Dissertations / Theses: 'Decarboxylases'

1

Fogle, Emily Joyce. "Kinetic characterization of pyridoxal 5'-phosphate dependent decarboxylases : dialkylglycine decarboxylase and diaminopimelate decarboxylase /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2005. http://uclibs.org/PID/11984.

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2

Spence, Michael Patrick. "Plant aromatic amino acid decarboxylases: Evolutionary divergence, physiological function, structure function relationships and biochemical properties." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/49432.

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Plant aromatic amino acid decarboxylases (AAADs) are a group of economically important enzymes categorically joined through their pyridoxal 5'-phosphate (PLP) dependence and sequence homology. Extensive evolutionary divergence of this enzyme family has resulted in a selection of enzymes with stringent aromatic amino acid substrate specificities. Variations in substrate specificities enable individual enzymes to catalyze key reactions in a diverse set of pathways impacting the synthesis of monoterpenoid indole alkaloids (including the pharmacologically active vinblastine and quinine), benzylisoquinoline alkaloids (including the pharmacologically active papaverine, codeine, morphine, and sanguinarine), and antioxidant and chemotherapeutic amides. Recent studies of plant AAAD proteins demonstrated that in addition to the typical decarboxylation enzymes, some annotated plant AAAD proteins are actually aromatic acetaldehyde synthases (AASs). These AASs catalyze a decarboxylation-oxidative deamination process of aromatic amino acids, leading to the production of aromatic acetaldehydes rather than the AAAD derived arylalkylamines. Research has implicated that plant AAS enzymes are involved in the production of volatile flower scents, floral attractants, and defensive phenolic acetaldehyde secondary metabolites. Historically, the structural elements responsible for differentiating plant AAAD substrate specificity and activity have been difficult to identify due to strong AAAD and AAS inter-enzyme homology. Through extensive bioinformatic analysis and experimental verification of plant AAADs, we have determined some structural elements unique to given types of AAADs. This document highlights structural components apparently responsible for the differentiation of activity and substrate specificity. In addition to producing primary sequence identifiers capable of AAAD activity and substrate specificity differentiation, this work has also demonstrated applications of AAAD enzyme engineering and novel activity identification.
Ph. D.

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3

Parsanejad, Reza. "Phosphoenolpyruvate carboxykinase and ornithine decarboxylase genes : allelic variations and associations with traits in poultry." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84307.

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The objectives of this study were to identify genetic variants, develop the respective haplotypes (combination of alleles) and investigate the association of identified variants with economically important traits in two candidate genes. The first gene was Phosphoenolpyruvate carboxykinase (PEPCK) which is a key regulatory enzyme of gluconeogenesis. The second candidate gene, Ornithine decarboxylase (ODC), is a rate-limiting enzyme in polyamine biosynthesis. It has a significant role in DNA synthesis and cell proliferation. We first analyzed the genetic variability of PEPCK-C, the gene which codes for the cytosolic form of PEPCK. A 3792 by segment of 5'-region of the PEPCK-C gene (pos. -1723 to 2069) was sequenced in 32 White Leghorn chickens (a total of 64 genomes). A total of 19 single nucleotide polymorphisms (SNPs) were identified. We then analyzed the genetic variability of ODC. A 5 kb sequence of 3' end of the gene was sequenced in 20 White Leghorn chickens (a total of 40 genomes). A total of 63 variant sites were identified. The rate of insertion/deletion in ODC was 16%, whereas neither deletions nor insertions were present in PEPCK-C. Gene trees were constructed for both genes assuming maximal parsimony. This led to the delineation of 6 haplotypes in PEPCK-C. Two of the SNPs coincided with RFLP detectable by the restriction enzymes AciI and BstEII, respectively. Three haplotypes in ODC were defined. In the next step, White Leghorn chickens from a non-selected closed population were typed for these two PEPCK-C RFLP. The two RFLP gave rise to three alleles (or haplotype classes), which in turn defined six genotypes. A comparison of genotypes revealed significant differences in feed efficiency (FE) and residual feed consumption (RFC). There was significant interaction between PEPCK-C genotypes and mitochondrial PEPCK (PEPCK-M) genotypes defined by an RFLP. The latter enzyme catalyzes the same reaction, but is located in the matrix of t

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4

Blalock, LeeAnn Talarico. "Expression of pyruvate decarboxylase in a Gram positive host Sarcina ventriculi pyruvate decarboxylase versus other known pyruvate decarboxylases /." [Gainesville, Fla.] : University of Florida, 2003. http://purl.fcla.edu/fcla/etd/UFE0002366.

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5

Tran, Linh N. "Synthesizing Antifungal Agents." Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/TranLN2007.pdf.

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6

Pandey, Arti Sharma. "Structure based mechanistic studies on 2-ketopropyl coenzyme M oxidoreductase / carboxylase from Xanthobacter autotrophicus and [FeFe] hydrogenase from Clostridium pasteurianum." Diss., Montana State University, 2007. http://etd.lib.montana.edu/etd/2007/pandey/PandeyA1207.pdf.

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7

丘國明 and Kwok-ming Yao. "Purification and characterization of ornithine decarbozylase fromtetrahymena thermophila." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1986. http://hub.hku.hk/bib/B31207480.

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Yao, Kwok-ming. "Purification and characterization of ornithine decarbozylase fromtetrahymena thermophila /." Hong Kong : [University of Hong Kong], 1986. http://sunzi.lib.hku.hk/hkuto/record.jsp?B12322829.

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9

Laitinen, Päivi. "Antizyme in the regulation of mouse brain ornithine decarboxylase." Oulu : University of Oulu, 1986. http://catalog.hathitrust.org/api/volumes/oclc/16882622.html.

