Purine salvage inMethanocaldococcus jannaschii: Elucidating the role of a conserved cysteine in adenine deaminase

Perhaps the simplest realization of tissue engineering involves the direct administration of a suspension of engineered cells—cells that have been isolated, characterized, manipulated, and amplified outside of the body. One can imagine engineering diverse and useful properties into the injected cells: functional enzymes, secretion of drugs, resistance to immune recognition, and growth control. We are most familiar with methods for manipulating the cell internal chemistry by introduction or removal of genes; for example, the first gene therapy experiments involved cells that were engineered to produce a deficient enzyme, adenine deaminase (see Chapter 2). But genes also encode systems that enable cell movement, cell mechanics, and cell adhesion. Conceivably, these systems can be modified to direct the interactions of an administered cell with its new host. For example, cell adhesion signals could be introduced to provide tissue targeting, cytoskeleton-associated proteins could be added to alter viscosity and deformability (in order to prolong circulation time), and motor proteins could be added to facilitate cell migration. Ideally, cell fate would also be engineered, so that the cell would move to the appropriate location in the body, no matter how it was administered; for example, transfused liver cells would circulate in the blood and, eventually, crawl into the liver parenchyma. Cells find their place in developing organisms by a variety of chemotactic and adhesive signals, but can these same signaling mechanisms be engaged to target cells administered to an adult organism? We have already considered the critical role of cell movement in development in Chapter 3. In this chapter, the utility of cell trafficking in tissue engineering is approached by first considering the normal role of cell recirculation and trafficking within the adult organism. Most cells can be easily introduced into the body by intravenous injection or infusion. This procedure is particularly appropriate for cells that function within the circulation; for example, red blood cells (RBCs) and lymphocytes. The first blood transfusions into humans were performed by Jean-Baptiste Denis, a French physician, in 1667. This early appearance of transfusion is startling, since the circulatory system was described by William Harvey only a few decades earlier, in 1628.

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The role of the NTPDase enzyme family in parasites: what do we know, and where to from here?

Parasitology ◽

10.1017/s003118201200025x ◽

2012 ◽

Vol 139 (8) ◽

pp. 963-980 ◽

Cited By ~ 28

Author(s):

FIONA M. SANSOM

Keyword(s):

Legionella Pneumophila ◽

Sugar Transport ◽

Protein Glycosylation ◽

Future Research ◽

Nucleoside Triphosphate ◽

Purine Salvage ◽

Diverse Range ◽

Protein Superfamily ◽

Eukaryotic Organisms

SUMMARYNucleoside triphosphate diphosphohydrolases (NTPDases, GDA1_CD39 protein superfamily) play a diverse range of roles in a number of eukaryotic organisms. In humans NTPDases function in regulating the inflammatory and immune responses, control of vascular haemostasis and purine salvage. In yeast NTPDases are thought to function primarily in the Golgi, crucially involved in nucleotide sugar transport into the Golgi apparatus and subsequent protein glycosylation. Although rare in bacteria, in Legionella pneumophila secreted NTPDases function as virulence factors. In the last 2 decades it has become clear that a large number of parasites encode putative NTPDases, and the functions of a number of these have been investigated. In this review, the available evidence for NTPDases in parasites and the role of these NTPDases is summarized and discussed. Furthermore, the processes by which NTPDases could function in pathogenesis, purine salvage, thromboregulation, inflammation and glycoconjugate formation are considered, and the data supporting such putative roles reviewed. Potential future research directions to further clarify the role and importance of NTPDases in parasites are proposed. An attempt is also made to clarify the nomenclature used in the parasite field for the GDA1_CD39 protein superfamily, and a uniform system suggested.

