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1

Schofield, J. P. "Molecular studies on an ancient gene encoding for carbamoyl-phosphate synthetase." Clinical Science 84, no. 2 (1993): 119–28. http://dx.doi.org/10.1042/cs0840119.

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1. Carbamoyl-phosphate synthetase (EC 6.3.5.5.) catalyses the synthesis of carbamoyl phosphate, the immediate precursor of arginine and pyrimidine biosynthesis, and is highly conserved throughout evolution. The large subunit of all carbamoyl-phosphate synthetases sequenced to date comprises two highly homologous halves, the product of a proposed ancestral gene duplication. The sequences of the enzymes of Escherichia coli, Drosophila melanogaster, Saccharomyces cerevisiae, rat and Syrian hamster all have duplications, suggesting that this event occurred in the progenote predating the separation
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2

Thoden, James B., Xinyi Huang, Frank M. Raushel, and Hazel M. Holden. "Carbamoyl-phosphate Synthetase." Journal of Biological Chemistry 277, no. 42 (2002): 39722–27. http://dx.doi.org/10.1074/jbc.m206915200.

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3

Anderson, P. M. "Glutamine-dependent carbamoyl-phosphate synthetase and other enzyme activities related to the pyrimidine pathway in spleen of Squalus acanthias (spiny dogfish)." Biochemical Journal 261, no. 2 (1989): 523–29. http://dx.doi.org/10.1042/bj2610523.

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The first two steps of urea synthesis in liver of marine elasmobranchs involve formation of glutamine from ammonia and of carbamoyl phosphate from glutamine, catalysed by glutamine synthetase and carbamoyl-phosphate synthetase, respectively [Anderson & Casey (1984) J. Biol. Chem. 259, 456-462]; both of these enzymes are localized exclusively in the mitochondrial matrix. The objective of this study was to establish the enzymology of carbamoyl phosphate formation and utilization for pyrimidine nucleotide biosynthesis in Squalus acanthias (spiny dogfish), a representative elasmobranch. Aspart
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4

Guy, Hedeel I., Anne Bouvier, and David R. Evans. "The Smallest Carbamoyl-phosphate Synthetase." Journal of Biological Chemistry 272, no. 46 (1997): 29255–62. http://dx.doi.org/10.1074/jbc.272.46.29255.

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5

Husson, A., M. Bouazza, C. Buquet, and R. Vaillant. "Role of dexamethasone and insulin on the development of the five urea-cycle enzymes in cultured rat foetal hepatocytes." Biochemical Journal 225, no. 1 (1985): 271–74. http://dx.doi.org/10.1042/bj2250271.

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The activity changes of the urea-cycle enzymes were monitored in cultured foetal hepatocytes after dexamethasone and insulin treatments. Addition of dexamethasone induced the development of carbamoyl-phosphate synthetase, argininosuccinate synthetase, argininosuccinase and arginase activities as soon as day 16.5 of gestation. When insulin was added together with dexamethasone, it markedly inhibited the steroid-induced increase in carbamoyl-phosphate synthetase, argininosuccinate synthetase and argininosuccinase activities.
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6

Braxton, B. L., Leisha S. Mullins, Frank M. Raushel, and Gregory D. Reinhart. "Allosteric Dominance in Carbamoyl Phosphate Synthetase†." Biochemistry 38, no. 5 (1999): 1394–401. http://dx.doi.org/10.1021/bi982097w.

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7

Nara, Takeshi, Ganghan Gao, Hiroshi Yamasaki, Junko Nakajima-Shimada, and Takashi Aoki. "Carbamoyl-phosphate synthetase II in kinetoplastids." Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 1387, no. 1-2 (1998): 462–68. http://dx.doi.org/10.1016/s0167-4838(98)00127-7.

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8

Martinez-Ramon, A., E. Knecht, V. Rubio, and S. Grisolia. "Levels of carbamoyl phosphate synthetase I in livers of young and old rats assessed by activity and immunoassays and by electron microscopic immunogold procedures." Journal of Histochemistry & Cytochemistry 38, no. 3 (1990): 371–76. http://dx.doi.org/10.1177/38.3.2303702.

