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

 


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Last modified 2 February 2009