Phosphomevalonic acid: Difference between revisions

Latest revision as of 06:19, 16 February 2025

Overview[edit]

Phosphomevalonic acid is an important intermediate in the mevalonate pathway, a crucial metabolic pathway that leads to the biosynthesis of isoprenoids and sterols, including cholesterol. This pathway is essential in all higher eukaryotes and many prokaryotes.

Structure and Function[edit]

Phosphomevalonic acid, also known as mevalonate-5-phosphate, is a phosphorylated derivative of mevalonic acid. It is formed by the action of the enzyme mevalonate kinase, which catalyzes the phosphorylation of mevalonic acid using ATP as a phosphate donor.

The chemical structure of phosphomevalonic acid includes a six-carbon backbone with a phosphate group attached to the fifth carbon. This modification is critical for its role in the subsequent steps of the mevalonate pathway.

Role in the Mevalonate Pathway[edit]

In the mevalonate pathway, phosphomevalonic acid is further phosphorylated by the enzyme phosphomevalonate kinase to form mevalonate-5-diphosphate. This step is crucial for the eventual production of isopentenyl pyrophosphate (IPP), the building block for the synthesis of all isoprenoids.

The pathway proceeds as follows:

Mevalonic acid is phosphorylated by mevalonate kinase to form phosphomevalonic acid.
Phosphomevalonic acid is then phosphorylated by phosphomevalonate kinase to form mevalonate-5-diphosphate.
Mevalonate-5-diphosphate is decarboxylated to form isopentenyl pyrophosphate (IPP).

Biological Significance[edit]

The mevalonate pathway, and by extension phosphomevalonic acid, is vital for the production of several key biological molecules. These include:

Cholesterol, which is a fundamental component of cell membranes and a precursor for steroid hormones.
Ubiquinone (coenzyme Q), which is essential for the electron transport chain in mitochondria.
Dolichol, which is involved in the glycosylation of proteins.

Clinical Relevance[edit]

Disruptions in the mevalonate pathway can lead to various metabolic disorders. For example, deficiencies in mevalonate kinase can result in mevalonate kinase deficiency, a rare genetic disorder that can cause developmental delays and immune system dysfunction.

Additionally, the mevalonate pathway is the target of statins, a class of drugs used to lower cholesterol levels in patients with hypercholesterolemia. Statins inhibit HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step of the pathway.

Related Pages[edit]

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-Phosphomevalonic acid is a crucial intermediate in the biosynthesis of isoprenoids, which are essential compounds involved in various biological processes. It is formed through the condensation of acetyl-CoA and acetoacetyl-CoA by the enzyme HMG-CoA synthase. Phosphomevalonic acid plays a key role in the mevalonate pathway, a metabolic pathway responsible for the production of isoprenoids such as cholesterol, steroid hormones, and dolichols.
+{{DISPLAYTITLE:Phosphomevalonic acid}}
+== Overview ==
+[[File:Mevalonate_pathway.png|thumb|right|Diagram of the mevalonate pathway, showing the role of phosphomevalonic acid.]]
+'''Phosphomevalonic acid''' is an important intermediate in the [[mevalonate pathway]], a crucial metabolic pathway that leads to the biosynthesis of [[isoprenoids]] and [[sterols]], including [[cholesterol]]. This pathway is essential in all higher eukaryotes and many prokaryotes.
 == Structure and Function ==
-Phosphomevalonic acid is a phosphorylated derivative of mevalonic acid, which is a key precursor in the biosynthesis of isoprenoids. The phosphorylation of mevalonic acid is catalyzed by the enzyme mevalonate kinase, leading to the formation of phosphomevalonic acid. This phosphorylation step is essential for the subsequent conversion of phosphomevalonic acid into isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are the building blocks for the synthesis of various isoprenoid compounds.
+Phosphomevalonic acid, also known as mevalonate-5-phosphate, is a phosphorylated derivative of [[mevalonic acid]]. It is formed by the action of the enzyme [[mevalonate kinase]], which catalyzes the phosphorylation of mevalonic acid using [[ATP]] as a phosphate donor.
+The chemical structure of phosphomevalonic acid includes a six-carbon backbone with a phosphate group attached to the fifth carbon. This modification is critical for its role in the subsequent steps of the mevalonate pathway.
+== Role in the Mevalonate Pathway ==
+In the [[mevalonate pathway]], phosphomevalonic acid is further phosphorylated by the enzyme [[phosphomevalonate kinase]] to form [[mevalonate-5-diphosphate]]. This step is crucial for the eventual production of [[isopentenyl pyrophosphate]] (IPP), the building block for the synthesis of all isoprenoids.
+The pathway proceeds as follows:
+# Mevalonic acid is phosphorylated by mevalonate kinase to form phosphomevalonic acid.
+# Phosphomevalonic acid is then phosphorylated by phosphomevalonate kinase to form mevalonate-5-diphosphate.
+# Mevalonate-5-diphosphate is decarboxylated to form isopentenyl pyrophosphate (IPP).
+== Biological Significance ==
+The mevalonate pathway, and by extension phosphomevalonic acid, is vital for the production of several key biological molecules. These include:
+* [[Cholesterol]], which is a fundamental component of cell membranes and a precursor for steroid hormones.
+* [[Ubiquinone]] (coenzyme Q), which is essential for the electron transport chain in [[mitochondria]].
+* [[Dolichol]], which is involved in the glycosylation of proteins.
-== Role in Isoprenoid Biosynthesis ==
+== Clinical Relevance ==
-Phosphomevalonic acid serves as a critical intermediate in the mevalonate pathway, which is the primary pathway for the biosynthesis of isoprenoids in most organisms. Isoprenoids are a diverse class of compounds that play essential roles in cellular functions, including membrane structure, signaling molecules, and electron carriers. The conversion of phosphomevalonic acid into IPP and DMAPP is a key regulatory step in the mevalonate pathway and is tightly controlled to ensure the production of isoprenoids in the appropriate quantities for cellular needs.
+Disruptions in the mevalonate pathway can lead to various metabolic disorders. For example, deficiencies in mevalonate kinase can result in [[mevalonate kinase deficiency]], a rare genetic disorder that can cause developmental delays and immune system dysfunction.
-== Clinical Significance ==
+Additionally, the mevalonate pathway is the target of [[statins]], a class of drugs used to lower cholesterol levels in patients with hypercholesterolemia. Statins inhibit [[HMG-CoA reductase]], the enzyme that catalyzes the rate-limiting step of the pathway.
-Dysregulation of the mevalonate pathway, including the metabolism of phosphomevalonic acid, has been implicated in various human diseases. Mutations in genes encoding enzymes involved in the mevalonate pathway can lead to metabolic disorders characterized by the accumulation of toxic intermediates or the deficiency of essential isoprenoid products. For example, deficiencies in mevalonate kinase, the enzyme responsible for the phosphorylation of mevalonic acid to form phosphomevalonic acid, can result in mevalonic aciduria, a rare autosomal recessive disorder with symptoms including developmental delay, intellectual disability, and recurrent fevers.
-== References ==
+== Related Pages ==
-* [[Mevalonic acid]]
-* [[Isoprenoid biosynthesis]]
 * [[Mevalonate pathway]]
+* [[Cholesterol]]
+* [[Isoprenoids]]
+* [[Statins]]
 [[Category:Biochemistry]]
 [[Category:Metabolic pathways]]
-{{medicine-stub}}