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Carbamoyl phosphate synthetase I, the most abundant protein of rat liver mitochondria, plays a key role in synthesis of urea. Because aging affects some liver functions, and because there is no information on the levels of carbamoyl phosphate synthetase I during aging, we assayed the activity of this enzyme and determined immunologically the level of carbamoyl phosphate synthetase I in liver homogenates from young (4 months) and old (18 or 26 months) rats. In addition, we used electron microscopic immunogold procedures to locate and measure the amount of the enzyme in the mitochondrial matrix.
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9

Yang, Xiaoyan, Jing Shi, Haihong Lei, Bin Xia, and Dezhi Mu. "Neonatal-onset carbamoyl phosphate synthetase I deficiency." Medicine 96, no. 26 (2017): e7365. http://dx.doi.org/10.1097/md.0000000000007365.

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10

Ahuja, Anupama, Cristina Purcarea, Hedeel I. Guy, and David R. Evans. "A Novel Carbamoyl-Phosphate Synthetase fromAquifex aeolicus." Journal of Biological Chemistry 276, no. 49 (2001): 45694–703. http://dx.doi.org/10.1074/jbc.m106382200.

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11

Holden, Hazel M., James B. Thoden, and Frank M. Raushel. "Carbamoyl phosphate synthetase: a tunnel runs through it." Current Opinion in Structural Biology 8, no. 6 (1998): 679–85. http://dx.doi.org/10.1016/s0959-440x(98)80086-9.

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12

Kasahara, M., and M. Obmori. "Carbamoyl Phosphate Synthetase of the Cyanobacterium Anabaena cylindrica." Plant and Cell Physiology 38, no. 6 (1997): 734–39. http://dx.doi.org/10.1093/oxfordjournals.pcp.a029227.

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13

Graves, Lee M., Hedeel I. Guy, Piotr Kozlowski, et al. "Regulation of carbamoyl phosphate synthetase by MAP kinase." Nature 403, no. 6767 (2000): 328–32. http://dx.doi.org/10.1038/35002111.

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14

Thoden, James B., Xinyi Huang, Jungwook Kim, Frank M. Raushel, and Hazel M. Holden. "Long-range allosteric transitions in carbamoyl phosphate synthetase." Protein Science 13, no. 9 (2004): 2398–405. http://dx.doi.org/10.1110/ps.04822704.

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15

Javid-Majd, Farah, Leisha S. Mullins, Frank M. Raushel, and Michelle A. Stapleton. "The Differentially Conserved Residues of Carbamoyl-Phosphate Synthetase." Journal of Biological Chemistry 275, no. 7 (2000): 5073–80. http://dx.doi.org/10.1074/jbc.275.7.5073.

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16

Guy, Hedeel I., Bernard Schmidt, Guy Hervé, and David R. Evans. "Pressure-induced Dissociation of Carbamoyl-Phosphate Synthetase Domains." Journal of Biological Chemistry 273, no. 23 (1998): 14172–78. http://dx.doi.org/10.1074/jbc.273.23.14172.

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17

Kothe, Michael, Cristina Purcarea, Hedeel I. Guy, David R. Evans, and Susan G. Powers-Lee. "Direct demonstration of carbamoyl phosphate formation on the C-terminal domain of carbamoyl phosphate synthetase." Protein Science 14, no. 1 (2009): 37–44. http://dx.doi.org/10.1110/ps.041041305.

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18

Cohen, N. S., F. S. Kyan, S. S. Kyan, C. W. Cheung, and L. Raijman. "The apparent Km of ammonia for carbamoyl phosphate synthetase (ammonia) in situ." Biochemical Journal 229, no. 1 (1985): 205–11. http://dx.doi.org/10.1042/bj2290205.

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Experiments with carbamoyl phosphate synthetase (ammonia) in solution and in isolated mitochondria are reported which show the following. NH3 rather than NH4+ is the substrate of the enzyme. The apparent Km of NH3 for the purified enzyme is about 38 microM. The apparent Km for NH3 measured in intact isolated mitochondria is about 13 microM. This value was obtained for both coupled and uncoupled mitochondria and was unchanged when the rate of carbamoyl phosphate synthesis was increased 2-fold by incubating uncoupled mitochondria in the presence of 5 mM-N-acetylglutamate. According to the litera
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19

Gaasbeek Janzen, J. W., A. F. Moorman, W. H. Lamers, and R. Charles. "Development of the heterogeneous distribution of carbamoyl-phosphate synthetase (ammonia) in rat-liver parenchyma during postnatal development." Journal of Histochemistry & Cytochemistry 33, no. 12 (1985): 1205–11. http://dx.doi.org/10.1177/33.12.4067274.

