Inositol Metabolism
Carbohydrate Metabolism

Author: Gianpiero Pescarmona
Date: 18/01/2008


Inositol, (of which the most prominent naturally-occurring form is myo-inositol, cis-1,2,3,5-trans-4,6-cyclohexanehexol), is a carbocyclic polyol that plays an important role as the structural basis for a number of secondary messengers in eukaryotic cells (Kegg Pathways)

Inositol endogenous synthesis (Kegg Pathways)

Myo-Inositol is synthesized from glucose-6-phosphate (G-6-P) in two steps. First, G-6-P is isomerised by INYNA1 to myo-inositol 1-phosphate, which is then dephosphorylated by IMPA1 to give myo-inositol.

The synthesis of inositol requires oxidized nicotinamide adenine dinucleotide (NAD) and was stimulated by NH4C1 and MgC12. NADH inhibits the reaction. Phosphorylated inositol accumulated in the absence of MgC12, suggesting that inositol-phosphate is an intermediate in the pathway and that Mg ions stimulate the dephosphorylation of inositol-phosphate.

The limiting step in the Inositol synthesis is INYNA1 (INO1_HUMAN) that has a *GLU/GLN = 1.66

Inositol uptake from the diet

Uptake is a Na+-dependent process and it is inhibited by high glucose (20 mM).

myo-Inositol Phosphates synthesis

inositol phosphates during cell cycle 2007


The proapoptotic factors Bax and Bak regulate T Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis.


Myo-inositol to chiro-inositol conversion

myo-Inositol oxygenase (MIOX) catalyses the first committed step in the only pathway of myo-inositol catabolism, which occurs predominantly in the kidney . The enzyme is a non-haem-iron enzyme that catalyses the ring cleavage of myo-inositol with the incorporation of a single atom of oxygen.

Myo-Inositol oxygenase: molecular cloning and expression of a unique enzyme that oxidizes myo-inositol and D-chiro-inositol, 2001

Risk factors for hepatic encephalopathy in patients with cirrhosis and refractory ascites: relevance of serum sodium concentration. 2010

  • Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo-osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large-volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow-up and at the time of development of HE in patients who developed this complication. During a mean follow-up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia.

Subclinical hepatic encephalopathy: proton MR spectroscopic abnormalities. 1994

MATERIALS AND METHODS In a double-blind study, overt hepatic encephalopathy (HE) and SCHE (defined with clinical and neuropsychiatric tests) were compared by means of H-1 MR spectroscopic criteria--reduction in cerebral myo-inositol (< 2 standard deviations [SDs] from normal) and choline (< 2 SDs from normal) with or without increased cerebral glutamine (> 1 SD from normal)--in 20 patients with cirrhosis.

Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging. 1997

Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16).

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