Non-mevalonate pathway

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Non-mevalonate pathway

DOXP

MEP

4-diphosphocytidyl-2-C-methylerythritol

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4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate

2-C-Methyl-D-erythritol-2,4-cyclopyrophosphate

Non-mevalonate pathway

The non-mevalonate pathway, also known as the methylerythritol phosphate (MEP) pathway, is an alternative metabolic pathway for the biosynthesis of isoprenoids. This pathway is distinct from the mevalonate pathway and is found in many bacteria, algae, and plants.

Overview

The non-mevalonate pathway is responsible for the production of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are essential precursors for the synthesis of various isoprenoids. Isoprenoids are a diverse class of organic compounds that play crucial roles in various biological processes, including photosynthesis, respiration, and cell membrane integrity.

Steps of the Non-mevalonate Pathway

The non-mevalonate pathway consists of several enzymatic steps:

1. 1-Deoxy-D-xylulose-5-phosphate (DXP) synthesis: The pathway begins with the condensation of pyruvate and glyceraldehyde 3-phosphate to form DXP, catalyzed by the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS).
2. 1-Deoxy-D-xylulose-5-phosphate (DXP) reduction: DXP is then reduced to 2-C-methyl-D-erythritol 4-phosphate (MEP) by the enzyme 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR).
3. MEP conversion to 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME): MEP is converted to CDP-ME by the enzyme 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD).
4. CDP-ME phosphorylation: CDP-ME is phosphorylated to 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) by the enzyme 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase (IspE).
5. CDP-ME2P conversion to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP): CDP-ME2P is converted to MEcPP by the enzyme 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF).
6. MEcPP conversion to (E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate (HMB-PP): MEcPP is converted to HMB-PP by the enzyme 4-hydroxy-3-methylbut-2-enyl pyrophosphate synthase (IspG).
7. HMB-PP reduction to IPP and DMAPP: Finally, HMB-PP is reduced to IPP and DMAPP by the enzyme 4-hydroxy-3-methylbut-2-enyl pyrophosphate reductase (IspH).

Biological Significance

The non-mevalonate pathway is essential for the survival of many pathogenic bacteria and parasites, making it a target for the development of new antibiotics and antimalarial drugs. Unlike the mevalonate pathway, which is present in animals, fungi, and some bacteria, the non-mevalonate pathway is absent in humans, providing a selective target for drug development.

Related Pages

• Isoprenoid
• Mevalonate pathway
• Photosynthesis
• Respiration
• Cell membrane
• Antibiotics
• Antimalarial drugs