Peer Review - Marissa Ogata
For the first picture of the protein structure of malate dehydrogenase, it would be beneficial to state which colors represent the protein itself and which proteins represent the cofactors. A very small grammatical thing I noticed is consistency with spelling. For example, when spelling catalyze, try sticking to one spelling (catalyze, catalyse). I think that you can expand on the kinetics section of the page. The figure/picture is good, but I think it would be beneficial to give a more in depth explanation of how this reaction works, so try to expand a little on this section. Furthermore, in the "Allosteric regulation section" possibly link the page for alpha ketogluturate dehydrogenase to the word. I really like the glycolysis/gluconeogenesis figure as well. Overall you did a great job and there are only some minor changes that I think should be made.
Article Topic: Malate Dehydrogenase
Malate dehydrogenase is one of the enzymes that participate in the Citric Acid Cycle and is responsible for conversion of malate to oxaloacetate and reducing NAD+ electron carrier. I would like to learn more about and research the kinetics and mechanism of the reaction involved. Specifically, I will research more on the kinetics involved in the reaction catalyzed by malate dehydrogenase[1] and also the catalytic mechanism of malate dehydrogenase[2]. I could also add a diagram showing the reaction of the enzyme with substrate. I also plan on studying and adding to the article about the role of malate dehydrogenase in the citric acid and its interactions with citrate synthase and other enzymes involved in the citric acid cycle[3][4][5]. Additionally, I can also add more information about regulation of malate dehydrogenase[6]. Another thing I can write and add to the article are the isozymes of malate dehydrogenase[7].
Mechanism of Malate Dehydrogenase is pH Dependent
Malate dehydrogenase interaction with substrate is mediated and dependent on pH level. When malate dehydrogenase binds to oxaloacetate and coenzymes to form a complex, a higher pH is required. Formation of MDH-NADH complex with binding of L-malate requires a higher pH and a histidine moiety on the MDH. Specifically, the protonated histidine can form a hydrogen bond with the substrate's carbonyl oxygen, which shifts electron density away from the oxygen and makes it more susceptible to nucleophilic attack by hydride. As a result, the unprotonated form the MDH-NADH complex binds more favorably to L-malate. In contrast, binding of D-malate and hydroxymalonate to MDH-NADH complex requires a lower pH. Additionally, the protonated form of MDH-NADH complex has a higher affinity for D-malate and hydroxymalonate. [1]
A More Detailed Mechanism of Malate Dehydrogenase
The substate malate is oriented to the active site of malate dehydrogenase in such a way that the hydrogen bonding between malate's carboxylate oxygen atom and the guanidinium functional groups on the sides chains of Arg-81 and Arg-153 on MDH help to stabilize and facilitate the proton and hydride transfer between the substrate and enzyme. These hydrogen bonds remain constant throughout the process. The catalytic mechanism is described as sequential, with the transfer of proton from malate to malate dehydrogenase occurring before the the hydride transfer from malate to NAD+, resulting in the formation of NADH. [8]
I should also include a diagram depicting the catalytic mechanism.
I should also include a diagram showing the general reaction catalyzed by malate dehydrogenase.
Malate + NAD -> NADH + Oxaloacetate
More Details on Regulation of Malate Dehydrogenase
Glutamate has been shown to inhibit malate dehydrogenase activity. Furthermore, it has been shown that alpha ketogluturate dehydrogenase can interact with mitochondrial aspartate aminotransferase to form a complex, which can then bind to malate dehydrogenase, forming a ternary complex that reverses inhibitory action on malate dehydrogenase enzymatic activity by glutamate. [6]Additionally, the formation of this complex enables glutatmate to react with aminotransferase without interfering activity of malate dehydrogenase. The binding of malate dehydrogenase has been shown to increase reaction rate because the Km of malate dehydrogenase is decreased when bound as part of this complex.
I should try to synthesize these findings to the article's discussion of citrate as allosteric inhibitor.
