2-C-Methylerythritol 4-phosphate

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2-C-Methylerythritol 4-phosphate (MEP) is a critical intermediate in the non-mevalonate pathway (also known as the MEP/DOXP pathway) of isoprenoid biosynthesis. This pathway is responsible for the production of essential isoprenoids in most bacteria, algae, and plants, but is absent in animals, making it an interesting target for the development of antibiotics, herbicides, and antimalarial drugs.

Biosynthesis[edit | edit source]

The MEP pathway begins with the condensation of pyruvate and glyceraldehyde 3-phosphate (G3P) to produce 1-deoxy-D-xylulose 5-phosphate (DXP). Through a series of enzymatic reactions, DXP is then converted to 2-C-methylerythritol 4-phosphate. The enzyme IspE catalyzes the conversion of MEP to 4-diphosphocytidyl-2-C-methyl-D-erythritol, a further step in the pathway leading to the production of isoprenoids.

Function[edit | edit source]

Isoprenoids, the products of the MEP pathway, are a large and diverse group of molecules that play crucial roles in various biological processes. They are involved in the synthesis of chlorophylls, carotenoids, plant hormones, and quinones. In bacteria, isoprenoids are essential for the synthesis of cell membrane constituents and electron transport chain components.

Clinical Significance[edit | edit source]

Due to its absence in humans, the MEP pathway is an attractive target for the development of new antimicrobial and antiparasitic agents. Inhibitors of the MEP pathway enzymes have shown potential as antibiotics against a range of bacteria and as antimalarial agents. For example, fosmidomycin, an inhibitor of the enzyme DOXP reductoisomerase (which acts early in the MEP pathway), has shown efficacy against Plasmodium falciparum, the parasite responsible for malaria.

Research[edit | edit source]

Research into the MEP pathway and its inhibitors is ongoing, with the aim of developing new therapeutic agents. Understanding the structure and function of the enzymes involved in the MEP pathway is crucial for the design of effective inhibitors.

See Also[edit | edit source]

External Links[edit | edit source]

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Contributors: Prab R. Tumpati, MD