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The pivotal role of guanine phosphoribosyltransferase in purine salvage by Giardia lamblia

Molecular Microbiology ◽

10.1046/j.1365-2958.2002.02942.x ◽

2002 ◽

Vol 44 (4) ◽

pp. 1073-1079 ◽

Cited By ~ 10

Author(s):

Narsimha Munagala ◽

Ching C. Wang

Keyword(s):

Giardia Lamblia ◽

Pivotal Role ◽

Purine Salvage

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The role of liver Na+/purine nucleoside cotransporter in purine salvage for extrahepatic tissues Physiology, Tufts, Boston

Hepatology ◽

10.1016/0270-9139(95)94975-5 ◽

1995 ◽

Vol 22 (4) ◽

pp. A313

Keyword(s):

Purine Nucleoside ◽

Purine Salvage ◽

Extrahepatic Tissues

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Listeria monocytogenes relA and hpt Mutants Are Impaired in Surface-Attached Growth and Virulence

Journal of Bacteriology ◽

10.1128/jb.184.3.621-628.2002 ◽

2002 ◽

Vol 184 (3) ◽

pp. 621-628 ◽

Cited By ~ 99

Author(s):

Clare M. Taylor ◽

Mark Beresford ◽

Harry A. S. Epton ◽

David C. Sigee ◽

Gilbert Shama ◽

...

Keyword(s):

Listeria Monocytogenes ◽

Stringent Response ◽

Physiological Adaptation ◽

Salvage Pathway ◽

Purine Salvage ◽

Biofilm Growth ◽

Transposon Insertion ◽

New Information

ABSTRACT We describe here the identification and characterization of two Listeria monocytogenes (Tn917-LTV3) relA and hpt transposon insertion mutants that were impaired in growth after attachment to a model surface. Both mutants were unable to accumulate (p)ppGpp in response to amino acid starvation, whereas the wild-type strain accumulated (p)ppGpp within 30 min of stress induction. The induction of transcription of the relA gene after adhesion was demonstrated, suggesting that the ability to mount a stringent response and undergo physiological adaptation to nutrient deprivation is essential for the subsequent growth of the adhered bacteria. The absence of (p)ppGpp in the hpt mutant, which is blocked in the purine salvage pathway, is curious and suggests that a functional purine salvage pathway is required for the biosynthesis of (p)ppGpp. Both mutants were avirulent in a murine model of listeriosis, indicating an essential role for the stringent response in the survival and growth of L. monocytogenes in the host. Taken as a whole, this study provides new information on the role of the stringent response and the physiological adaptation of L. monocytogenes for biofilm growth and pathogenesis.

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Novel biochemical pathways in parasitic protozoa

Parasitology ◽

10.1017/s003118200008344x ◽

1989 ◽

Vol 99 (S1) ◽

pp. S93-S112 ◽

Cited By ~ 97

Author(s):

A. H. Fairlamb

Keyword(s):

Metabolic Pathways ◽

Acid Metabolism ◽

Mammalian Host ◽

Purine Salvage ◽

Biochemical Pathways ◽

Thiol Metabolism ◽

End Products ◽

Folic Acid Metabolism ◽

Anaerobic Protozoa

SUMMARYThroughout evolution, enzymes and their metabolites have been highly conserved. Parasites are no exception to this and differ most markedly by the absence of metabolic pathways that are present in the mammalian host. In general, parasites are metabolically lazy and rely on the metabolism of the host both for a supply of prefabricated components such as purines, fatty acids, sterols and amino acids and for the removal of end-products. Nonetheless, parasites are metabolically highly sophisticated in that (1) they retain the genetic capacity to induce many pathways, when needed, and (2) they have developed complex mechanisms for their survival in the host. Certain unique features of the metabolism of trypanosomes, leishmania, malaria and anaerobic protozoa will be discussed. This will include (1) glycolysis and electron transport with reference to the unique organelles: the glycosome and the hydrogenosome, (2) purine salvage, pyrimidine biosynthesis and folic acid metabolism and (3) polyamine and thiol metabolism with special reference to the role of the unique metabolite of trypanosomes and leishmanias, trypanothione.

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