Biosynthesis of myo-inositol in rat mammary gland. Isolation and properties of the enzymes

Naccarato, William F.; Ray, Rita E.; Wells, William W.

doi:10.1016/0003-9861(74)90022-8

Cited by 113 publications

(35 citation statements)

References 22 publications

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“…Mammalian inositol monophosphatases have been shown to have a relatively broad substrate specificity and can hydrolyze a variety of phosphate compounds other than inositol monophosphatase (6,7,11,16,24,37). For instance, the enzyme from rat testis hydrolyzes adenosine 2Ј-monophosphate with a relative velocity of 38% (6) and the enzyme from bovine brain hydrolyzes ␤-glycerophosphate and adenosine 2Ј-monophosphate with relative velocities of 33 and 50%, respectively (7).…”

Section: Resultsmentioning

confidence: 99%

Inositol monophosphatase activity from the Escherichia coli suhB gene product

et al. 1995

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The suhB gene is located at 55 min on the Escherichia coli chromosome and encodes a protein of 268 amino acids. Mutant alleles of suhB have been isolated as extragenic suppressors for the protein secretion mutation (secY24), the heat shock response mutation (rpoH15), and the DNA synthesis mutation (dnaB121) (K. Shiba, K. Ito, and T. Yura, J. Bacteriol. 160:696-701, 1984; R. Yano, H. Nagai, K. Shiba, and T. Yura, J. Bacteriol. 172:2124-2130, 1990; S. Chang, D. Ng, L. Baird, and C. Georgopoulos, J. Biol. Chem. 266:3654-3660, 1991). These mutant alleles of suhB cause cold-sensitive cell growth, indicating that the suhB gene is essential at low temperatures. Little work has been done, however, to elucidate the role of the product of suhB in a normal cell and the suppression mechanisms of the suhB mutations in the aforementioned mutants. The sequence similarity shared between the suhB gene product and mammalian inositol monophosphatase has prompted us to test the inositol monophosphatase activity of the suhB gene product. We report here that the purified SuhB protein showed inositol monophosphatase activity. The kinetic parameters of SuhB inositol monophosphatase (K m ‫؍‬ 0.071 mM; V max ‫؍‬ 12.3 mol/min per mg) are similar to those of mammalian inositol monophosphatase. The ssyA3 and suhB2 mutations, which were isolated as extragenic suppressors for secY24 and rpoH15, respectively, had a DNA insertion at the 5 proximal region of the suhB gene, and the amount of SuhB protein within mutant cells decreased. The possible role of suhB in E. coli is discussed.The suhB gene was first identified as the locus for the ssyA3(Cs) mutation that was isolated as an extragenic suppressor for the secY24(Ts) mutant (31). The ssyA3 mutation restored the defect in protein secretion caused by the secY24 mutation (33) and rescued the temperature-sensitive cell growth of secY24 mutant cells. The ssyA3 mutation caused cold-sensitive cell growth by itself and impaired protein synthesis was observed in the ssyA3 mutant at low temperatures (31). The cold-sensitive growth of the ssyA3 mutant was rescued by introduction of the wild-type copy of suhB, indicating that ssyA3 is a mutant allele of suhB (40). The suhB2(Cs) mutation is another allele of suhB and was isolated as an extragenic suppressor of the rpoH15(Ts) mutation. The rpoH15 mutant gene produces an altered 32 protein and causes a defect in the induction of heat shock proteins at higher temperatures (42). The suhB2(Cs) mutation rescued the temperature-sensitive cell growth of the rpoH15 mutant and partially restored heat shock induction in the mutant cell (40). A coldsensitive mutation was also mapped in the suhB locus as an extragenic suppressor for the dnaB121(Ts) mutation that inhibits replication of phage (2). Thus, mutant alleles of suhB have effects on diverse cell activities, including protein export, stress response, and DNA replication.The suhB gene encodes a protein of 268 amino acids (40), and the primary structure of its translated product shows a high level of similarity t...

