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The Metabolism of Lipids 

In this project I will discuss the anabolism and catabolism of lipids and steroids.  The steps in the pathways from reactants to products will be mentioned.  Remember that anabolism is the synthesis of organic molecules and catabolism is the use of these molecules.
 

Catabolic Pathways and Lipids

Energy requirements for biological organisms are extensive.  Average recommended caloric allowances for adults range from 2500 to 3500 kilo calories per day, based on body mass, age, and activity levels.  Most organisms are heterotrophs, and rely on plant and animal sources for their energy supply.  One source of energy is lipids, provided by numerous food sources, particularly dairy products.  The following pathway reduces lipids to the end product Acetyl-CoA.

Catalysis of Lipids to Acetyl-CoA and Reduced Electron Carriers

Acetyl-CoA comes from the Beta-oxidation of lipids.  It is called beta-oxidation because the beta-carbon is always oxidized as the first step in the process.  The process involves a series of steps that each releases a two-carbon fragment, which is acetyl-CoA.  This beta-oxidation pathway is cyclic -- in each step, the substrate is an acyl-CoA, which is shortened (by formation of the acetyl-CoA) by two carbons.  The product, a new, shorter acyl-CoA, then undergoes the same reaction again.

From chapter 18 in the text, there are four steps in each time a new acetyl-CoA is formed from an acyl-CoA substrate:

  1. 1: Dehydrogenation of the saturated fatty acyl-CoA to give an enoyl derivative, then:
  2. 2: Hydration of the resulting double bond and hydroxylation of the beta-carbon;
  3. 3: Dehydrogenation of the hydroxyl group;
  4. 4: A second molecule of acetyl-CoA attacks the beta-carbon, releasing acetyl-CoA and a fatty acyl-CoA (with the number of           carbons dropped by two).

Anabolic Pathways to Lipids

Some microorganisms (autotrophs) produce their own food, and they can use the following pathways to create lipids.  These pathways are also responsible for the creation of steroids, which are a physiological requirement for most organisms.  The synthesis of fatty acids is not simply the reverse of the catabolism pathways.  Different electron carriers are used, and there are differences in the stereochemistry of the reactions.  A main similarity is that two carbon fragments are added to form the new lipids.  Since this topic has not been studied in significant detail, we will, for the time being, study the process by which acetyl-CoA is used to synthesize lipids.

Acetyl Coenzyme-A and the Biosynthesis of Lipids

Referring again to chapter 18, we can discuss the process of lipid synthesis from acetyl-CoA.
  • To begin, palmitate is synthesized from acetyl-CoA.
  • Palmitate is elongated, two carbons at a time.
  • The resulting lipid is desaturated.
  • The first step, synthesis of palmitate, occurs as a cycle of four reactions:

    1. 1: Condensation
    2. 2: Reduction
    3. 3: Dehydration
    4. 4: Reduction
    This cycle repeats four times.  Elongation of the chain occurs by a condensation, then a reduction, a dehydration, and another reduction.  This results in a saturated fatty acyl-CoA two carbons longer than the original substrate.  The desaturation occurs by enzyme systems such as fatty acyl-CoA desaturase.
     

    Research Involving Metabolism and Lipids

    Among the leading causes of health problems among neonates (infants under 30 days of age) are metabolic disorders.  These include problems associated with breakdown and storage of lipids.  Research is under way that would help resolve problems with lipid metabolism, such as with enzyme replacement therapy.
     
     

    Project Links

    An overview of metabolism -- Stan's page
    Oxidative Phosphorylation...and much more -- Leah's page
    Carbohydrate Catabolism -- Rod's Page
    Metabolism -- Project 7 Main Page