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10

GLASS, JAMES RUSSELL. "POLYAMINE-MEDIATED DEGRADATION OF ORNITHINE DECARBOXYLASE IN CHINESE HAMSTER OVARY CELLS." Diss., The University of Arizona, 1987. http://hdl.handle.net/10150/184002.

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The objective of this research was to identify specific mechanisms involved in the regulation of ornithine decarboxylase, the first enzyme in the polyamine biosynthetic pathway. Immunochemical techniques were used to study post-translational modifications of the ODC protein in relation to activity alterations. Initial experimentation showed that Chinese hamster cells maintained in a defined medium express an ODC protein stable to intracellular degradation. Treatment of these cells with exogenous ornithine or polyamines resulted in a rapid loss of enzyme activity, without detectable changes in the enzyme specific activity. The loss of enzyme activity was a result of accelerated ODC degradation, as determined by immunoprecipitation of pre-labeled protein. In addition, spermidine, but not ornithine, totally inhibited new ODC synthesis. The mechanism of accelerated ODC degradation was investigated and found to occur by an apparent novel mechanism. Degradation of ODC was both ubiquitin-independent and non-lysosomal, and there was also no detectable accumulation of a modified form of ODC protein. In addition, it was found that a component of protein synthesis is required for this process, as inhibitors (cycloheximide, emetine, puromycin) blocked polyamine-accelerated degradation. ODC cDNA was used to synthesize both ODC specific mRNA and protein using in vitro synthesis. These systems may allow the generation of sufficient quantities of material which can be used to recreate in vitro the specific components involved in polyamine inhibition of ODC synthesis and the protease(s) responsible for degradation. The major finding of this work is the direct demonstration that ODC is a stable intracellular protein in the absence of putrescine and spermidine depleted cells (Chapter 2). In addition, that degradation occurs by a novel mechanism, with a requirement for some component of protein synthesis (Chapter 3). Finally, these studies describe the in vitro production of ODC protein and mRNA, which should facilitate further studies of polyamine regulation of ODC degradation and synthesis (Chapter 4).

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11

Liang, Jing. "Biochemical Studies of Aromatic Amino Acid Decarboxylases and Acetaldehyde Synthases." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/96242.

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Pyridoxal 5'-phosphate (PLP)-dependent enzymes widely exist in most living organisms from bacteria to human. Among different types of PLP-dependent enzymes, aromatic amino acid decarboxylases play critical physiological roles because many aromatic amines are essential neurotransmitters. This dissertation concerns the biochemical characterization of several PLP-dependent decarboxylases and aims to understand the structure-function relationships, especially critical residues involved in their catalysis. We first present an overview of the current opinions and recent advances in structure-function relationships of several PLP-dependent enzymes with the first reaction step at substrate Cα position, including decarboxylase and acetaldehyde synthase. L-3, 4-dihydroxyphenylalanine (L-dopa) decarboxylase (DDC) is a model enzyme we use as a reference because the structures and functions of DDC are relatively well established. We previously identified two annotated DDC-like proteins from Drosophila indeed catalyzing a decarboxylation-oxidative deamination reaction of L-dopa to form 3,4-dihydroxyphenylacetaldehyde (DHPA), CO2, NH3, and H2O2 and we named these proteins as DHPA synthases due to the physiological importance of DHPA for cuticle protein crosslinking. Our results provide an efficient way to identify more DHPA synthase enzymes from DDC based on sequence identity and the signature residues we identified (Asn192 in DHPA synthase versus His192 in DDC), and we also propose a reasonable explanation of the mechanism. The results that H2O2 produced by the reaction can be reused in the reaction as an oxidizing agent suggest a way to avoid the oxidative stress of H2O2. We then compared tyrosine decarboxylase (TyDC) with DDC. As the enzyme catalyzing the first step of insect neurotransmitter tyramine/octopamine synthesis, the biochemical characteristics of insect TyDC have not been thoroughly elucidated yet because of the expression difficulty. We expressed one insect TyDC and analyzed its biochemical properties. Our enzyme analyses reveal that insect TyDC prefers tyrosine as a substrate, but it also displays some activity to L-dopa. Spectral analysis also shows that the absorbance spectra of insect TyDC have major differences as compared to those of DDC. Site-directed mutagenesis indicates that the interactions between residue Asn304 with PLP is primarily responsible for its spectra differences of TyDC as compared to those of DDC and also is involved in higher substrate affinity to L-tyrosine. Another active site residue (Ser353) has the main effect on substrate selectivity. Our results show the biochemical properties of TyDC for the first time and also provide some insights into the mechanism of its substrate selectivity.
PHD

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12

Phillips, Susan R. "Spectroscopic investigation of tryptophan microenvironments in bovine lens proteins." Diss., Georgia Institute of Technology, 1986. http://hdl.handle.net/1853/32973.

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13

羅志良 and Che-leung Law. "Induction of ornithine decarboxylase activity in reuber H-35 hepatoma cells by systems A and N amino acids and the possible involvement ofthe Na+/H+ antiporter." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1986. http://hub.hku.hk/bib/B31207315.

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14

Law, Che-leung. "Induction of ornithine decarboxylase activity in reuber H-35 hepatoma cells by systems A and N amino acids and the possible involvement of the Na+/H+ antiporter /." [Hong Kong : University of Hong Kong], 1986. http://sunzi.lib.hku.hk/hkuto/record.jsp?B12323986.

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15

Rossoni, Luca. "Towards the bioproduction of methacrylic acid : a case study on the use of decarboxylases." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/34387/.

