SQUALENE MONOOXYGENASE

Todd D. Porter, Ph.D.

Squalene monooxygenase (formerly squalene epoxidase) catalyzes the second committed (and likely rate-limiting) step in cholesterol biosynthesis from farnesyl pyrophosphate, making it an attractive pharmacotherapeutic target in the management of hypercholesterolemia and resultant cardiovascular disease.  In neural tissue squalene monooxygenase plays an essential role in the synthesis of cholesterol necessary for myelin membranes, and has been identified as the site of inhibition by tellurium-containing compounds that cause a peripheral neuropathy.  But, despite its pivotal role in cholesterol biosynthesis, remarkably little is known about this enzyme, especially in man.

Studies in my laboratory are directed at generating structural and biochemical information on squalene monooxygenase that will help us to understand its mechanism of action, its interaction with other proteins in the cell, and its inhibition by tellurium- and selenium-containing compounds.

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• Biology of squalene monooxygenase

  • Discovery and Characterization

  • Regulation of Expression

  • Therapeutic and Natural Inhibitors
    
    

• The squalene monooxygenase family and related enzymes

  • Squalene Monooxygenase Sequences

  • Alignment of Squalene Monooxygenases

  • Other Flavoproteins Related to Squalene Monooxygenase

  • Comparison of Squalene Monooxygenase to p-Hydroxybenzoate Hydroxylase

  • The 3-Dimensional Structure of p-Hydroxybenzoate Hydroxylase
    
    

• Enzymology of squalene monooxygenase

  • Mechanism

  • Interaction with Cytochrome P450 Reductase

  • Interaction with Squalene and FAD
    
    

• Inhibition by tellurium and selenium compounds

  • Chemistry and Toxicity of Tellurium and Selenium

  • Inhibition of Squalene Monooxygenase by Tellurium and Selenium

  • Tellurium and Selenium Compounds React with Cysteines on Squalene Monooxygenase
    
    
    

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