Mevalonatweg
The mevalonate pathway is a metabolic pathway in eukaryotes via which the biosynthesis of isoprenoids takes place starting from acetyl-CoA and thus enables the formation of steroids and secondary metabolites . After six steps, the end product of the mevalonate pathway is isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), the starting materials in humans for cholesterol biosynthesis and steroid biosynthesis . Parts of the mevalonate pathway take place in the cytosol and in the peroxisomes .
Most bacteria use the methylerythritol phosphate pathway to synthesize isoprenoids , but the enzymes of the mevalonate pathway are also available to many. Archaea, on the other hand, only use the mevalonate pathway in a slightly different order, in which phosphomevalonate is first decarboxylated to isopentenyl phosphate and then further phosphorylated to IPP.
Reaction steps
Acetoacetyl-CoA
The mevalonate pathway begins in the mitochondria with the transfer of an acetyl residue from acetyl-CoA to a second acetyl-CoA molecule. This reaction equilibrium, catalyzed by the cytosolic enzyme acetyl-CoA-acetyltransferase (ACAT2), is also part of the beta-oxidation , the build-up and breakdown of keto bodies and some amino acids .
+ CoA-SH + 
Two molecules of acetyl-CoA are converted into coenzyme A and acetoacetyl-CoA and vice versa.
HMG-CoA
The linkage of another molecule of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) in the mitochondria requires the cytosolic isoform of the enzyme HMG-CoA synthase (HMGCS1).
+ + CoA-SH
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Acetoacetyl-CoA is acetylated to HMG-CoA.
R -Mevalonate
The HMG-CoA reductase is a membrane protein on the endoplasmic reticulum , the reduction of HMG-CoA to, mevalonate catalyzed. This step determines the speed of the mevalonate pathway, and thus also, for example, for the build-up of cholesterol.
+ 2 NADPH / H + + CoA-SH + 2 NADP + -Mevalonat.svg){kind=small}
HMG-CoA is reduced to mevalonate.
5- phospho - R mevalonate
The phosphorylation of mevalonate with the help of the mevalonate kinase takes place in the cytosol.
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R- evalonate is converted to 5-phospho- R -mevalonate. One molecule of ATP is used up.
5-diphospho- R mevalonate
Another phosphorylation leads to 5-pyrophosphomevalonate. The catalyst here is phosphomevalonate kinase , which has so far only been found in peroxisomes.
+ ATP + ADP -5-Pyrophosphomevalonat.svg){kind=small}
5-Phospho- R -mevalonate is converted to 5-Diphospho- R -mevalonate.
Isopentenyl pyrophosphate
The final reaction step for IPP provides the pyrophosphomevalonate decarboxylase catalyzed decarboxylation is of Diphosphomevalonat. It takes place in the cytosol.
+ ATP + ADP + P i + CO 2 
5-Diphospho- R mevalonate is converted to isopentenyl pyrophosphate (IPP).
Dimethylallyl diphosphate
The mutual isomerization of IPP to DMAPP and vice versa is catalyzed by isopentenyl diphosphate isomerase . Both isoforms of the enzyme were localized in peroxisomes.
Isopentenyl diphosphate (also called pyrophosphate) (IPP) and dimethylallyl diphosphate (also called pyrophosphate) (DMAPP) merge.
literature
- Qureshi N, Porter W: Conversion of acetyl-coenzyme A to isopentenyl pyrophosphate . In: JW Porter, SL Spurgeon (Ed.): Biosynthesis of Isoprenoid Compounds, Vol 1. John Wiley & Sons, New York, 1981, pp. 47-94 .
- McGarvey DJ, Croteau R: Terpenoid metabolism . In: Plant Cell . 7, No. 7, July 1995, pp. 1015-26. doi : 10.1105 / tpc.7.7.1015 . PMID 7640522 . PMC 160903 (free full text).
- Newman JD, Chappell J: Isoprenoid biosynthesis in plants: carbon partitioning within the cytoplasmic pathway . In: Crit. Rev. Biochem. Mol. Biol . 34, No. 2, 1999, pp. 95-106. doi : 10.1080 / 10409239991209228 . PMID 10333387 .
Individual evidence
- ↑ MetaCyc: mevalonate pathway I
- ↑ MetaCyc: mevalonate pathway (archaea) II
