Mevalonic acid
Introduction
Mevalonic acid (MVA) is a key organic compound in the biosynthesis of numerous biochemically significant molecules. It is a precursor to sterols, terpenes, and isoprenoids, which are vital components of all living cells. The compound is derived from acetyl-CoA in a process known as the mevalonate pathway, a crucial metabolic pathway present in eukaryotes, archaea, and some bacteria.
Structure and Properties
Mevalonic acid is a six-carbon compound with a carboxylic acid and a hydroxyl group. Its molecular formula is C6H12O4. The compound exists as white crystals at room temperature and is soluble in water. It has a melting point of 156-158 degrees Celsius. The structure of mevalonic acid is characterized by its three carbon backbone, which is derived from acetyl-CoA.
Biosynthesis
The biosynthesis of mevalonic acid is a crucial part of the mevalonate pathway. This process begins with the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA. The acetoacetyl-CoA is then reduced to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by the enzyme HMG-CoA reductase. The HMG-CoA is then converted to mevalonic acid by the same enzyme in a reaction that requires two molecules of NADPH.
Role in the Mevalonate Pathway
The mevalonate pathway is a crucial metabolic pathway that leads to the synthesis of several important classes of molecules. Mevalonic acid is a key intermediate in this pathway. Once synthesized, mevalonic acid is phosphorylated by mevalonate kinase to mevalonate-5-phosphate. This is then converted to mevalonate-5-diphosphate by phosphomevalonate kinase. Finally, the mevalonate-5-diphosphate is decarboxylated to isopentenyl-5-diphosphate, a key building block for the synthesis of sterols, terpenes, and isoprenoids.
Biological Significance
Mevalonic acid and its derivatives play a central role in the biology of all living organisms. The molecules synthesized from mevalonic acid, such as sterols, terpenes, and isoprenoids, are essential components of cell membranes, signaling molecules, and metabolic intermediates. In humans, the mevalonate pathway is also the target of certain cholesterol-lowering drugs, such as statins, which inhibit HMG-CoA reductase and thus reduce the synthesis of mevalonic acid.
Clinical Significance
The mevalonate pathway and mevalonic acid have significant clinical implications. The pathway is the target of several drugs, most notably the statins, which are used to lower cholesterol levels in patients with cardiovascular disease. These drugs inhibit HMG-CoA reductase, reducing the production of mevalonic acid and thus lowering the synthesis of cholesterol. Mutations in the genes encoding enzymes of the mevalonate pathway can lead to diseases such as mevalonate kinase deficiency, a rare genetic disorder characterized by recurrent fevers, developmental delay, and other symptoms.