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In this study, the biocatalytic production of methacrylic acid (MAA), a commodity chemical with a large global market, was investigated. The target was to develop MAA formation via enzymatic decarboxylation of itaconic, mesaconic, citraconic and citramalic acid. Several candidate enzymes were tested, but none catalysed the target reactions. Therefore, a novel high throughput screening method for decarboxylases was developed to enable protein engineering. The screening assay detected gaseous CO2 with a pH-dependent colorimetric reaction, in a 96-well format. Focused mutagenesis was then performed on the mevalonate diphosphate decarboxylases (MVD) from Saccharomyces cerevisiae and from Picrophilus torridus. However, MAA formation was not observed, even after screening over 3800 variants. Further investigation was then performed on some of the candidates to understand why MAA was not formed and to develop alternative strategies for enzyme selection. P. torridus MVD was discovered to belong to a new class of enzymes, mevalonate-3-kinase, and to be part of a novel archaeal mevalonate pathway. The enzyme also catalysed the formation of isobutene from 3-hydroxyisovalerate with unprecedented production rates. S. cerevisiae and Aspergillus niger phenylacrylic acid decarboxylases, previously believed to be cofactor-free enzymes, were proposed to require divalent metals and a novel organic cofactor. The enzymatic mechanism of Pseudomonas fluorescens α-amino-β-carboxymuconate-ε-semialdehyde (ACMS) decarboxylase was investigated. Through inhibition studies, it was demonstrated that the aldehyde and amino moieties of ACMS could be directly involved in catalysis, in contrast to the previously reported mechanism. This information partially explains why some of these candidates could not catalyse the target reaction, and provides insights into their potential future use for the bioproduction of MAA. Although this route does not seem feasible at present, this study gives foundation and guidance for future investigations.

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16

Dassanayake, Ranil Samantha. "Genotyping Candida species and molecular analysis of C. albicans gene encoding mevalonate pyrophosphate decarboxylase." Thesis, Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23249791.

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17

Versaux-Botteri, Claudine. "Expression des decarboxylases du glutamate (gad 65 et 67) durant la retinogenese chez le rat albinos." Paris 6, 1995. http://www.theses.fr/1995PA066230.

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Des etudes immunohistochimiques, par hybridation in situ et par reaction de polymerisation en chaine revelent une apparition differentielle des deux enzymes de synthese du gaba, les decarboxylases du glutamate (gad) 65 et 67 durant la maturation postnatale de la retine chez le rat. La gad 65 apparait dans les couches nucleaire et plexiforme internes lorsque debute la synaptogenese, c'est-a-dire, vers le 5/6#e#m#e jour postnatal. Par contre, la gad 67 est observee des la naissance, avant l'etablissement des synapses. Par ailleurs, la gad 67 synthetise le gaba exprime transitoirement dans les cellules horizontales. Du 5#e#m#e au 15#e#m#e jour postnatal. L'expression decalee des deux gad suggere une fonction differente pour le gaba synthetise par l'une ou l'autre des enzymes: le gaba synthetise par la gad 67 possederait une action neurotrophique alors le gaba synthetise par la gad 65 serait implique dans la neurotransmission. De plus, nous avons montre la presence transitoire dans les premiers jours apres la naissance d'un transcrit de l'arnm de la gad 67 contenant un exon supplementaire attestant de l'importance de la 1#e#r#e semaine postnatale pour la mise en place du systeme gabaergique retinien. Chez l'adulte, la dualite fonctionnelle possible du gaba souleve la question de sa fonction lorsqu'il est colocalise avec d'autres neurotransmetteurs, en particulier avec la dopamine

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18

RONDET, SABINE. "Biosynthese des sterols : 4-carboxy-sterol decarboxylases de plante superieure et de levure ; identification, caracterisation et purification." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13225.

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La voie de biosynthese des sterols comporte deux etapes de demethylation en c4. Le systeme multienzymatique catalysant ce processus comprend au moins trois enzymes distinctes : la 4-methylsterol oxydase (4mo), la 4-carboxysterol decarboxylase (4cd) et la 3-ceto steroide oxydoreductase (3 cor). Nous avons pu, pour la premiere fois, identifier la 4cd de plante superieure et de levure dans des microsomes de zea mays et de saccharomyces cerevisiae, apres synthese de differents substrats et identification rigoureuse du produit de reaction, a savoir un 3-cetosteroide decarboxyle. Nous avons ensuite mis au point un test enzymatique operationnel et fiable, ce qui nous a permis d'etablir les parametres enzymologiques de la reaction. Les resultats indiquent notamment que l'etape de decarboxylation n'est pas limitante dans le processus global de demethylation des sterols en c4. Le mode d'action de la 4cd s'apparente a celui d'une 3-hydroxysterol deshydrogenase dependante de nad(p) -, nad + etant beaucoup plus efficace que nadp +. De plus, nous avons montre que la reaction catalysee par la 4cd est independante de l'oxygene moleculaire, ce qui indique l'existence de deux phases distinctes dans le processus de demethylation en c4, a savoir : une phase strictement dependante de l'oxygene catalysee par la 4mo, suivie d'une phase independante de l'oxygene, catalysee par la 4cd et la 3cor. La recherche d'inhibiteurs du systeme de demethylation en c4 nous a conduits a l'obtention de deux inhibiteurs efficaces de la 4mo et de la 4cd de mais respectivement. Nous avons entrepris la purification de la 4cd de mais et nous avons obtenu apres trois etapes de chromatographie (echange d'anions, affinite puis exclusion) un taux de purification de 300 a 500 fois, ce qui permet d'envisager le microsequencage de la proteine ou la production d'anticorps specifiques, dans l'optique du clonage du gene correspondant.

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19

Chintapakorn, Yupynn 1960. "An antisense approach to study the roles of arginine decarboxylase and putrescine N-methyltransferase in alkaloid metabolism in Nicotiana tabacum L." Monash University, Dept. of Biological Sciences, 2002. http://arrow.monash.edu.au/hdl/1959.1/7622.

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20

Santibanez, Rodrigo. "The effect of high hydrostatic pressure on histidine decarboxylase and histamine forming bacteria /." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101172.