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Carbamoyl-phosphate synthetase (ammonia) is homogeneously distributed in rat-liver parenchyma at birth, as demonstrated by immunohistochemistry. A heterogeneous distribution can first be demonstrated at 6 days post partum, but can be masked by use of a too sensitive detection system. This heterogeneity is established by a decrease in enzyme content around the hepatic venules and a considerable increase in enzyme content in the remaining parenchyma. The perivenous decrease in enzyme content does not occur in all hepatocytes synchronously. The adult type of heterogeneity is characterized by a pe
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20

Hewagama, Anura, Hedeel I. Guy, John F. Vickrey, and David R. Evans. "Functional Linkage between the Glutaminase and Synthetase Domains of Carbamoyl-phosphate Synthetase." Journal of Biological Chemistry 274, no. 40 (1999): 28240–45. http://dx.doi.org/10.1074/jbc.274.40.28240.

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21

Smith, D. D., and J. W. Campbell. "Distribution of glutamine synthetase and carbamoyl-phosphate synthetase I in vertebrate liver." Proceedings of the National Academy of Sciences 85, no. 1 (1988): 160–64. http://dx.doi.org/10.1073/pnas.85.1.160.

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22

Guillou, F., S. D. Rubino, R. S. Markovitz, D. M. Kinney, and C. J. Lusty. "Escherichia coli carbamoyl-phosphate synthetase: domains of glutaminase and synthetase subunit interaction." Proceedings of the National Academy of Sciences 86, no. 21 (1989): 8304–8. http://dx.doi.org/10.1073/pnas.86.21.8304.

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23

Cohen, N. S., C. W. Cheung, and L. Raijman. "Altered enzyme activities and citrulline synthesis in liver mitochondria from ornithine carbamoyltransferase-deficient sparse-furash mice." Biochemical Journal 257, no. 1 (1989): 251–57. http://dx.doi.org/10.1042/bj2570251.

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Male mice carrying the spfash mutation have 5-10% of the normal activity of ornithine carbamoyltransferase, yet are only slightly hyperammonaemic and develop quite well. A study of liver mitochondria from normal and spfash males showed that they differ in important ways. (1) The spfash liver contains about 33% more mitochondrial protein per g than does normal liver. (2) The specific activities of carbamoyl-phosphate synthetase (ammonia) and glutamate dehydrogenase are about 15% lower than normal in mitochondria from spfash mice, whereas those of beta-hydroxybutyrate dehydrogenase and cytochrom
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24

Powers-Lee, S. G., and K. Corina. "Domain structure of rat liver carbamoyl phosphate synthetase I." Journal of Biological Chemistry 261, no. 33 (1986): 15349–52. http://dx.doi.org/10.1016/s0021-9258(18)66714-6.

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25

Sahay, Nisha, Hedeel I. Guy, Xin Liu, and David R. Evans. "Regulation of anEscherichia coli/Mammalian Chimeric Carbamoyl-phosphate Synthetase." Journal of Biological Chemistry 273, no. 47 (1998): 31195–202. http://dx.doi.org/10.1074/jbc.273.47.31195.

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26

Kim, Jungwook, and Frank M. Raushel. "Access to the carbamate tunnel of carbamoyl phosphate synthetase." Archives of Biochemistry and Biophysics 425, no. 1 (2004): 33–41. http://dx.doi.org/10.1016/j.abb.2004.02.031.

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27

Marrero, Mario, Russell A. Prough, Robert S. Putnam, Michael Bennett, and Leon Milewich. "Inhibition of carbamoyl phosphate synthetase-I by dietary dehydroepiandrosterone." Journal of Steroid Biochemistry and Molecular Biology 38, no. 5 (1991): 599–609. http://dx.doi.org/10.1016/0960-0760(91)90319-z.

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28

Alcántara, Cristina, Javier Cervera, and Vicente Rubio. "Carbamate kinase can replace in vivo carbamoyl phosphate synthetase. Implications for the evolution of carbamoyl phosphate biosynthesis." FEBS Letters 484, no. 3 (2000): 261–64. http://dx.doi.org/10.1016/s0014-5793(00)02168-2.