Additional sources:
Malate dehydrogenase[9]
dehydrogenase[10]
dehydrogenase[11]
dehydrogenase[1]
Death folds are involved in protein cell death processes such as apoptosis. I would like to learn more about and research how do death folds in protein structure participate in apoptosis and the mechanism. Death fold
Citrate synthase is the enzyme responsible for the recycling of the 4 carbon molecule to 6 carbon molecule. I would like to know and research about the function, kinetics (since it sets the pace of the citric acid cycle), and mechanism. Citrate synthase
NTP Binding Site
| This user is a student editor in Wikipedia:Wiki_Ed/UCLA/Chem_153A_Honors_(Winter_2017). Student assignments should always be carried out using a course page set up by the instructor. It is usually best to develop assignments in your sandbox. After evaluation, the additions may go on to become a Wikipedia article or be published in an existing article. |
- ^ a b c Dasika, Santosh K.; Vinnakota, Kalyan C.; Beard, Daniel A. (2015-01-20). "Determination of the Catalytic Mechanism for Mitochondrial Malate Dehydrogenase". Biophysical Journal. 108 (2): 408–419. doi:10.1016/j.bpj.2014.11.3467. ISSN 0006-3495. PMC 4302198. PMID 25606688.
{{cite journal}}: no-break space character in|first2=at position 7 (help); no-break space character in|first3=at position 7 (help); no-break space character in|first=at position 8 (help)CS1 maint: PMC format (link) - ^ Bernstein, L. H.; Everse, J. (1978-12-25). "Studies on the mechanism of the malate dehydrogenase reaction". The Journal of Biological Chemistry. 253 (24): 8702–8707. ISSN 0021-9258. PMID 31361.
- ^ Tompa, P.; Batke, J.; Ovadi, J.; Welch, G. R.; Srere, P. A. (1987-05-05). "Quantitation of the interaction between citrate synthase and malate dehydrogenase". The Journal of Biological Chemistry. 262 (13): 6089–6092. ISSN 0021-9258. PMID 3571248.
- ^ Beeckmans, S.; Kanarek, L. (1981-07-01). "Demonstration of physical interactions between consecutive enzymes of the citric acid cycle and of the aspartate-malate shuttle. A study involving fumarase, malate dehydrogenase, citrate synthesis and aspartate aminotransferase". European Journal of Biochemistry. 117 (3): 527–535. ISSN 0014-2956. PMID 7285903.
- ^ Datta, A.; Merz, J. M.; Spivey, H. O. (1985-12-05). "Substrate channeling of oxalacetate in solid-state complexes of malate dehydrogenase and citrate synthase". The Journal of Biological Chemistry. 260 (28): 15008–15012. ISSN 0021-9258. PMID 4066662.
- ^ a b Fahien, L. A.; Kmiotek, E. H.; MacDonald, M. J.; Fibich, B.; Mandic, M. (1988-08-05). "Regulation of malate dehydrogenase activity by glutamate, citrate, alpha-ketoglutarate, and multienzyme interaction". The Journal of Biological Chemistry. 263 (22): 10687–10697. ISSN 0021-9258. PMID 2899080.
- ^ Meizel, Stanley; Markert, Clement L. (1967-12-01). "Malate dehydrogenase isozymes of the marine snail, Ilyanassa obsoleta". Archives of Biochemistry and Biophysics. 122 (3): 753–765. doi:10.1016/0003-9861(67)90185-3.
- ^ Cunningham, Mark A.; Ho, L. Lawrence; Nguyen, Dzung T.; Gillilan, Richard E.; Bash, Paul A. (1997-04-01). "Simulation of the Enzyme Reaction Mechanism of Malate Dehydrogenase". Biochemistry. 36 (16): 4800–4816. doi:10.1021/bi962734n. ISSN 0006-2960.
- ^ Tesfaye, Mesfin; Temple, Stephen J.; Allan, Deborah L.; Vance, Carroll P.; Samac, Deborah A. (2001-12-01). "Overexpression of Malate Dehydrogenase in Transgenic Alfalfa Enhances Organic Acid Synthesis and Confers Tolerance to Aluminum". Plant Physiology. 127 (4): 1836–1844. doi:10.1104/pp.010376. ISSN 1532-2548. PMID 11743127.
- ^ Goward, Christopher R.; Nicholls, David J. (1994-10-01). "Malate dehydrogenase: A model for structure, evolution, and catalysis". Protein Science. 3 (10): 1883–1888. doi:10.1002/pro.5560031027. ISSN 1469-896X. PMC 2142602. PMID 7849603.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Gelpí, J L; Dordal, A; Montserrat, J; Mazo, A; Cortés, A (1992-04-01). "Kinetic studies of the regulation of mitochondrial malate dehydrogenase by citrate". Biochemical Journal. 283 (Pt 1): 289–297. ISSN 0264-6021. PMC 1131027. PMID 1567375.
{{cite journal}}: CS1 maint: PMC format (link)