Cholesterol Biosynthesis

 

Structural drawing of Cholesterol and acetyl CoA

  1. Synthesis of delta3-Isopentyl PPi (IPP, 5 C) from acetyl CoA.

  2. IPP (5 C) + IPP (5 C) right arrow Geranyl PPi (GPP, 10 C).

  3. GPP (10 C) + IPP (5 C) right arrow Farnasyl PPi (FPP, 15 C).

  4. FPP (15 C) + FPP (15 C) right arrow Squalene (30 C).

 

 

 

 

 

 

 

 

 

 

Synthesis of delta3-Isopentyl PPi (IPP, 5 C) from acetyl CoA, Step 1: Condensation of two acetyl CoA's to give acetoacetyl CoA (4 C):

structural diagram of the condensation two acetyl CoA's to give acetoacetyl CoA

 

 

 

 

 

 

 

 

 

 

 

 

Synthesis of delta3-Isopentyl PPi (IPP, 5 C) from acetyl CoA, Step 2: Acetyl CoA is condensed to give HMG (3-hydroxy-3-methylglutaryl CoA, 6 C):

Structural diagram of the condensation of acetoacetyl CoA and acetyl CoA to give HMG (3-hydroxy-3-methylglutaryl CoA

 

 

 

 

 

 

 

 

 

 

 

 

Synthesis of delta3-Isopentyl PPi (IPP, 5 C) from acetyl CoA, Steps 3 & 4: HMG-CoA is now reduced by HMG-CoA reductas to give mevalonate:

Structural diagram of the reaction sequence converting HMG-CoA to Mevelonate

 

 

 

 

 

 

 

 

 

 

 

 

 

Synthesis of delta3-Isopentyl PPi (IPP, 5 C) from acetyl CoA, Steps 5 & 6: Mevalonate is now phosphorylated twice, first by by mevalonate-5-phosphotransferase and then by phosphomevalonate kinase to give 5-pyrophophomevalonate:

Structural diagram of the reactions phosphorylating mevelonate to 5-Pyrophophomevelonate

 

 

 

 

 

 

 

 

 

 

 

 

 

Synthesis of delta3-Isopentyl PPi (IPP, 5 C) from acetyl CoA, Step 7: The 5-pyrophophomevalonate is decarboxylated by pyrophophomevalonate decarboxylase to give 3-Isopentyl PPi (3-Isopentene is the so-called "isoprene unit", 5 C):

Structural diagram of the decarboxylation of 5-pyrophophomevelonate to give delta 3- isopentyl pyrophosphate

 

 

 

 

 

 

 

 

 

 

 

 

 

In the next reaction sequence two isopentyl units (5 C) are joined to give geranyl PPi in two reactions:

 

Structural diagram of the isomerization of IPP to DPP

 

Structural diagram of the condensation of IPP and DPP to give GPP

 

 

 

 

 

 

 

 

 

 

 

 

 

We now add a third IPP to the GPP to give farnesyl pyrophosphate (FPP, 15 C).

Structural diagram of the condensation of IPP and GPP to give FPP

 

 

 

 

 

 

 

 

 

 

 

 

Squalene synthase now catalyzes the head-to-head condensation of two farnesyl pyrophosphates:

Structural diagram of the condesation of two FPP to give squalene

 

 

 

 

 

 

 

 

 

 

 

 

 

Squalene is converted to a sterol, Lanosterol (30 C) by two enzymes, Squalene epoxidase and Squalene oxidocyclase:

Structural diagram of the Squalene epoxidase reaction

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Structural diagram of the cyclization reaction catalyzed by Squalene oxidocyclase

 

 

 

 

 

 

 

 

Structural diagram of the hydride and methyl migrations catalysed by Squalene oxidocyclase

 

Pathway Diagrams

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Last modified 2 February 2009