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Leucine (LEU), Valine (VAL), Isoleucine (ILE) and Histidine (HIS) Metabolism

by Kevin Ahern, PhD
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    The three amino acids leucine, valine and isoleucine are the next ones I want to consider. Notice the branched-chain amino acids, the BCAAs, and they have some common features among them in their metabolism and some unique features as well. We start with them in their decarboxylation by the attachment of a two-carbon piece to a molecule known as thiamine pyrophosphate. Now valine and leucine pathways involve attachment of this two-carbon piece to pyruvate. They have that in common. The isoleucine pathway, by contrast, involves the attaching of this two-carbon piece to a molecule of aplah-ketobutyrate. The penultimate products that is the precursors of these amino acids then become the following molecules. Alpha-ketoisocaproate is a precursor of leucine by a transamination reaction. Alpha-ketoisovalerate is a precursor of valine, again, by a transamination. And finally, alpha-keto-beta-methylvalerate is a precursor of isoleucine, a third transamination. Now, the synthesis of these amino acids is important to balance. One of the themes that we've seen in metabolic pathways is the importance of making the right amount, not too much, not too little, of any given molecule. And this is illustrated in the slide that I want to show here for these three amino acids. Now, the synthesis of these three amino acids actually interacts with the synthesis of the breakdown pathway for threonine. Threonine's breakdown involves the enzyme threonine deaminase. We can see that illustrated at the top left of the screen. The breakdown of threonine produces the molecule alpha-ketobutyrate. And if you recall from what I said earlier, alpha-ketobutyrate is the precursor of isoleucine that involves the transfer of a two-carbon piece from thiamine pyrophosphate. It's that transfer that produces the precursor that ultimately makes isoleucine and that's shown in the sort of central part of the screen. We remember that there is...

    About the Lecture

    The lecture Leucine (LEU), Valine (VAL), Isoleucine (ILE) and Histidine (HIS) Metabolism by Kevin Ahern, PhD is from the course Amino Acid Metabolism. It contains the following chapters:

    • Leucine (LEU)/Valine (VAL)/Isoleucine (ILE) Metabolism
    • Histidine (HIS) Metabolism

    Included Quiz Questions

    1. ...is regulated by threonine deaminase.
    2. ...begins with α-ketobutyrate.
    3. ...favors isoleucine when valine is low.
    4. All of the answers are true.
    5. None of the answers are true.
    1. All of the answers are true.
    2. It starts with decarboxylation.
    3. It produces NADH.
    4. When defectiveIt, results in maple syrup urine disease.
    5. None of the answers are true.
    1. It overlaps with carbohydrate and nucleotide metabolism.
    2. It arises from tryptophan metabolism.
    3. It involves 15 steps.
    4. All of the answers are true.
    5. None of the answers are true.

    Author of lecture Leucine (LEU), Valine (VAL), Isoleucine (ILE) and Histidine (HIS) Metabolism

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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