22.2: Biosynthesis of Amino Acids
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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, 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 citric acid cycle intermediates as shown in Figure \(\PageIndex{1}\)
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 synthesis 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 \(\PageIndex{2}\).
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 \(\PageIndex{3}\).
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 is shown in Figure \(\PageIndex{4}\).
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 \(\PageIndex{5}\)
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 phenylalanine and tyrosine from chorismate is shown in Figure \(\PageIndex{6}\)
Figure \(\PageIndex{6}\): Synthesis of the second half of the biosynthetic pathway for phenylalanine 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 acids Val, Leu, and Ile.
The synthesis of valine, leucine, and isoleucine from pyruvate is shown in Figure \(\PageIndex{7}\).
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 \(\PageIndex{8}\) from section 18.2 shows the relationship among Glu, Gln, and keto acids.
Figure \(\PageIndex{8}\): Glutamate and glutamine synthesis from α-ketoglutarate
As is evident from the figure, glutamic acid can be made directly through the 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 and enters the urea cycle.
The pathway for conversion of α-ketoglutarate to proline is shown in Figure \(\PageIndex{9}\).
Figure \(\PageIndex{9}\): Conversion of α-ketoglutarate to proline
From oxalacetate: Asp, Asn, Met, Thr, Lys
OAA to Aspartatic Acid
This is a simple transamination
Aspartic Acid to Asparagine
This is catalyzed by the enzyme Asparagine Synthase as shown 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. It's found in bacteria, some fungi, and archaea and in plants.
- The aminoadipic acid (AAA) pathway 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 \(\PageIndex{10}\).
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 \(\PageIndex{11}\).
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 \(\PageIndex{12}\).
Figure \(\PageIndex{12}\): The conversion of aspartic acid to methionine