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Increasing consumer demand for fresh fishery products with minimized loss of their nutritional properties is forcing food industry to look for alternative technologies to maintain the fresh attributes, stability and safety of foods. Demand for fresh tuna fish is no exception, being a valuable source of nutrients with immense health benefits. However, this product is highly perishable and has been commonly implicated in scombroid (histamine) poisoning caused by microbial decarboxylation of histidine contained in high levels in the tissues of scombroid fishes. Current techniques are inadequate for the prevention of histamine formation in fresh fishery products and high pressure processing is a potential alternative for it can inactivate microorganisms and enzymes, without affecting (or only minimally altering) the quality characteristics of foodstuffs. Previous studies have shown a decrease in histamine formation after a high pressure treatment and this study focuses on the effect of high pressure on the histidine decarboxylase enzyme and selected histamine forming microorganisms involved in histamine formation.
Commercial histidine decarboxylase suspended in different media (buffer solution and fish slurry with and without added histidine) was submitted to different high pressure treatments (200--400 MPa) with distinct time durations (0--60 min) at room temperature (20°C--25°C). Enzymatic activity of pressure treated and control samples were then compared by measuring histamine formation. Results were similar in all media; a 200 MPa treatment increased the enzymatic activity a little more than 20% as time increased; a 300 MPa treatment increased activity over 20% at first, followed by a decrease in activity as time increased only to reach a level of residual activity similar or only slightly lower than control samples; and a 400 MPa treatment reduced enzyme activity as time increased to a level of 55% residual activity in a buffer solution where the greatest inactivation was observed.
Enzyme activation and inactivation were affected by a dual effect attributed to a pulse effect, which caused a shift in activity and was independent of the length of the treatment, and a pressure-hold effect, during which activation or inactivation followed first order kinetics. The enzyme appeared highly resistant to pressure in all media as observed from D-values (>2700 min) and pressure sensitivity of destruction rate (zp) values (>500 MPa).
Inactivation of non-pathogen histamine forming bacteria (HFB) Escherichia coli K12 and Bacillus megaterium was evaluated by inoculating cultures in a fish tissue homogenate. Surviving colonies were enumerated after the treatments observing inactivation described by the same dual effect described earlier. Pressures above 300 MPa achieved a significant destruction of E. coli K12 (> 4 log-cycles) while B. megaterium appeared highly resistant for only a 2 log-cycle reduction was observed after at the highest pressure treatment conditions (400 MPa, 20 min).
D-values for both microorganisms decreased as pressure increased being significantly smaller for E. coli K 12, which also appeared to be more sensitive to pressure changes as observed from the zp values (zp = 151.51 MPa and zp = 909.10 MPa for E. coli and B. megaterium respectively. Inactivation caused by the pulse effect appeared very effective for both microorganisms as pressure increased, particularly at 400 MPa (PE > 1.25).

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21

Sutiono, Samuel [Verfasser], Volker [Akademischer Betreuer] Sieber, Volker [Gutachter] Sieber, Sonja-Verena [Gutachter] Albers, and Bastian [Gutachter] Blombach. "Development of decarboxylases and dehydratases as valuable biocatalysts for the production of fine chemicals / Samuel Sutiono ; Gutachter: Volker Sieber, Sonja-Verena Albers, Bastian Blombach ; Betreuer: Volker Sieber." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1227580525/34.

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22

Aljabri, Hareb Mohammed. "Comparative analysis of Anopheles gambiae L-tyrosine decarboxylase and L-DOPA decarboxylase." Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/34788.

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A major pathway of tyramine and dopamine synthesis in insects is through the decarboxylation of tyrosine and DOPA, respectively. Although tyrosine decarboxylase (TDC) has been mentioned in some reports, it has never been critically analyzed. The high sequence identity shared by tyrosine decarboxylase and DOPA decarboxylase in insects, and the similar structures of the substrates, tyrosine and DOPA, raise the possibility that both tyrosine decarboxylase and DOPA decarboxylase (DDC) have activities to tyrosine and DOPA. In this study, after tyrosine decarboxylase and DOPA decarboxylase enzymes of Anopheles gambiae were expressed, their substrate specificities and biochemical properties were critically analyzed. My results provide clear biochemical evidence establishing that the mosquito tyrosine decarboxylase functions primarily on the production of tyramine with low activity to DOPA. In contrast, mosquito DOPA decarboxylase is highly specific to DOPA with essentially no activity to tyrosine.
Master of Science in Life Sciences

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23

Orlow, Melanie von. "Phosphatidylserin-Decarboxylase in Pflanzen." [S.l. : s.n.], 2003. http://www.diss.fu-berlin.de/2003/254/index.html.

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24

Grant, P. L. "The mechanism of glutamate decarboxylase." Thesis, Bucks New University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376413.

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Marlow, Victoria A. "Mechanistic studies of acetolactate decarboxylase." Thesis, University of Warwick, 2013. http://wrap.warwick.ac.uk/58624/.

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Acetolactate decarboxylase (ALDC) is a bacterial enzyme of the butanediol fermentation pathway that decarboxylates (S)-acetolactate into (R)-acetoin. Remarkably this enzyme also catalyses the decarboxylation of the opposite enantiomer, (R)-acetolactate, to give the same product, (R)-acetoin. It is unusual for an enzyme to convert racemic substrate into an enantiomerically pure product. This unusual stereochemical control has led to extensive study of the ALDC mechanism and the hypothesis that ALDC catalyses the rearrangement of (R)-acetolactate into (S)-acetolactate prior to decarboxylation. The research presented in this thesis sought to gain insight into the molecular mechanism of the ALDC catalysed reaction by using a combination of kinetic and structural techniques. Bacillus subtilis alsD encoding ALDC was cloned into an expression vector and a series of active site mutants were prepared. The activity of mutant AlsD were determined using a circular dichroism based assay, which identified that the two active site glutamates and a basic residue are required for catalysis. A series of chiral transition state analogues were prepared in a two-step synthesis to give enantiomerically enriched 2,3-dihydroxy-2-methylbutanoic acid in reasonable yields. Three of the compounds were identified as competitive inhibitors, co-crystallised with Bacillus brevis ALDC and structures solved to 1.1-1.6 Å. These structures, coupled with inhibition studies and site-directed mutagenesis, provide an improved understanding of the molecular processes involved in the stereoselective decarboxylation of acetolactate. A mechanism for the transformation of each enantiomer of acetolactate is proposed.