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29

Nicoloff, Hervé, Jean-Claude Hubert, and Françoise Bringel. "In Lactobacillus plantarum, Carbamoyl Phosphate Is Synthesized by Two Carbamoyl-Phosphate Synthetases (CPS): Carbon Dioxide Differentiates the Arginine-Repressed from the Pyrimidine-Regulated CPS." Journal of Bacteriology 182, no. 12 (2000): 3416–22. http://dx.doi.org/10.1128/jb.182.12.3416-3422.2000.

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ABSTRACT Carbamoyl phosphate (CP) is an intermediate in pyrimidine and arginine biosynthesis. Carbamoyl-phosphate synthetase (CPS) contains a small amidotransferase subunit (GLN) that hydrolyzes glutamine and transfers ammonia to the large synthetase subunit (SYN), where CP biosynthesis occurs in the presence of ATP and CO2.Lactobacillus plantarum, a lactic acid bacterium, harbors a pyrimidine-inhibited CPS (CPS-P; Elagöz et al., Gene 182:37–43, 1996) and an arginine-repressed CPS (CPS-A). Sequencing has shown that CPS-A is encoded by carA (GLN) and carB (SYN). Transcriptional studies have de
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30

Thoden, James B., Sophie G. Miran, James C. Phillips, Andrew J. Howard, Frank M. Raushel, and Hazel M. Holden. "Carbamoyl Phosphate Synthetase: Caught in the Act of Glutamine Hydrolysis†,‡." Biochemistry 37, no. 25 (1998): 8825–31. http://dx.doi.org/10.1021/bi9807761.

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31

Miles, Bryant W., Jennifer A. Banzon, and Frank M. Raushel. "Regulatory Control of the Amidotransferase Domain of Carbamoyl Phosphate Synthetase†." Biochemistry 37, no. 47 (1998): 16773–79. http://dx.doi.org/10.1021/bi982018g.

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32

Raushel, Frank M., James B. Thoden, Gregory D. Reinhart, and Hazel M. Holden. "Carbamoyl phosphate synthetase: a crooked path from substrates to products." Current Opinion in Chemical Biology 2, no. 5 (1998): 624–32. http://dx.doi.org/10.1016/s1367-5931(98)80094-x.

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33

Miles, Bryant W., and Frank M. Raushel. "Synchronization of the Three Reaction Centers within Carbamoyl Phosphate Synthetase†." Biochemistry 39, no. 17 (2000): 5051–56. http://dx.doi.org/10.1021/bi992772h.

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34

Braxton, B. L., Leisha S. Mullins, Frank M. Raushel, and Gregory D. Reinhart. "Allosteric Effects of Carbamoyl Phosphate Synthetase fromEscherichia coliAre Entropy-Driven†." Biochemistry 35, no. 36 (1996): 11918–24. http://dx.doi.org/10.1021/bi961305m.

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35

Kasahara, Mureo, Seisuke Sakamoto, Takanobu Shigeta, et al. "Living-donor liver transplantation for carbamoyl phosphate synthetase 1 deficiency." Pediatric Transplantation 14, no. 8 (2010): 1036–40. http://dx.doi.org/10.1111/j.1399-3046.2010.01402.x.

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36

Nunley, S., and D. Ghosh. "Teaching NeuroImages: MRI findings in carbamoyl phosphate synthetase 1 deficiency." Neurology 84, no. 18 (2015): e138-e139. http://dx.doi.org/10.1212/wnl.0000000000001546.

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37

Kim, Jungwook, Stanley Howell, Xinyi Huang, and Frank M. Raushel. "Structural Defects within the Carbamate Tunnel of Carbamoyl Phosphate Synthetase†." Biochemistry 41, no. 42 (2002): 12575–81. http://dx.doi.org/10.1021/bi020421o.

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38

Huang, Min, Piotr Kozlowski, Matthew Collins, Yanhong Wang, Timothy A. Haystead, and Lee M. Graves. "Caspase-Dependent Cleavage of Carbamoyl Phosphate Synthetase II during Apoptosis." Molecular Pharmacology 61, no. 3 (2002): 569–77. http://dx.doi.org/10.1124/mol.61.3.569.

