The determination of inositol in animal tissues

Young, L.

doi:10.1042/bj0281435

Cited by 11 publications

(2 citation statements)

References 5 publications

(5 reference statements)

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“…A special function for inositol in the nervous system was first suggested by the discovery of a relatively high inositol content in the brains of many species (Young 1934; Long 1961). Folch found that cephalin contained lipid‐bound inositol (Folch and Woolley 1942), which was eventually shown to be one of three phosphoinositides: phosphatidylinositol (PI), phosphatidylinositol‐4‐phosphate (PI4P) and phosphatidylinositol‐4,5‐bisphosphate [PI(4,5)P 2 ].…”

Section: Historical Overviewmentioning

confidence: 99%

Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Fisher

Novak

Agranoff

2002

Journal of Neurochemistry

353

306

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Inositol phospholipids and inositol phosphates mediate wellestablished functions in signal transduction and in Ca 2+ homeostasis in the CNS and non-neural tissues. More recently, there has been renewed interest in other roles that both myo-inositol and its highly phosphorylated forms may play in neural function. We review evidence that myo-inositol serves as a clinically relevant osmolyte in the CNS, and that its hexakisphosphate and pyrophosphorylated derivatives may play roles in such diverse cellular functions as DNA repair, nuclear RNA export and synaptic membrane trafficking.

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Section: Historical Overviewmentioning

confidence: 99%

Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Fisher

Novak

Agranoff

2002

Journal of Neurochemistry

353

306

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“…myo -Inositol (MI) is the most abundant of the nine stereoisomers of cyclohexanehexol, − and relatively high concentrations are present in the central nervous system (CNS) . MI is a precursor of phosphatidylinositol (PtdIns) as well as its mono-, di-, and triphosphates (PtdInsP or phosphoinositides) that play pivotal roles in PtdIns signaling and mediate a range of other essential cellular processes. − MI also forms the structural backbone of inositol phosphates (InsP) and their pyrophosphate derivatives; the prominent roles of InsP and derivatives in signal transduction and as cell controllers have been well documented. ,− For example, the extensively studied inositol 1,4,5-triphosphate (Ins(1,4,5)P 3 ) induces the release of intracellular calcium. − Given that MI is involved in a number of signaling processes and that changes in its level may alter the concentration of many other inositol derivatives, it can be predicted that, without strict maintenance of the MI level, many intracellular processes will be altered, which might then trigger CNS pathology.…”

Section: Introductionmentioning

confidence: 99%

ONIOM (DFT:MM) Study of the Catalytic Mechanism of myo-Inositol Monophosphatase: Essential Role of Water in Enzyme Catalysis in the Two-Metal Mechanism

Wang

Hirao

2013

J. Phys. Chem. B

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myo-Inositol monophosphatase (IMPase), a putative target of lithium therapy for bipolar disorder, is an enzyme that catalyzes the hydrolysis of myo-inositol-1-phosphate (Ins(1)P) into myo-inositol (MI) and inorganic phosphate. It is known that either two or three Mg(2+) ions are used as cofactors in IMPase catalysis; however, the detailed catalytic mechanism and the specific number of Mg(2+) ions required have long remained obscure. To obtain a clearer view of the IMPase reaction, we undertook extensive ONIOM hybrid quantum mechanics and molecular mechanics (QM/MM) calculations, to evaluate the reaction with either three or two Mg(2+) ions. Our calculations show that the three-metal mechanism is energetically unfavorable; the initial inline attack of a hydroxide ion on the Ins(1)P substrate markedly destabilized the system without producing any stable transition state or intermediate. By contrast, for the two-metal mechanism, a favorable pathway was obtained from QM/MM calculations. In our proposed two-metal mechanism, the phosphoryl oxygen of the substrate acts as an acid-base catalyst, activating a water molecule in the first step, and the resultant hydroxide ion attacks the substrate in an inline fashion. A second water molecule, bound to a Mg(2+) ion, was found to play an essential role in the final proton-transfer step that leads to the formation of an MI product; this is achieved by lowering the energy barrier by 2.5 kcal/mol compared with the barrier for the mechanism that does not use this water molecule. Our results should advance our understanding of the IMPase mechanism, and this could have profound implications for the treatment of disease in the central nervous system.

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Inositol in the Ocular Tissues

Krause¹,

Weekers²

1938

Archives of Ophthalmology

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The determination of inositol in animal tissues

Abstract: MANY attempts have been made to devise a satisfactory method of determining the inositol content of animal tissues. The nature of inositol and the absence of a simple method of estimating the substance have both contributed to the

Cited by 11 publications

References 5 publications

Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance

ONIOM (DFT:MM) Study of the Catalytic Mechanism of myo-Inositol Monophosphatase: Essential Role of Water in Enzyme Catalysis in the Two-Metal Mechanism

Inositol in the Ocular Tissues

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