Towards an understanding of the functional significance of N-terminal domain divergence in human AMP deaminase isoforms

Sabina, Richard L.; Mahnke-Zizelman, Donna K.

doi:10.1016/s0163-7258(00)00040-1

Cited by 33 publications

(20 citation statements)

References 46 publications

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“…AMPD1 plays a major role in regulating cellular AMP levels by converting AMP to IMP and competes with cytosolic 5Ј-nucleotidases for available AMP (43). Defects in the AMPD1 gene decrease enzyme activity and increase AMP accumulation in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Suppression of 5′-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle

Kulkarni

Karlsson

Szekeres

et al. 2011

Journal of Biological Chemistry

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Background: The 5Ј-nucleotidase (NT5) family of enzymes dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. Results: NT5 silencing increases the intracellular availability of AMP/ATP and invokes AMP-activated protein kinase (AMPK) activation, glucose uptake, and lipid oxidation. Conclusion: NT5C enzymes inhibit basal lipid oxidation and glucose transport in skeletal muscle. Significance: Suppression of cytosolic NT5C expression or activity may bypass metabolic inflexibility in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Suppression of 5′-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle

Kulkarni

Karlsson

Szekeres

et al. 2011

Journal of Biological Chemistry

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“…However, two yeast proteins of unknown function (Ybr284p and Yjl070p) are .30% identical to Amd1p in their C terminus (supporting information, Figure S1) (Duenas et al 1999;Vandenbol and Portetelle 1999). Strikingly, in most organisms, AMPD isoforms have a highly divergent N terminus and in several cases, including yeast, the N terminus of the protein is not required for activity and is often lost during protein purification due to proteolysis (Merkler et al 1989;Sabina and Mahnke-Zizelman 2000). Yeast AMP deaminase activity has been characterized in vitro (Meyer et al 1989) and is presumed to be high under specific growth conditions where massive synthesis of IMP from AMP has been observed (Osorio et al 2003;Silles et al 2005;Loret et al 2007).…”

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confidence: 99%

Phenotypic Consequences of Purine Nucleotide Imbalance inSaccharomyces cerevisiae

et al. 2009

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Coordinating homeostasis of multiple metabolites is a major task for living organisms, and complex interconversion pathways contribute to achieving the proper balance of metabolites. AMP deaminase (AMPD) is such an interconversion enzyme that allows IMP synthesis from AMP. In this article, we show that, under specific conditions, lack of AMPD activity impairs growth. Under these conditions, we found that the intracellular guanylic nucleotide pool was severely affected. In vivo studies of two AMPD homologs, Yjl070p and Ybr284p, indicate that these proteins have no detectable AMP, adenosine, or adenine deaminase activity; we show that overexpression of YJL070c instead mimics a loss of AMPD function. Expression of the yeast transcriptome was monitored in a AMPD-deficient mutant in a strain overexpressing YJL070c and in cells treated with the immunosuppressive drug mycophenolic acid, three conditions that lead to severe depletion of the guanylic nucleotide pool. These three conditions resulted in the up-or downregulation of multiple transcripts, 244 of which are common to at least two conditions and 71 to all three conditions. These transcriptome results, combined with specific mutant analysis, point to threonine metabolism as exquisitely sensitive to the purine nucleotide balance.T HE purine nucleotides, ATP and GTP, are involved in almost all aspects of cellular life. In addition to their role as building blocks of nucleic acids, adenylic and guanylic nucleotides have specific roles. For example, GTP is critical for translation and for signaling through GTPases, while ATP is the major energyproviding molecule in the cell. In yeast, intracellular concentrations of ATP and GTP are clearly different ($5 and 1.5 mm, respectively; Breton et al. 2008;Gauthier et al. 2008), most probably as the result of regulatory processes that maintain homeostasis. In most eukaryotic cells, including yeast, adenylic and guanylic nucleotides either are synthesized from a common precursor (IMP) or are recycled from preformed bases or nucleosides (Figure 1). While most enzymes involved in these processes have been identified, the physiological consequences of purine nucleotide imbalance are far from being understood. Interestingly, drugs specifically inhibiting GTP synthesis, such as mycophenolic acid (MPA), have a strong immunosuppressive effect and are now widely used to limit allograft rejection. We have previously established the effect of MPA on the yeast proteome and have identified numerous yeast mutants hypersensitive to this drug (Desmoucelles et al. 2002). MPA effects are due to GTP shortage, since they are reversed by exogenous guanine, allowing replenishment of the GTP pool. However, drugs often have secondary effects and can be detoxified and/or diluted during cell growth. As an alternative, consequences of purine nucleotide imbalance can be investigated using yeast mutants. In two previous studies, we have used specific mutants to increase the GTP pool or decrease the ATP pool (Breton et al. 2008;Gauthier et al. 20...

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“…The increase in residual activity at 0, 12.5, and 25°C in the study by Raffin and Leray (1979) can be explained by the proteolysis of AMP deaminase which could cause a possible activation. The AMP deaminase is an unstable enzyme that is frequently hydrolyzed during purification by means of protease enzymes (Sabina and Mahnke-Zizelman, 2000). The fact that AMP deaminase of jumbo squid mantle is resistant to proteolysis (Marquez-Rios et al, 2008) could be because it is different from AMP deaminase isolated from vertebrate organisms.…”

Section: Temperature Stabilitymentioning

confidence: 99%

Partial Characterization of AMP Deaminase from Jumbo Squid (Dosidicus gigas) Mantle

Pacheco‐Aguilar

Ezquerra‐Brauer

Castillo-Yañez

et al. 2009

Journal of Aquatic Food Product Technology

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AMP deaminase enzyme showed an optimum temperature at 35°C. It was relatively stable between 30 and 40°C but extremely unstable at higher temperatures. The optimum pH was 6.0 and the enzyme presented an excellent stability with pH between 5.5 and 6.5. The K + ion acted as a negative effector when used in concentrations higher than 50 mM. The nucleotide ATP acted as a positive effector in concentrations exceeding 2 mM, while ADP was a positive effector between 0 and 2 mM. These results indicated that AMP deaminase is an important enzyme in Dosidicus gigas post-mortem biochemistry, involving the rapid degradation of AMP during iced storage of jumbo squid mantle.

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Towards an understanding of the functional significance of N-terminal domain divergence in human AMP deaminase isoforms

Cited by 33 publications

References 46 publications

Suppression of 5′-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle

Suppression of 5′-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle

Phenotypic Consequences of Purine Nucleotide Imbalance inSaccharomyces cerevisiae

Partial Characterization of AMP Deaminase from Jumbo Squid (Dosidicus gigas) Mantle

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