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Reynolds, Jonathan James. "Structure-based drug discovery against a novel antimalarial drug target, S-adenosylmethionine decarboxylase/ornithine decarboxylase." Diss., University of Pretoria, 2012. http://hdl.handle.net/2263/27172.

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Malaria is one of the most life-threatening diseases affecting mankind, with over 3 billion people being at risk of infection, with most of these people living in Africa, South America and Asia. As the malaria parasite is rapidly becoming resistant to many of the possible treatments on the market, it is of upmost importance to identify new possible drug targets and describe drugs against these that are inexpensive, easy to manufacture and have a long shelf-life in order to combat malaria. One such target is the polyamine pathway. The polyamines putrescine, spermidine, and spermine are crucial for cell differentiation and proliferation. Interference with polyamine biosynthesis by inhibition of the rate-limiting enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) has been discussed as a potential chemotherapy of cancer and parasitic infections. Usually, both enzymes are individually transcribed and highly regulated as monofunctional proteins. However, ODC and AdoMetDC from P. falciparum (PfODC and PfAdoMetDC, respectively) are found as a unique bifunctional protein (PfAdoMetDC/ODC) in the malaria parasite, making it an enticing target for new, selective antimalarial chemotherapies. In order to apply structure-based drug discovery strategies to design inhibitors for PfAdoMetDC/ODC, the atomic resolution structures of these proteins are needed. Each individual domain has had its structure proposed through homology modelling; however atomic resolution structures of these domains are not yet available. The homology model of PfAdoMetDC/ODC has not yet been elucidated due to the interactions between the domains of the bifunctional protein not being fully understood. High levels of recombinant expression of the bifunctional protein have been either unsuccessful or resulted in the formation of insoluble proteins being produced. The purpose of this project is to optimise the recombinant expression of PfAdoMetDC/ODC, and the PfODC domain, to produce high yields of pure, soluble protein for subsequent atomic resolution structure determination. Ultimately, this will enable the utilisation of PfAdoMetDC/ODC in structure-based drug discovery strategies. Overexpression of P. falciparum proteins in E. coli is notoriously difficult, mainly due to the codon bias between the two species. Comparative studies were performed on four constructs of the PfAdoMetDC/ODC gene, containing either the wild-type, fully codon harmonised, or partially codon harmonised gene sequences to analyse the effect codon harmonisation had on protein expression and activity of both domains of PfAdoMetDC/ODC as well as on the monofunctional PfODC domain. Codon harmonisation did not improve the expression levels or the purity of recombinantly expressed PfAdoMetDC/ODC or the monofunctional PfODC domain. Truncated versions of both proteins, and contamination by the E. coli chaperone proteins DnaK and GroEL, were present in the protein samples even after purification by affinity chromatography. However, codon harmonisation improved the activity levels of the PfAdoMetDC domain, while decreasing the activity of the PfODC domain of PfAdoMetDC/ODC. Harmonisation of the monofunctional PfODC domain resulted in a decrease in the activity of the protein. In order to identify possible inhibitors of the PfODC domain of the bifunctional protein, a structure-based drug discovery study was initiated based on a homology model for PfODC. Four hundred compounds with known antimalarial activity were virtually screened against the PfODC homology model and the top two scoring compounds were selected for enzyme inhibition assays based on their predictive binding affinity against the enzyme, and two medium scoring compounds were selected as controls. Enzyme inhibition studies were performed on the bifunctional PfAdoMetDC/ODC to determine the effect the compounds had on both domains of the protein. Of the compounds assayed one of the compounds significantly reduced the activity levels of both domains of PfAdoMetDC/ODC. Additionally, one compound significantly reduced the activity level of the PfAdoMetDC domain of PfAdoMetDC/ODC. This work therefore contributes towards characterisation of the unique PfAdoMetDC/ODC in malaria parasites as a novel drug target.
Dissertation (MSc)--University of Pretoria, 2012.
Biochemistry
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27

Lövkvist, Wallström Eva. "On the regulation of ornithine decarboxylase." Lund : Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/68945009.html.

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28

Niemand, Jandeli. "A phage display study of interacting peptide binding partners of malarial S-Adenosylmethionine decarboxylase/Ornithine decarboxylase." Diss., University of Pretoria, 2007. http://hdl.handle.net/2263/24105.

