Stereochemistry of the myo-inositol-1-phosphate synthase reaction.

Loewus, Mary W.; Loewus, Frank A.; Brillinger, G. U.; Otsuka, Hideaki; Floss, Heinz G.

doi:10.1016/s0021-9258(19)70191-4

Cited by 75 publications

(37 citation statements)

References 18 publications

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“…MI derives from the isomerization of glucose-6-phosphate (G6P) to inositol-3-phosphate (Ins3P) by the enzyme D-3-myo-inositol-phosphate synthase (inositol synthase, Ino1 or MIPS1) [9]. Then, inositol-3-phosphate is dephosphorylated to free MI by means of inositol-monophosphatase-1 (IMPA-1 or IMPase) [10]. Free MI can also be generated by the recycling of inositol-1,4,5-trisphosphate (InsP3) and inositol-1,4-bisphosphate (InsP2) generated in inositol phosphate signaling [11].…”

Section: Biochemical Propertiesmentioning

confidence: 99%

An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

Facchinetti

Cavalli

Copp

et al. 2020

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). Areas covered: In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. Expert opinion: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.

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Section: Biochemical Propertiesmentioning

confidence: 99%

An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

Facchinetti

Cavalli

Copp

et al. 2020

Expert Opinion on Drug Metabolism & Toxicology

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“…Inositol-containing molecules are critical players of many cellular processes in addition to aminoglycoside antibiotic production and are involved in signal transduction pathways, stress response, and cell wall biogenesis. 10-12 myo-Inositol 1-phosphate (MIP) synthase performs the first step in the synthesis of all inositol-derived compounds, the conversion of glucose 6-phosphate (15) to MIP (18), and has been reported from both prokaryotic and eukaryotic sources. 13 Primary sequence analysis reveals that MIP synthases of prokaryotic origin comprise a very diverse set of enzymes that are distinct from their eukaryotic counterparts.…”

Section: The Origin Of Myo-inositol 1-phosphatementioning

confidence: 99%

“…14 In spite of this striking diversity, it appears that the core three dimensional structure and overall reaction mechanism of MIP synthases are well conserved. [15][16][17][18] Furthermore, the reaction represents the first committed step in inositol biosynthesis and can act as a ratelimiting step in the synthesis of aminoglycoside antibiotics. Thus, the biochemical activity and reaction mechanism of MIP synthase is of considerable interest.…”

Section: The Origin Of Myo-inositol 1-phosphatementioning

confidence: 99%

“…The reaction mechanism of MIP synthase is proposed to involve three distinct steps, including an oxidation, an intramolecular aldol cyclization and a reduction (Scheme 1). 13, 15 Crystallographic data indicate that MIP synthase utilizes two cofactors, NAD + and the monovalent cation, NH 4 + . 16,18 Other classes of enzymes containing NAD + and a cation cofactor include dehydroquinate (DHQ) synthases and alcohol dehydrogenases.…”

Section: The Origin Of Myo-inositol 1-phosphatementioning

confidence: 99%

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Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds

Flatt,

Mahmud

2007

Nat. Prod. Rep.

124

120

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“…Endogenously, myo-Ins is synthetized from glucose-6-phosphate (G6P), which is isomerized to inositol-3-phosphate (InsP3) by D-3-myo-inositol-phosphate synthase enzyme (inositol synthase, Ino1, or MIPS1) [ 12 ]. Then, through inositol monophosphatase-1 (IMPA-1 or IMPase), InsP3 is dephosphorylated into free myo-Ins [ 13 ]. Free myo-Ins could also be obtained through dephosphorylation of inositol-1,4,5-trisphosphate (InsP3) and inositol-1,4-bisphosphate (InsP2).…”

Section: Introduction: An Overview On Inositolsmentioning

confidence: 99%

Inositols: From Established Knowledge to Novel Approaches

Dinicola¹,

Unfer²,

Facchinetti

et al. 2021

IJMS

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Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

show abstract

Stereochemistry of the myo-inositol-1-phosphate synthase reaction.

Cited by 75 publications

References 18 publications

An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs)

Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds

Inositols: From Established Knowledge to Novel Approaches

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