A cascata dos fosfoinositídeos

Abstract

Recebido em 30/1/02; aceito em 24/6/02 THE PHOSPHOINOSITIDE CASCATE. Inositol is a polyalcohol required for the proper formation of cell membranes. In the body, its plays an important role in the transmission of nerve impulses, its also helps in the transporting of fats within the body. In mammals, inositol exists as phosphorylated derivatives, various phosphoinositides, and in its free form. Agonist stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] is the first step in the transmembrane signalling mechanism when cells respond to external stimuli. Under control of activated phospholipase C (PLC) via G-protein, two second messengers Dmyo-inositol 1,4,5-triphosphate [Ins(1,4,5)P 3 ] and diacylglycerol are released into the cell. From Ins(1,4,5)P 3 , enzymatic process under phosphatases or kinases control affords subsequent inositol phosphate metabolites. During the last decade the synthesis of modified inositol phosphate derivatives has been strongly investigated. This paper reviews principal aspects about synthesis and biological functions of these biomolecules.Keywords: second messengers; phosphoinositides; inositol phosphate. INTRODUÇÃO À QUÍMICA DOS INOSITÓISO inositol é um poliálcool cíclico contendo um anel de seis áto-mos de carbono e seis grupos OH (cicloexanopoliol), sendo um importante constituinte celular, estando envolvido em diferentes processos bioquímicos. Em mamíferos o inositol existe principalmente sob a forma de derivados fosforilados, os quais participam da comunicação celular. Nomenclatura dos inositóisOs inositóis podem ser arranjados em nove estereoisômeros: scilo, mio, neo, epi, D e L quiro, cis, muco e allo (Figura 1).Entre os isômeros mostrados na Figura 1, o mio-inositol é o mais abundante na natureza, sendo produzido a partir da glicose. De acordo com a nomenclatura oficial, o único grupo hidroxila axial do mioinositol (I) ocupa a posição C-2 na estrutura (Figura 2). A fosforilação em O-1 do mio-inositol leva ao 1L-mio-inositol 1-fosfato (II), no entanto, a fosforilação na posição O-3, altera a numeração dos áto-mos de carbono, invertendo C-1 com C-3, levando ao 1D-mio-inositol 1-fosfato (III).O mio-inositol é um composto meso, visto que apresenta um plano de simetria passando pelos átomos C-2 e C-5 (Figura 2). Toda mono-substituição nas posições 1, 3, 4 ou 6 gera, portanto, um racemato. O símbolo InsO símbolo Ins é utilizado para o mio-inositol com configuração 1D. Caso seja de configuração L, esta deve ser previamente mencionada. A terminação P x , em itálico, indica o número de fosforilações presentes no inositol. Figura 1. Estereoisômeros do inositolFigura 2. Nomenclatura e plano de simetria do mio-inositol

Molecular modeling as a promising tool to study dendrimer prodrugs delivery

“…Myo-inositol is a polyalcohol and, for this reason, fulfills the requirements of a core to the dendrimer growth. Moreover, it is an important cellular constituent involved in different biochemical pathways which could result in low immunogenicity [20].…”

Aqueous ethanol extract of Libidibia ferrea (Mart. Ex Tul) L.P. Queiroz (juca) exhibits antioxidant and migration-inhibiting activity in human gastric adenocarcinoma (ACP02) cells

“…Notably, the extracellular microenvironment has been shown to modulate the organization and expression of the filaments that form the cytoskeleton [43]. The juca AE extract was found to contain myo-inositol, which is involved in cytoskeletal assembly/disassembly and the cell adhesion that is important for cell locomotion [46]. We therefore speculate that the addition of other compounds, constituent of juca AE extract, such as myo-inositol (unrelated to its antioxidant potential) to the extracellular medium can alter the organization and/or polymerization/ depolymerization of the cytoskeleton, and thus prevent cell migration.…”

The effects of an osmoregulator, carbohydrates and polyol on maturation and germination of ‘Golden THB’ papaya somatic embryos

“…Among the different MI concentrations in the germination medium, 0.45 mM resulted in significant gains in the germination percentage of 'Golden THB' papaya somatic embryos (47.42%), an increase of 11.19%, while the medium lacking MI provided 36.23% germination (Figure 4). MI is a cyclic polyalcohol, an important cellular constituent involved in different biochemical processes (Almeida et al 2003). In plants, MI is a precursor of several metabolites, leading to the production of phytic acid via the sequential phosphorylation of myo-inositol by myo-inositol-3-phosphate synthase (MIPS) (Abreu and Aragão 2007).…”