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Due to the increasing resistance against the currently used antimalarial drugs, novel chemotherapeutic agents that target new metabolic pathways for the treatment of malarial infections are urgently needed. One approach to the drug discovery process is to use interaction analysis to find proteins that are involved in a specific metabolic pathway that has been identified as a drug target. Protein-protein interactions in such a pathway can be preferential targets since a) there is often greater structural variability in protein-protein interfaces, which can lead to more effective differentiation between the parasite and host proteins; and b) the important amino acids in a protein-protein interface are often conserved and even one amino acid mutation can lead to the dissociation of the complex, implying that resistance should be slower to appear. Since polyamines and their biosynthetic enzymes occur in increased concentrations in rapidly proliferating cells, the inhibition of polyamine metabolism is a rational approach for the development of antiparasitic drugs. Polyamine synthesis in P. falciparum is uniquely facilitated by a single open reading frame that encodes both rate-limiting enzymes in the pathway, namely ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). The AdoMetDC/ODC domains are assembled in a heterotetrameric bifunctional protein complex of ~330 kDa. Inhibition of both decarboxylase activities is curative of murine malaria and indicates the viability of such strategies in malaria control. It was hypothesized that protein ligands to this enzyme can be utilized in targeting the polyamine biosynthetic pathway in a novel approach. The bifunctional PfAdoMetDC/ODC was recombinantly expressed with a C-terminal Strep-tag-II to allow affinity purification. Subsequent gel electrophoresis analysis showed the presence of 3 contaminating proteins (~60 kDa, ~70 kDa and ~112 kDa) that co-elute with the ~330 kDa AdoMetDC/ODC. Efforts to purify the bifunctional protein to homogeneity included subcloning into a double-tagged vector for tandem affinity purification as well as size-exclusion HPLC. SDS-PAGE analysis of these indicated that separation of the four proteins was not successful, implicating the presence of strong protein-protein interactions. Western blot analysis showed that the ~112 kDa and ~70 kDa peptides were recombinantly produced with a C-terminal Strep-tag, indicating their heterologous origin. The ~60 kDa fragment was however not recognised by the tag-specific antibodies. This implies that this fragment is of E. coli origin. MS-analysis of the contaminating bands showed that the ~112 kDa peptide is an N-terminally truncated form of the full-length protein, the ~70 kDa peptide is a mixture of N-terminally truncated recombinant protein and E. coli DnaK and the ~60 kDa peptide is E. coli GroEL. A P. falciparum cDNA phage display library was used to identify peptide ligands to PfAdoMetDC/ODC. Of the peptides isolated through the biopanning process, only one was shown to occur in vivo. It could however not be conclusively shown that the isolated peptides bind to PfAdoMetDC/ODC and not to the co-eluting E. coli proteins. It is thought that while it is extremely likely that interacting protein partners to PfAdoMetDC/DOC exist, the available technologies are not sufficient to lead to the identification of such partners.
Dissertation (MSc (Biochemistry))--University of Pretoria, 2008.
Biochemistry
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29

Blaesse, Michael. "Kristallstrukturanalyse von homooligomeren, Flavin-enthaltenden Cystein-Decarboxylasen." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964589222.

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30

Cheung, Wing Yee. "A yeast pyruvate decarboxylase regulatory gene." Thesis, Imperial College London, 1985. http://hdl.handle.net/10044/1/37659.

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31

Webb, Michael Edward. "Mechanistic studies on aspartate α-decarboxylase." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616065.

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32

Kern, Andrew David. "Structure of ornithine decarboxylase from mouse /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.

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33

Van, Brummelen Anna Catharina. "Functional genomics analysis of the effects of co-inhibition of the malarial S-adenosylmethionine decarboxylase/ornithine decarboxylase." Thesis, University of Pretoria, 2008. http://hdl.handle.net/2263/25135.

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Polyamines are ubiquitous components of all living cells and their depletion usually causes growth arrest or cytostasis, a strategy employed for treatment of West-African trypanosomiasis. In the malaria parasite, Plasmodium falciparum, polyamine biosynthesis is regulated by the uniquely bifunctional protein, Sadenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC). The unique nature of this protein could provide a selective mechanism for antimalarial treatment. To validate polyamine depletion and specifically PfAdoMetDC/ODC, as drug target for antimalarial therapeutic intervention, polyamine biosynthesis was completely restrained via the inhibition of both catalytic sites of PfAdoMetDC/ODC with DFMO and MDL73811. The physiological effects during the resulting cytostasis were studied with a comprehensive functional genomics approach. The study was preceded by various assays to determine the treatment dosage that would result in complete cytostasis, without non-specific chemical cytotoxicity. The results obtained revealed that the cytostatic mechanism with growth arrest of the treated parasites and normal progression of the untreated controls require special consideration for basic comparisons of response in terms of the assay methodology used and data analysis. This is particularly important when studying a multistage organism such as P. falciparum, which constantly develops and change during the intraerythrocytic developmental cycle, such that growth arrest compared to normal progression would result in significant differences merely due to stage. This critical principle was kept in mind throughout the investigation and was applied to the relative quantification of RNA, proteins and metabolites via a relative time zero approach as opposed to the standard parallel time point comparison. Three independent functional genomics investigations, namely transcriptomics, proteomics and metabolomics were conducted, in which highly synchronised 3D7 parasite cultures were treated during the schizont stage and parasites were sampled during a time course at three time points (just before and during cytostasis). Transcriptome analysis revealed the occurrence of a generalised transcriptional arrest just prior to the growth arrest. To our knowledge this is the first time that transcriptional arrest as the preceding mechanism of cytostasis due to polyamine depletion, was demonstrated. However, despite the transcriptional arrest, the abundance of 538 transcripts was differentially affected and included three perturbation-specific compensatory transcriptional responses: the increased abundance of the transcripts for lysine decarboxylase and ornithine aminotransferase (OAT) and the decreased abundance of that for S-adenosylmethionine synthetase (AdoMet synthetase). Pearson correlations indicated more subtle effects of the perturbation on the proteome and even more so on the metabolome where homeostasis was generally maintained, except downstream to the enzymatic blockade at PfAdoMetDC/ODC. The perturbation-specific compensatory roles of OAT in the regulation of ornithine and AdoMet synthetase in the regulation of AdoMet were confirmed on both the protein and metabolite levels, confirming their biological relevance. The results provide evidence that P. falciparum respond to alleviate the detrimental effects of polyamine depletion via the regulation of its transcriptome and subsequently the proteome and metabolome, which supports a role for transcriptional control in the regulation of polyamine and methionine metabolism within the parasite. The study concludes that polyamines are essential molecules for parasite survival and that PfAdoMetDC/ODC is a valid target for antimalarial drug development.
Thesis (PhD)--University of Pretoria, 2008.
Biochemistry
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34

Van, Brummelen Anna Catharina. "Functional genomics analysis of the effects of co-inhibition of the malarial S-adenosylmethionine decarboxylase/ornithine decarboxylase." Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-05302009-124548.