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39

Summar, Marshall L., James V. Gainer, Mias Pretorius, et al. "Relationship Between Carbamoyl-Phosphate Synthetase Genotype and Systemic Vascular Function." Hypertension 43, no. 2 (2004): 186–91. http://dx.doi.org/10.1161/01.hyp.0000112424.06921.52.

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40

Zhang, Guoqing, Yulin Chen, Huiqun Ju, et al. "Carbamoyl phosphate synthetase 1 deficiency diagnosed by whole exome sequencing." Journal of Clinical Laboratory Analysis 32, no. 2 (2017): e22241. http://dx.doi.org/10.1002/jcla.22241.

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41

Flores, Maria Vega C., and Thomas S. Stewart. "Plasmodium falciparum: A Microassay for the Malarial Carbamoyl Phosphate Synthetase." Experimental Parasitology 88, no. 3 (1998): 243–45. http://dx.doi.org/10.1006/expr.1998.4240.

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42

Kothe, M. "Nucleotide recognition in the ATP-grasp protein carbamoyl phosphate synthetase." Protein Science 13, no. 2 (2004): 466–75. http://dx.doi.org/10.1110/ps.03416804.

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43

Cardona, Diana M., Xiaokui Zhang, and Chen Liu. "Loss of Carbamoyl Phosphate Synthetase I in Small-Intestinal Adenocarcinoma." American Journal of Clinical Pathology 132, no. 6 (2009): 877–82. http://dx.doi.org/10.1309/ajcp74xgrfwtflju.

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44

Flores, Maria Vega C., William J. O'Sullivan, and Thomas S. Stewart. "Characterisation of the carbamoyl phosphate synthetase gene from Plasmodium falciparum." Molecular and Biochemical Parasitology 68, no. 2 (1994): 315–18. http://dx.doi.org/10.1016/0166-6851(94)90176-7.

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45

Stapleton, Michelle A., Farah Javid-Majd, Marilyn F. Harmon, et al. "Role of Conserved Residues within the Carboxy Phosphate Domain of Carbamoyl Phosphate Synthetase†." Biochemistry 35, no. 45 (1996): 14352–61. http://dx.doi.org/10.1021/bi961183y.

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46

Krátký, Martin, Eva Novotná, Shalini Saxena, et al. "Salicylanilide Diethyl Phosphates as Potential Inhibitors of Some Mycobacterial Enzymes." Scientific World Journal 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/703053.

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Antimycobacterially active salicylanilide diethyl phosphates were evaluated to identify their potential drug target(s) for the inhibition of several mycobacterial enzymes, including isocitrate lyase, L-alanine dehydrogenase (MtAlaDH), lysineε-aminotransferase, chorismate mutase, and pantothenate synthetase. The enzymes are related to the nongrowing state ofMycobacterium tuberculosis. Salicylanilide diethyl phosphates represent new candidates with significant inhibitory activity especially against L-alanine dehydrogenase. The most activeMtAlaDH inhibitor, 5-chloro-2-[(3-chlorophenyl)carbamoyl]p
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47

Elgar, Greg, and J. Paul Schofield. "Carbamoyl phosphate synthetase (CPSase) in the PYR1-3 multigene ofDictyostelium discoideum." DNA Sequence 2, no. 4 (1992): 219–26. http://dx.doi.org/10.3109/10425179209020806.

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48

Wong, Lee-Jun C. "Postpartum Coma and Death due to Carbamoyl-Phosphate Synthetase I Deficiency." Annals of Internal Medicine 120, no. 3 (1994): 216. http://dx.doi.org/10.7326/0003-4819-120-3-199402010-00007.

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49

Madan, A. "Carbamoyl Phosphate Synthetase Polymorphisms as a Risk Factor for Necrotizing Enterocolitis." Yearbook of Neonatal and Perinatal Medicine 2008 (January 2008): 220–21. http://dx.doi.org/10.1016/s8756-5005(08)79165-0.

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50

Martínez, Ana Isabel, Isabel Pérez-Arellano, Satu Pekkala, Belén Barcelona, and Javier Cervera. "Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency." Molecular Genetics and Metabolism 101, no. 4 (2010): 311–23. http://dx.doi.org/10.1016/j.ymgme.2010.08.002.

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