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Inositol monophosphatase is a phosphodiesterase enzyme that is often called IMPase.
It works in the PI (phosphatidylinositol) pathway of signaling and accommodates a variety of vital cellular functions including apoptosis, growth and repair, processing information and secreting.
Inositol monophosphatase is most noted for its key role in lithium action, a main pharmaceutical treatment for bipolar disorder and manic depression.
Every subunit of this dimer enzyme is made up of the residue of 277 amino acids. Each separate dimer component comprises five layers of beta-sheets alternating with alpha-helices.
Each subunit has 9 alpha-helices and beta-sheets. There are three active binding sites which remain hollow on IMPase molecules. These hollow sites attract and accept magnesium and water molecules.
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Top Inositol Products* ❯The Phosphorylation Process
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Inositol phosphates play several roles in the brain and body.
The addition of a phosphate group to any organic compound is called phosphorylation. This process activates and deactivates various protein-based enzymes.
This causes an array of cellular functioning and activities. When a protein is phosphorylated, it is known as a type of post-translational modification, the effects of which have been explored in more than 200,000 research articles.
Protein phosphorylation is responsible for numerous critical cellular functions. In fact, it is the most prevalent mechanism that regulates the functions of proteins. It controls the neuron signaling transmissions inside of eukaryotic cells.
Inositol plays an integral role in accommodating efficient transduction signaling. Researchers say that many proteins known in the human proteome are used as substrates for the processes of phosphorylation and reverse phosphorylation.
Phosphoproteomics is a subdiscipline of proteomics that focuses solely on identifying phosphorylated proteins.
Clinical Significance of Inositol Monophosphatase
Mainstream mood stabilizing pharmaceuticals still have undefined molecular action sites. It is unclear how they act to enhance mood and prevent symptoms of these disorders, if and when they are effective at all.
Myo-inositol monophosphatase, being a very effective enzyme of the inositol signaling system, has been clinically proven to be inhibited by therapeutic doses of Li+ (lithium). This implies that IMPase is a likely action site for manic-depressive disorder therapy.
What this means is that when IMPase is inhibited, myo-inositol monophosphates are not efficiently converted to myo-inositol any longer. This results in lowered levels of myo-inositol and elevated levels of myo-inositol phosphates.
The lessened bioavailability of myo-inositol hinders the resynthesis of inositol-based phospholipids. The likelihood that IMPase activity is responsible for the positive effects of lithium and other mood stabilizers is a catalyst for continuously ongoing clinical research.
Lithium Therapy for Bipolar Disorder
For decades, lithium was considered the best of very few treatments for bipolar disorder.
In 1817, lithium was discovered. By the later part of the 1800s, it was noted that lithium seemed to have certain positive effects on mood disorders. This occurred coincidentally when physicians of the day were experimenting with lithium as a treatment for the symptoms of gout.
It was in 1949 that Australian psychiatrist John Cade published the first work proclaiming the effectiveness of lithium as a treatment for symptoms associated with acute mania. Twenty-one years later, the US FDA approved lithium for general societal use.
Lithium was first used to treat mental conditions because it was noted to positively affect patients with mood disorders. It has never been clinically proven that there is any correlation between lacking lithium and the onset of bipolar disorder.
It was preferable to patients that other treatments of the time because lithium occurs naturally and it seemed to help. Lithium soon became the preferred treatment for bipolar disorder. Still, there was a lack of information regarding how or why it worked when it did.
Inositol Monophosphatase and Lithium
In 1998, the University of Wisconsin finally uncovered the fact that lithium works by affecting the performance of inner brain neurons. Additionally, lithium has strong effects on the glutamate neurons, an important excitatory neurotransmitter.
Lithium keeps the amount of glutamate in the synaptic clefts at balanced levels. This is very important because a surplus of glutamate in synaptic clefts can cause epileptic seizures and excitotoxicity to occur. Lithium is also noted for its capacity to possibly prevent cellular necrosis from occurring in key brain areas that may dictate the onset of Parkinson’s, Alzheimer’s and Huntington’s diseases.
The concern with lithium is that its therapeutic doses are potentially unsafe. Lithium is a toxic metallic substance. Although it has been somewhat successful over the decades as a treatment for bipolar disorder, its toxicity rates make it undesirable to many.
That being so, a new substance that could inhibit IMPase without the potential for toxicity, as with lithium, is being sought on a worldwide level.
Understanding the many important biological and psychological roles of inositol and inositol phosphates like inositol monophosphatase is imperative for developing safer, more effective treatments for debilitating conditions like bipolar disorder. The potential benefits of the inositol phosphate group continues to be explored by leading research groups in every advanced country.
Article last updated on: May 12th, 2018 by Nootriment