The glycerophosphoinositols: cellular metabolism and biological functions

Abstract

The glycerophosphoinositols are cellular products of phospholipase A(2) and lysolipase activities on the membrane phosphoinositides. Their intracellular concentrations can vary upon oncogenic transformation, cell differentiation and hormonal stimulation. Specific glycerophosphodiester phosphodiesterases are involved in their catabolism, which, as with their formation, is under hormonal regulation. With their mechanisms of action including modulation of adenylyl cyclase, intracellular calcium levels, and Rho-GTPases, the glycerophosphoinositols have diverse effects in multiple cell types: induction of cell proliferation in thyroid cells; modulation of actin cytoskeleton organisation in fibroblasts; and reduction of the invasive potential of tumour cell lines. More recent investigations include their effects in inflammatory and immune responses. Indeed, the glycerophosphoinositols enhance cytokine-dependent chemotaxis in T-lymphocytes induced by SDF-1alpha-receptor activation, indicating roles for these compounds as modulators of T-cell signalling and T-cell responses.

New Members of the Mammalian Glycerophosphodiester Phosphodiesterase Family

“…Glycerophosphodiesters (GPs), 3 such as glycerophosphocholine (GroPCho), glycerophosphoinositol (GroPIns), glycerophosphoserine (GroPSer), and glycerophosphoethanolamine (GroPEth), are water-soluble metabolites of the glycerophospholipids. GPs are produced via phospholipase A 1 and phospholipase A 2 activities, and they are degraded by GP phosphodiesterases (GP-PDEs) (1)(2)(3)(4).…”

“…GPs are produced via phospholipase A 1 and phospholipase A 2 activities, and they are degraded by GP phosphodiesterases (GP-PDEs) (1)(2)(3)(4). Six mammalian GP-PDEs were previously isolated, and investigations have been carried out to explore their physiological significance (5,6).…”

A Novel Glycerophosphodiester Phosphodiesterase, GDE5, Controls Skeletal Muscle Development via a Non-enzymatic Mechanism

“…GP intracellular concentrations vary with oncogenic transformation, cell differentiation, and environmental stimuli, and they are thought to be tightly controlled for the balance between synthesis and degradation (7)(8)(9). For GP hydrolysis, two bacterial enzymes have been isolated and studied in depth at the molecular level.…”

“…In addition, our recent study demonstrates that GDE3 is a GroPIns phosphodiesterase that hydrolyzes GroPIns to glycerol and inositol 1-phosphate, unlike the bacterial GP-PDEs and GDE1 (18). In mammalian cells, GroPIns is being increasingly recognized as an important intracellular messenger that is involved in various cellular signaling pathways such as cell proliferation, transformation, and differentiation (9,18,19). Although these observations strongly suggest a central role of mammalian GP-PDEs in regulating intracellular GP concentrations, previous reports on the existence of proteins that interact with mammalian GP-PDEs, such as RGS16, PRAF2 (also known as JM4), and Prdx1 (12,20,21), have prompted us to consider that GP-PDEs might also act via a non-enzymatic mechanism.…”

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

“…These phospholipases are also known to be stimulated by heat shock (HS) and chemical stressors [57,58]. The lipid most affected by PUFA removal was PI (38:4), which can be metabolised mainly by PIspecific PLA 2 [59] or by PLC. The latter also hydrolyses PIP 2 , thereby producing two second messengers, diacylglycerol (DAG) and inositol triphosphate (IP 3 ) [60].…”