Mevalonate pathway

The mevalonate pathway is a pathway in eukaryotes, on the basis of acetyl-CoA occurs biosynthesis of isoprenoids and thus the structure of steroids and secondary metabolites is possible. End product of the mevalonate pathway is six steps isopentenyl pyrophosphate (IPP ) and dimethylallyl pyrophosphate ( DMAPP ), the starting materials used in humans for the biosynthesis of cholesterol and steroid biosynthesis. Parts of the mevalonate pathway take place in the cytosol, and peroxisomes.

Most bacteria use for the synthesis of isoprenoids the Methylerythritolphosphatweg, but many are also the enzymes of the mevalonate pathway are available. Archaea, however, only use the mevalonate pathway in a slightly different order, in phosphomevalonate first decarboxylated to Isopentenylphosphat and is then further phosphorylated to the IPP.

Reaction steps

Acetoacetyl -CoA

The mevalonate pathway in the mitochondria begin with the transmission of the acetyl from acetyl CoA to acetyl-CoA, a second molecule. This from the cytosolic enzyme acetyl -CoA acetyltransferase ( ACAT2 ) catalyzed reaction equilibrium is also part of the beta- oxidation, the assembly and disassembly of ketone bodies and some amino acids.

CoA -SH

Two molecules of acetyl CoA are reacted to form coenzyme A and acetoacetyl-CoA, and vice versa.

HMG -CoA

The linking of a further molecule of acetyl-CoA to acetoacetyl- CoA to 3-hydroxy -3-methylglutaryl -CoA ( HMG-CoA) in the mitochondria required for the cytosolic isoform of the enzyme HMG-CoA synthase ( HMGCS1 ).

CoA -SH

Acetoacetyl -CoA is acetylated to HMG-CoA.

R- mevalonate

The HMG -CoA reductase is a membrane protein on the endoplasmic reticulum, catalyzes the reduction of HMG-CoA to mevalonate. This step is rate-limiting for the mevalonate pathway, and thus, for example, the buildup of cholesterol.

2 NADPH / H CoA -SH 2 NADP

HMG -CoA is reduced to mevalonate.

5 -phospho -R - mevalonate

The phosphorylation of mevalonate through the mevalonate kinase takes place in the cytosol.

ATP ADP

R- mevalonate is converted to 5 -phospho -R - mevalonate. One molecule of ATP is consumed.

5 - diphospho -R - mevalonate

Another phosphorylation leads to 5 - Pyrophosphomevalonat. Catalyst is here phosphomevalonate kinase, which has only been found in the peroxisomes.

ATP ADP

5 -phospho -R - mevalonate is converted to 5 - diphospho -R - mevalonate.

Isopentenyl pyrophosphate

The last reaction step, the IPP catalyzed by the Diphosphomevalonat decarboxylase decarboxylation of Diphosphomevalonat; they take place in the cytosol.

ATP ADP Pi CO2

5 - diphospho -R mevalonate is converted to isopentenyl pyrophosphate (IPP).

Dimethylallyl

The isomerization of IPP to DMAPP reciprocal and vice versa is catalyzed by isopentenyl diphosphate isomerase. Both isoforms of the enzyme were localized in peroxisomes.

Isopentenyl diphosphate (IPP ) and dimethylallyl diphosphate (DMAPP ) merge.