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Section: Resultsmentioning

confidence: 99%

Inositol monophosphatase activity from the Escherichia coli suhB gene product

et al. 1995

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“…Indeed, IMPase purified from a variety of sources was subsequently shown to be inhibited by Li þ with half maximal activity seen at 0.8 mM. 5,6 Li þ acts via an uncompetitive inhibition mechanism 6 -an unusual form of inhibition caused by Li þ binding the enzyme-substrate complex. It does this by displacing a Mg 2 þ ion from the active site and prevents release of the phosphate after hydrolysis from InsP 1 .…”

Section: þ and Inositol-depletionmentioning

confidence: 99%

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

2004

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Inositol, a simple six-carbon sugar, forms the basis of a number of important intracellular signaling molecules. Over the last 35 years, a series of biochemical and cell biological experiments have shown that lithium (Li þ ) reduces the cellular concentration of myo-inositol and as a consequence attenuates signaling within the cell. Based on these observations, inositol-depletion was proposed as a therapeutic mechanism in the treatment of bipolar mood disorder. Recent results have added significant new dimensions to the original hypothesis. However, despite a number of clinical studies, this hypothesis still remains to be either proven or refuted. In this review of our current knowledge, I will consider where the inositol-depletion hypothesis stands today and how it may be further investigated in the future.

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“…In mammals, this group includes at least four related phosphomonoesterases (the best known of which is inositol monophosphatase), the metabolic enzyme phosphoglucomutase, and the multifunctional enzyme glycogen synthase kinase-3 (GSK-3) (Gould et al, 2004c;Klein and Melton, 1996;Naccarato et al, 1974;Ray et al, 1978;Stambolic et al, 1996;York et al, 1995). The 1996 discovery that lithium inhibits GSK-3 raised the question of whether that inhibition might be relevant to the therapeutic consequences of lithium administration (Klein and Melton, 1996;Stambolic et al, 1996); however, the specific relation of this inhibition to the mood stabilizing properties of lithium is still unclear.…”

Section: Introductionmentioning

confidence: 99%

β-Catenin Overexpression in the Mouse Brain Phenocopies Lithium-Sensitive Behaviors

Gould

Einat

O’Donnell

et al. 2007

Neuropsychopharmacol

128

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Lithium inhibits glycogen synthase kinase-3 (GSK-3) at therapeutic concentrations; however, it is unclear if this inhibition and its downstream effects on specific signaling pathways are relevant to the treatment of bipolar disorder and depression. One of the targets of GSK-3 is the transcription factor b-catenin. Normally active GSK-3 phosphorylates b-catenin, leading to its degradation. Inhibition of GSK-3 therefore increases b-catenin. We have utilized transgenic mice to investigate the behavioral consequences of CNS b-catenin overexpression. Transgenic mice overexpressing b-catenin demonstrated behavioral changes similar to those observed following the administration of lithium, including decreased immobility time in the forced swim test (FST). Further, we show that although acute administration of lithium and overexpression of the b-catenin transgene inhibits d-amphetamine-induced hyperlocomotion, neither lithium nor the b-catenin transgene prevents d-amphetamine-induced sensitization, as measured by locomotor activity. Both lithiumtreated and b-catenin mice had an elevated response to d-amphetamine following multiple administrations of the stimulant, though the difference in absolute locomotion was maintained throughout the sensitization time-course. Neither acute lithium nor b-catenin overexpression had an effect on d-amphetamine-induced stereotyped behavior. The results of this study, in which b-catenin transgenic mice exhibited behaviors identical to those observed in lithium-treated mice, are consistent with the hypothesis that the behavioral effects of lithium in these models are mediated through its direct inhibition of GSK-3 and the consequent increase in b-catenin. By associating the behavioral effects of lithium with b-catenin levels, these data suggest that increasing b-catenin might be a novel therapeutic strategy for mood disorders.

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Biosynthesis of myo-inositol in rat mammary gland. Isolation and properties of the enzymes

Cited by 113 publications

References 22 publications

Inositol monophosphatase activity from the Escherichia coli suhB gene product

Inositol monophosphatase activity from the Escherichia coli suhB gene product

Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited

β-Catenin Overexpression in the Mouse Brain Phenocopies Lithium-Sensitive Behaviors

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