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22.2: Biosynthesis of Amino Acids

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    15179
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    Introduction

    By the time many students get to the study of amino acid biosynthesis, they have seen so many pathways that learning new pathways for the amino acids seems daunting, even though they can be clustered into subpathways.   Most know that from a nutrition perspective, the amino acids can be divided into nonessential and essential (need external dietary supplementation) amino acids.  These are shown for humans below.

    • Nonessential amino acids: Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, Serine, Tyrosine
    • Essential amino acids: Arginine*, Histidine, Isoleucine, Leucine, Lysine, Methionine*, Phenylalanine*, Threonine, Tryptophan, Valine

    Three of the essential amino acids can be made in humans but need significant supplementation. Arginine is depleted in processing through the urea cycle. When cysteine is low, methionine is used to replace it so its levels fall. If tyrosine is low, phenylalanine is used to replace it. 

    The amino acids can be synthesized from glycolytic and the citric acid cycle intermediates as shown in Figure \(\PageIndex{1}\) below

     

    summaryAASyntheis_TCA_GlycolysisV2.svg

    Figure \(\PageIndex{1}\): Summary amino acid synthesis from glycolytic and TCA intermediates

    For this chapter subsection, we will provide only the basic synthetic pathways in abbreviated form without going into mechanistic or structural details 

    Amino acid synthetsis from glycolytic intermediates

    From Glucose-6-Phosphate: Histidine

    The synthesis of histidine from a phosphorylated form of ribose (derived from glucose-6-phosphate) is shown in Figure \(\PageIndex{2}\) below.

    His_SynthesisV2.svg

    Figure \(\PageIndex{2}\):  Synthesis of histidine from a phosphorylated form of ribose

     

    From 3-phosphoglycerate: Serine, Glycine and Cysteine

    The synthesis of serine, glycine and cysteine from 3-phosphoglycerate is shown in Figure \(\PageIndex{3}\) below.

    SerGlyCys_Synthesis.svg

    Figure \(\PageIndex{3}\):  The synthesis of serine, glycine and cysteine from 3-phosphoglycerate 

     

    From Phosphenol Pyruvate: The Aromatics - Trp, Phe and Tyr

    The synthesis of the first of the biosynthetic pathways for the aromatic amino acids phenylalanine, tryptophan and tyrosine from phosphoenolpyruvate up to chorismate are shown in Figure \(\PageIndex{4}\) below.  

    Shikimage_Synthesis_commontoAromaticAAsyn.svg

    Figure \(\PageIndex{4}\):  Synthesis of the first of the biosynthetic pathways for the aromatic amino acids phenylalanine, tryptophan and tyrosine from phosphoenolpyruvate up to chorismate 

    Chorismate to tryptophan

    The synthesis of the second half of the biosynthetic pathway for tryptophan from chorismate is shown in Figure \(\PageIndex{5}\) below

    ChoristmatentoTrpSyn.svg

    Figure (\PageIndex{5}\): Synthesis of the second half of the biosynthetic pathways for the aromatic amino acid tryptophan from chorismate 

     

    Chorismate to Phe and Tyr

    The synthesis of the second half of the biosynthetic pathway for phenyalanine and tyrosine from chorismate is shown in Figure \(\PageIndex{6}\) below

    ChoristmatentoPheTyrSyn.svg

     Figure \(\PageIndex{6}\):  Synthesis of the second half of the biosynthetic pathway for phenyalanine and tyrosine from chorismate 

     

    From Pyruvate: Ala, Val, Leu, Ile

    Ala can easily be synthesized from the alpha-keto acid pyruvate by a transamination reaction, so we will focus our attention on the others, the branched chain nonpolar amino acid Val, Leu, and Ile.

    The synthesis of valine, leucine, and isoleucine from pyruvate is shown in Figure \(\PageIndex{7}\) below.

    Val_Ile_Leu_Synthesis.svg

    Figure \(\PageIndex{7}\): The synthesis of valine, leucine, and isoleucine from pyruvate

    TCA Intermediates

    From α-ketogluatarate: Glu, Gln, Pro, Arg

    Since amino acid metabolism is so complex, it's important to constantly review past learning. Figure \(\PageIndex{8}\) below from section 18.2 shows the relationship among Glu, Gln and keto acids.

    metabolismWP_GlnMet4.svg

    Figure \(\PageIndex{8}\):  Glutamate and glutamine synthesis from α-ketoglutarate

    As is evident from the figure, glutamic acid can be made directly through transamination of α-ketoglutarate by an ammonia donor, while glutamine can be made by the action of glutamine synthase on glutamic acid.

    Arginine is synthesized in the urea cycle as we have seen before. It can be made from α-ketoglutarate through the following sequential intermediates: N-acetylglutamate, N-acetylglutamate-phosphate, N-acetylglutamate-semialdehyde, N-acetylornithine to N-acetylcitruline. The is deacetylated to and enters the urea cycle.

    The pathway for conversion of α-ketoglutarate to proline is shown in Figure \(\PageIndex{9}\) below. 

    ProSynthesis.svg

     

    Figure \(\PageIndex{9}\): Conversion of α-ketoglutarate to proline

    From oxalacetate: Asp, Asn, Met, Thr, Lys

    OAA to Aspartatic Acid

    This is a a simple transamination

    Aspartic Acid to Asparagine

    This is catalyzed by the enzyme Asparagine Synthase as show in the reaction equation below:

    Aspartate + Glutamine + ATP + H2O  → Asparagine + Glutamic Acids + AMP + PPi 

    Aspartic Acid to Lysine

    There are two pathways. 

    • The diaminopimelic acid (DAP) pathway uses aspartate and pyruvate  and forms diaminopimelic acid as an intermediate.  Its found in bacteria, some fungi and archaea and in plants. 
    • The aminoadipic acid (AAA) pathways uses α-ketoglutarate and acetyl-CoA and forms aminoadipic acid as an intermediate. It is used by fungi.,

    Here we present just the synthesis of lysine from aspartate and pyruvate using the diaminopimelic acid DAP pathway.  The pathway is shown in Figure \(\PageIndex{10}\) below.

     

    LysSynthesis.svg

    Figure \(\PageIndex{10}\): The synthesis of lysine from aspartic acid in the diaminopimelic acid DAP pathway

    .

    Aspartic acid to Threonine

    The conversion of aspartic acid to threonine is shown in Figure \(\PageIndex{11}\) below.

    ThrSynthesis.svg

    Figure \(\PageIndex{11}\):  The conversion of aspartic acid to threonine

    Aspartic acid to Methionine

    The conversion of aspartic acid to methionine is shown in Figure \(\PageIndex{12}\) below.

    MetSynthesis.svg

    Figure \(\PageIndex{12}\):  The conversion of aspartic acid to methionine


    22.2: Biosynthesis of Amino Acids is shared under a not declared license and was authored, remixed, and/or curated by Henry Jakubowski.

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