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35

Nancarrow, Michelle Jane. "The role of polyamines in cellular and molecular events in the wool follicle." Title page, contents and abstract only, 1995. http://web4.library.adelaide.edu.au/theses/09PH/09phn1756.pdf.

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Bibliography: leaves 255-280. In vivo and in vitro investigations of the hypothesis that polyamines and their synthetic enzymes have a role in regulation of cellular and molecular processes in the follicle. The activity of ornithine decarboxylase (ODC), the rate limiting polyamine biosynthetic enzyme, is demonstrated in wool follicle homogenates.

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36

Almrud, Jeffrey James. "Structural investigations of E. coli biosynthetic arginine decarboxylase, and crystal structure of human ornithine decarboxylase ar 2.1Å resolution /." Digital version accessible at:, 2000. http://wwwlib.umi.com/cr/utexas/main.

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37

Sunde, Margaret. "N-terminal modification of S-adenosylmethionine decarboxylase." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318198.

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38

Hall, Andrea. "Bacillus subtilis oxalate decarboxylase : roles and regulation." Thesis, University of East Anglia, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426696.

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39

Illingworth, Crista. "Isolation of plant orthinine decarboxylase - interacting proteins." Thesis, University of East Anglia, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327587.

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40

Kathiara, Mona. "Characterisation of oxalate decarboxylase from Agaricus bisporus." Thesis, University of Westminster, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263931.

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41

White, Mark. "Biochemical characterisation of a novel decarboxylase system." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/biochemical-characterisation-of-a-novel-decarboxylase-system(cb24497e-a0f8-45de-8da6-5b5a057206c0).html.

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The Fdc1 and Pad1 decarboxylase system from Saccharomyces cerevisiae has been identified as a potential candidate to feature in novel biofuel production pathways based on its ability to catalyze the transformation of sorbic acid, an antimicrobial compound, to 1, 3-pentadiene, a volatile hydrocarbon. Although information on the system is currently insufficient to permit a full assessment of its potential for future commercialization, it is hoped that (rational) engineering approaches can be used to evolve the enzymes to produce more desirable hydrocarbons. This requires biochemical characterization of the proteins. Genetic manipulation experiments have indicated that both enzymes are required for activity. However, no in vitro studies were conducted to verify the function, determine the relationship or establish the cofactor requirements of Fdc1 and Pad1. Results reported here establish that Fdc1 is the enzyme responsible for catalyzing decarboxylation, requiring a novel cofactor synthesized by Pad1 (or the bacterial homologue UbiX) for activity. High resolution crystal structures and mass spectrometry data from Fdc1 co-expressed with UbiX have indicated that the cofactor corresponds to a modified flavin mononucleotide (FMN) that has been extended with a C5-unit through linkages at the N5 and C6 atoms, creating a fourth, non-aromatic ring on the isoalloxazine group. Subsequent solution studies have established that this modification is achieved through isoprene chemistry, with UbiX facilitating prenyl transfer from dimethylallyl monophosphate (DMAP) to FMN. Analysis of wild type and mutant UbiX constructs by kinetic X-ray crystallography has allowed several distinct stages of the prenyl transfer reaction to be trapped, establishing that the protein uses a number of chemical strategies similar to terpene synthases to generate its product. The active site is dominated by pi systems, which aid heterolytic cleavage of the isoprene precursors phosphate-C1’ bond following FMN reduction, leading to the formation of an N5-C1’ intermediate. UbiX then acts as a chaperone for adduct reorientation, potentially via a transient tertiary carbocation, ultimately resulting in ring closure between the C6 and C3’. This work has established the biochemical principles underpinning the Fdc1 and Pad/UbiX decarboxylase system, providing a platform from which rational evolution approaches can be applied to the enzymes, specifically Fdc1, to improve their validity in the biofuels industry. It has also identified a novel cofactor that extends the previously well-documented flavin and isoprenoid repertoire.

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42

Brown, Audrey Elaine. "Constructing a recombinant model of the human pyruvate dehydrogenase complex." Thesis, University of Glasgow, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248119.

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43

Yu, Daria Hil Ching. "Inactivation of benzoylformate decarboxylase by thiamin thiazolone diphosphate." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58762.pdf.

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44

Saleh, Lana Y. "Orotidine-5'-Monophosphate Decarboxylase: Purification and Spectral Studies." Youngstown State University / OhioLINK, 1999. http://rave.ohiolink.edu/etdc/view?acc_num=ysu999190551.

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45

Roberts, Rick Lee. "Structural and bioinformatic analysis of ethylmalonyl-CoA decarboxylase." Thesis, State University of New York at Buffalo, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1600817.

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Many enzymes of the major metabolic pathways are categorized into superfamilies which share common folds. Current models postulate these superfamilies are the result of gene duplications coupled with mutations that result in the acquisition of new functions. Some of these new functions are considered advantageous and selected for, while others may simply be tolerated. The latter can result in metabolites being produced at low rates that are of no known use by the cell, and can become toxic when accumulated. Concurrent with the evolution of this tolerable or potentially detrimental metabolism, organisms are selected to evolve a means of correcting or “proofreading” these non-canonical metabolites to counterbalance their detrimental effects. Metabolite proofreading is a process of intermediary metabolism analogous to DNA proof reading that acts on these abnormal metabolites to prevent their accumulation and toxic effects.

