Inositol oxygenase
myo-inositol oxygenase | |||||||
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Chr. 22 q | |||||||
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Inositol oxygenase, also commonly referred to as myo-inositol oxygenase (MIOX), is a non-
Structure
Myo-inositol oxygenase is a monomeric 33
The overall structure of the mouse MIOX is primarily helical with five
the MIOX protein fold diverges from that of other non-heme di-iron oxygenases including ribonucleotide reductase and soluble methane monooxygenase.[8] Instead, MIOX closely resembles proteins in the HD-domain superfamily based on its highly conserved metal binding strategy and the presence of the four His ligands on the iron center.[5]
Mechanism
MIOX can accept D- This binding step positions the myo-inositol prior to the catalytic steps which involve attack of an iron center by diatomic oxygen followed by abstraction of a myo-inositol hydrogen atom.
A superoxide Fe(III)/Fe(III) species is formed as diatomic oxygen displaces water as a coordinating ligand on one of the Fe atoms. Next, the hydrogen atom from C1 of
Biological Function
Myo-inositol can be ingested from fruits and vegetables and actively transported into cells or instead directly synthesized from glucose.[13] In the kidney, MIOX converts myo-inositol to glucuronic acid which is then able to enter the glucuronate-xylulose pathway for conversion to xylulose-5-phosphate.[13] This product can then easily enter the pentose phosphate pathway. Hence, MIOX enables the conversion and catabolism of inositol to generate NADPH and other pentose sugars.
Disease Relevance.
Myo-inositol is a component of the
There is also interest in evaluating MIOX expression as a potential biomarker of acute kidney injury. MIOX expression was shown to increase in the serum of animals and plasma of critically ill patients within 24 hours of acute kidney injury specifically.[16] An immunoassay of MIOX expression may potentially predict these life-threatening injuries earlier than the current diagnostic—detection of plasma creatinine.
Industrial Relevance
The MIOX enzyme has been the object of intense metabolic engineering efforts to produce glucaric acid through biosynthetic pathways. In 2004, the U.S. Department of Energy released a list of the top value-added chemicals from biomass which included glucaric acid—the direct product of the oxidation of glucuronic acid. The first biosynthetic production of glucaric acid was achieved in 2009 with use of the uronate dehydrogenase (UDH) enzyme.[17] Since then, the MIOX enzyme has been engineered for improved glucaric acid production through numerous strategies including appendage of an N-terminal SUMO-tag, directed evolution[18] and also the use of modular, synthetic scaffolds to increase its effective local concentration.
See also
- Inositol
- Glucuronic acid
- Oxygenases
References
External links
- Inositol+Oxygenase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)