dihydroxy-imidazolidine intermediate is involved in the production of the argpyrimidine modification.[9]

 
Maillard reaction of argpyrimidine under physiological conditions[10]








Exogenous

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Mechanism of reductone intermediate formation from methylglyoxal in vitro. Two methylglyoxals undergo a Cannizzaro-like reaction initially to generate one methylglyoxal and one glyceraldehyde, then generate formic acid as a by-product through an intermolecular rearrangement.

In vitro, argpyrimidine has been synthesized through incubation with methylglyoxal and other higher sugars at physiological conditions.[9] In synthesis through other sugars, argpyrimidine was produced in lower concentrations with glyceraldehyde, threose, ribose, ascorbic acids, and glucose and fructose, respectively.[9] The argpyrimidine derivative produced through the MG-incubation with Nα-t-BOC-Arg (N-alpha-(tertbutoxycarbonyl)-L-Arginine), an alpha-amine protected amino acid derivative, in vitro used a reductone intermediate, 3-hydroxypentane-2,4-dione. This argpyrimidine product was found to be detectable by its blue fluorescent properties.[4][9]



 
General outline of the Maillard Reaction[11]

Argpyrimidine is also found in food chemistry through the browning of food by the Maillard Reaction. During this process, Glycation occurs, adding carbohydrate modifications to proteins and lipids.[5] By adding the sugar components to the food, there is an added/changed element to the flavor of the food. This reaction is involved in the formation of most yeast containing foods, including breads and fermented alcohols.[4]

The Maillard Reaction occurs between the carbonyl group of a sugar and the amino group on a protein. These react to form a N-substituted glycosylamine, also known as a Schiff base. The Schiff Base then undergoes an isomerization by an Amadori rearrangement to form a ketosamine, or a Amadori rearrangement. The Amadori product can then undergo many further reactions to form various AGE products, which can also be further modified into different products.[11]


Disease Research/Therapies

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Diabetes

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Argpyrimidine has been associated with Diabetes mellitus because of its relationship with Hyperglycemia in the body. Increased blood sugar is characteristic of Diabetes. During times of high concentration of sugar in the blood, the glucose-derivative methylglyoxal can be synthesized as an alternate pathway to glycolysis.[2] This then allows for the AGEs, like argpyrimidine, to be produced.[2] There have been studies that have linked the increase in AGEs to the characteristics of various diseases, including Diabetes, cardiovascular disease, and neurodegeneration.[2][5][7] Because of this, there has been increasing research regarding argpyrimidine's role in diabetes related injury.[1][7][12]

Aging

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Similar to its association with Diabetes, argpyrimidine is also a known biomarker for aging. Through glycation of certain proteins, Microglia and Macrophages are activated in the brain, leading to aging related diseases, such as Alzheimer's disease. This glycation due to increase in AGEs has also been linked to a release of Cytokines, and to the increase of Oxidative stress, which increases oxidative damage to DNA, proteins, and other macromolecules in the body.[5][12] The effects of the protein glycation is due to the interaction between the AGEs and their receptors on cell surfaces. Antioxidants have been shown to slow the process of aging and age related diseases by disrupting the interaction between AGEs and their receptors.[12][4]


Notes on Draft

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**Add more to Food chemistry section?

References

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  1. ^ a b c Ishida, Y. I.; Kayama, T.; Kibune, Y.; Nishimoto, S.; Koike, S.; Suzuki, T.; Horiuchi, Y.; Miyashita, M.; Itokawa, M. (11 04, 2017). "Identification of an argpyrimidine-modified protein in human red blood cells from schizophrenic patients: A possible biomarker for diseases involving carbonyl stress". Biochemical and Biophysical Research Communications. 493 (1): 573–577. doi:10.1016/j.bbrc.2017.08.150. ISSN 1090-2104. PMID 28867194. {{cite journal}}: Check date values in: |date= (help)
  2. ^ a b c d Flückiger, Rudolf; Cocuzzi, Enzo; Nagaraj, Ram H.; Shoham, Menachem; Kern, Timothy S.; Medof, M. Edward (01 2018). "DAF in diabetic patients is subject to glycation/inactivation at its active site residues". Molecular Immunology. 93: 246–252. doi:10.1016/j.molimm.2017.06.036. ISSN 1872-9142. PMC 5884443. PMID 28886871. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  3. ^ Bhattacherjee, Abhishek; Chakraborti, Abhay Sankar (2017-08-07). "Argpyrimidine-tagged rutin-encapsulated biocompatible (ethylene glycol dimers) nanoparticles: Application for targeted drug delivery in experimental diabetes (Part 2)". International Journal of Pharmaceutics. 528 (1–2): 8–17. doi:10.1016/j.ijpharm.2017.05.058. ISSN 1873-3476. PMID 28559218.
  4. ^ a b c d Bhattacherjee, Abhishek; Dhara, Kaliprasanna; Chakraborti, Abhay Sankar (2017-9). "Bimolecular interaction of argpyrimidine (a Maillard reaction product) in in vitro non-enzymatic protein glycation model and its potential role as an antiglycating agent". International Journal of Biological Macromolecules. 102: 1274–1285. doi:10.1016/j.ijbiomac.2017.04.108. ISSN 1879-0003. PMID 28487198. {{cite journal}}: Check date values in: |date= (help)
  5. ^ a b c d e Ahern, Kevin; Rajagopal, Indira; Tan, Taralyn (2016). Biochemistry Free and For All. NC-Creative Commons. pp. 204–207.
  6. ^ a b Desai, Kaushik M.; Chang, Tuanjie; Wang, Hui; Banigesh, Ali; Dhar, Arti; Liu, Jianghai; Untereiner, Ashley; Wu, Lingyun (2010-03). "Oxidative stress and aging: Is methylglyoxal the hidden enemy?This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease". Canadian Journal of Physiology and Pharmacology. 88 (3): 273–284. doi:10.1139/y10-001. ISSN 0008-4212. {{cite journal}}: Check date values in: |date= (help)
  7. ^ a b c d "The formation of argpyrimidine, a methylglyoxal–arginine adduct, in the nucleus of neural cells". Biochemical and Biophysical Research Communications. 378 (2): 209–212. 2009-01-09. doi:10.1016/j.bbrc.2008.11.028. ISSN 0006-291X.
  8. ^ "Bimolecular interaction of argpyrimidine (a Maillard reaction product) in in vitro non-enzymatic protein glycation model and its potential role as an antiglycating agent". International Journal of Biological Macromolecules. 102: 1274–1285. 2017-09-01. doi:10.1016/j.ijbiomac.2017.04.108. ISSN 0141-8130.
  9. ^ a b c d e f g h i The Maillard reaction in foods and medicine. O'Brien, John, 1960 May 26-. Cambridge: Woodhead Publishing Ltd. 1998. ISBN 9781845698447. OCLC 798340515.{{cite book}}: CS1 maint: others (link)
  10. ^ Henning, Christian; Glomb, Marcus A. (2016-06-13). "Pathways of the Maillard reaction under physiological conditions". Glycoconjugate Journal. 33 (4): 499–512. doi:10.1007/s10719-016-9694-y. ISSN 0282-0080.
  11. ^ a b "Food Chemistry – The Maillard Reaction | Compound Interest". Compound Interest. 2015-01-27. Retrieved 2018-12-01.
  12. ^ a b c Younessi, Parisa; Yoonessi, Ali (2011-9). "Advanced Glycation End-Products and Their Receptor-Mediated Roles: Inflammation and Oxidative Stress". Iranian Journal of Medical Sciences. 36 (3): 154–166. ISSN 0253-0716. PMC 3556769. PMID 23358382. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)