Here we structurally characterize ethylmalonyl-CoA decarboxylase (EMCD), a member of the family of enoyl-CoA hydratases within the crotonase superfamily of proteins, which is coded by the ECHDC1 (enoyl-CoA hydratase domain containing 1) gene. EMCD has been shown to have a metabolic proofreading property, acting on the metabolic byproduct ethylmalonyl-CoA to prevent its accumulation which could result in oxidative damage. We use the complimentary methods of in situ crystallography, small angle X-ray scattering, and single crystal X-ray crystallography to structurally characterize EMCD, followed by homology analysis in order to propose a mechanism of action. This represents the first structure of a crotonase superfamily member thought to function as a metabolite proof reading enzyme.

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46

Chu, Yi-wen 1962. "Amino acid sequence requirements for ornithine decarboxylase activity." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/276838.

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ODC activity of the altered proteins was measured and compared to that of the full length 461 amino acid containing ODC. Mouse ODC cDNA sequences were deleted from either 5' or 3' ends using exonuclease III and Mung Bean nuclease treatments. An internal deletion was obtained by Hinc II and Bcl I restriction endonuclease digestion of the full length ODC cDNA. Capped mRNAs were synthesized in vitro using the resulting deleted DNA as templates, and the protein was translated in vitro. The results indicate that the protein in which translation initiates at internal AUG start codons does not have any activity. The protein with 39 amino acids deleted from carboxy-terminus maintains 12% of the activity, while deletion of greater than 79 amino acids have no activity. An internal deletion from amino acid 290 to 331 and which may contain the suspected ornithine binding site has no activity. These results suggest that the entire amino acid sequence of mouse ODC is required for full activity of the enzyme.

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47

Tome, Margaret Ellen. "Cellular and biochemical consequences of ornithine decarboxylase regulation." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/282137.

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The polyamines are abundant polycations necessary for eucaryotic cell growth. Ornithine decarboxylase (ODC), the first and often rate-limiting enzyme in polyamine biosynthesis, is responsible for the formation of putrescine, the precursor for polyamine synthesis. ODC is normally very tightly regulated by a complex interaction of control of both synthesis and degradation. Regulation of ODC synthesis allows cells to increase ODC in response to various stimuli; however, the importance of the rapid degradation of ODC in cellular metabolism is less well understood. The studies presented here have compared the parental, HTC cells, which exhibit rapid ODC degradation, to two cell lines, DH23A and HMOA, which express a more stable ODC, to examine the cellular consequences of aberrant ODC expression. Aberrantly elevated ODC in DH23A cells results in a dramatic accumulation of endogenous putrescine, a decrease in cell number and the appearance of apoptotic cells. In contrast, HTC cells, with moderate polyamine contents, can be maintained in exponential growth. Accumulation of similar concentrations of putrescine from an exogenous source mimics the effect of ODC overexpression. This suggests that putrescine is the causative agent or trigger of apoptosis. Accumulation of excess intracellular putrescine inhibits the formation of modified eIF-5A in vivo. eIF-5A is a protein that is post-translationally modified by spermidine. Although the function is unclear, both eIF-5A and the modification by spermidine are necessary for growth in eucaryotic cells. Treatment of DH23A cells with diaminoheptane(DAH), an in vitro inhibitor of eIF-5A modification, both inhibits the modification of eIF-5A in vivo and increases apoptosis. DAH appears to cause a decrease in cell number by acting as a competitive inhibitor of the post-translational modification of eIF-5A by spermidine. Putrescine probably inhibits the formation of modified eIF-5A upstream of the spermidine addition, but not at the level of transcription. These data support the hypothesis that the rapid degradation of ODC may be a protective mechanism to avoid cell toxicity due to putrescine accumulation and suggest that suppression modified eIF-5A formation is one mechanism by which cells may be induced to undergo apoptosis.

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48

Rose, Janet Elizabeth. "Mechanistic studies on glutamate decarboxylase and serine hydroxmethyltransferase." Thesis, University of St Andrews, 1993. http://hdl.handle.net/10023/14295.

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(2S)- and (2R)-Serine O-sulphate have been synthesised and shown to inactivate glutamate decarboxylase (GAD) from E. Coli. Novel methodology was developed to enable the stereospecific synthesis of (2S) and (2R)-deuteriated serine in order to probe the mechanism of inactivation. The rates of inactivation of glutamate decarboxylase by (2S)-, (2S)-[2-2H]-, (2R)- and (2R)-[2-2H]-serine O-sulphate have been measured for each of the isotopomers at a range of concentrations. From the data obtained the deuterium isotope effects were determined for each enantiomer. The inactivation by the (2S)-enantiomer was shown to involve C-H bond cleavage while inactivation by the (2R)-isomer involves C-decarboxylation. Both processes were shown to occur on the 4'-re-face of the coenzyme, the opposite face to that utilised in the physiological decarboxylation reaction. The methodology developed for the synthesis of the deuteriated serines involved the regiospecific introduction of deuterium to the C-6 centre of (3R)- and (3S)-2,5- dimethoxy-3-isopropyl-3,6-dihydropyrazine. Schollkopf chemistry was then exploited for the stereospecific alkylation at C-6 of the dihydropyrazines. This chemistry was versatile and enabled the synthesis of other deuteriated amino acids. For example (2S)-[2-2H]-phenylalanine, (2S)-[2-2H]-allylglycine and (2S)-[2-2H]-aspartic acid were synthesised using this chemistry. The decarboxylation of 2-aminomalonic acid by cytosolic serine hydroxymethyltransferase (SHMT) was studied. Contrary to previous reports, the reaction was found to be stereospecific and the newly introduced hydrogen was shown to occupy the 2-pro-S position of the glycine product.

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Nilsson, Tatjana. "Amyloid precursor protein: cellular studies and animal models /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-832-0/.

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De, Villiers Jandré. "Attempted routes towards the synthesis of fluorinated analogues of ornithine as potential inhibitors of ornithine decarboxylase /." Link to the online version, 2007. http://hdl.handle.net/10019/417.

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Dissertations / Theses on the topic 'Decarboxylases'

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