[Previous] | [Next]

Basic Energy Concepts
Types of Catabolism
Feremented Foods
Catabolism of Fats
Catabolism of Proteins
Amazing Respirations
Membranes and
Energy Generation

Anaerobic Respiration
Summary of Catabolism
Collecting Elements
Synthesizing Monomers
Carbon Assimilation
Nitrogen Assimulation
Other Assimilation
Formation of
Amino Acids

Lipid Synthesis
Nucleotide Synthesis
Making Polymers
Structural Assembly
Amphibolic Pathways

Search | Send us your comments

Synthesis of Amino Acids

©2000 Timothy Paustian, University of Wisconsin-Madison

Synthesis and/or collection of amino acids is critical for cell survival. They not only serve as the building blocks for proteins but also as starting points for the synthesis of many important cellular molecules including vitamins and nucleotides.

In most cases bacteria would rather use amino acids in their environment than make them from scratch. It takes a considerable amount of energy to make the enzymes for the pathway as well as the energy required to drive some of the reactions of amino acid biosynthesis. The genes that code for amino acid synthesis enzymes and the enzymes themselves are under tight control and are only turned on when they are needed.

The amino acids synthesis pathways can be grouped into several logical units. These units reflect either common mechanisms or the use of common enzymes that synthesize more than one amino acid. These categories are: simple reactions, branch chain amino acids, aromatic amino acids, threonine/lysine, serine/glycine, and unique pathways. The aromatic amino acids, threonine/lysine and serine/glycine pathways have a common beginning and then diverge to form the amino acid of interest.

Notice that each pathway begins with a central metabolite or something derived from "central metabolism". Using common compounds instead of synthesizing them from scratch saves energy and conserves genes since fewer enzymes are needed to code for the pathways.

Simple Reactions

glutamine, glutamate, aspartate, asparagine and alanine

In most cases these amino acids can be synthesize by one step reactions from central metabolites. They are simple in structure and their synthesis is also straight forward.

Glutamate can by synthesized by the addition of ammonia to a-ketoglutarate.

glutamatesyn picture

Figure 1 - The synthesis of glutamate.

Glutamine is made by the addition of another ammonia molecule to glutamate.

glutaminesyn picture

Figure 2 - Synthesis of glutamine

The rest of the simple reactions involve transfer of the amino group (transamination) from glutamate or glutamine to a central metabolite to make the required amino acid. Aspartate is synthesize by the transfer of a ammonia group from glutamate to oxaloacetate.

aspartatesyn picture

Figure 3 - The synthesis of aspartate.

Asparagine is made either by transamination from glutamine or by adding ammonia directly to aspartate.

asparginesyn picture


asparaginesyn2 picture

Figure 4 - Formation of asparagine. Notice the use of AMP instead of ADP in this reaction. This releases more energy which is needed to drive the synthesis.

Alanine synthesisis is a bit of a mystery. Several reactions have been identified, but it has been impossible to generate an alanine auxotroph and therefore positively identify a required pathway. There are several pathways and the most likely is formation of alanine by transamination from glutamate onto pyruvate. A transamination using valine instead of glutamate is also possible.

alaninesyn picture

Figure 5 - Synthesis of alanine


Synthesis of threonine and lysine begins by the conversion of oxaloacetate to aspartate semialdehyde. This shared pathway costs one ATP and two NADPH + H+

Threonine biosynthesis is completed in three steps. First a second reduction with NADPH + H+, yields homoserine. This is phosphorylated to homoserine phosphate by ATP and finally converted into threonine.

lysthrsyn picture

Figure 6 - Synthesis of Threonine and Lysine. Note the amount of energy that is expended in these biosytheses.

The synthesis of lysine has been found to consist of different reactions in different bacterial species. A somewhat generalize pathway is presented. Lysine synthesis involves the addition of pyruvate to aspartate semialdehyde, the use of a CoA intermediate (either acetyl CoA or succinyl-CoA) and the addition of an amino group from glutamate. The group added from CoA (either succinyl or acetyl) serves as a blocking group, protecting the amino group from attack during transamination by glutamate. NADPH + H+ is required for reduction in the second step of the pathway.


The biosynthesis of serine and glycine constitute a major metabolic pathway that plays a central role in the formation of other amino acids, nucleic acids and phospholipids. When E. coli is grown on glucose, fully 15% of carbon assimilated passes through the serine pathway. Synthesis of serine and glycine starts with oxidation of 3-phosphoglycerate forming 3-phosphohydroxy pyruvate and NADH. A transamination reaction with glutamate forms 3-phosphoserine and removal of the phosphate yields serine. Glycine is generated by removal of the methyl group from serine. Energy is not required for this pathway, in fact it yields energy in the form of reduced NADH.

serglysyn picture

Figure 7 - Synthesis of Serine and Glycine. Note that this pathway actually yields energy and carbon for other uses. R (tetrahydropholate)

Branch chain amino acids

leucine, isoleucine and valine

Examination of the isoleucine pathway versus the valine pathway demonstrates that the only difference is the substitution of an ethyl group instead of a methyl group to the a-carbon of the intermediates.The intermediates are so similar that common enzymes catalyze four steps of each pathway. Isoleucine synthesis begins with threonine, which is deaminated to a-ketobutyrate. From here the 4 step synthesis costs one NADPH + H+ per amino acid synthesized.

isovalsyn picture

Figure 8 - Synthesis of valine and isoleucine.

Leucine biosynthesis starts of with the last intermediate in the valine synthesis, a-ketoisovalerate. In the first step Acetyl-CoA is used to add an acetyl group to the molecule. Electrons are transferred to NAD+ (note these can be used for other cellular processes) and one carbon is lost in the form of CO2 at the fourth step of the pathway. In the final step, the amine from glutamate is added to a-ketoisocaproate to form leucine.

leusyn picture

Figure 9 - Synthesis of leucine.

Aromatic amino acids

tryptophan, phenylalanine and tyrosine

Synthesis of the aromatic amino acids begins with the synthesis of chorismate - an important intermediate for many biosynthetic pathways. Phosphoenol pyruvate and erythrose 4-phosphate serve as beginning substrates for the pathway. A price of one NADPH + H+ and one ATP is exacted for every chorismate formed. In the sixth step of the synthesis another phosphoenol pyruvate molecule is added to the growing molecule.

chorissyn picture

Figure 10 - Synthesis of chorismate


Chorismate is converted to phenylpyruvate in two steps and phenylalanine is synthesized by a transamination reaction with glutamate. No energy is require to run these reactions.

phesyn picture

Figure 11 - Synthesis of phenylalanine.


The synthesis of tyrosine is very similar to the synthesis of phenylalanine, but the reactions are carried out by different enzymes under different regulatory control. NADH is created in the formation of 4-hydroxyphenylpyruvate. Tyrosine is made by a similar transamination reaction as that seen in phenylalanine synthesis.

tyrsyn picture

Figure 12 - Synthesis of tyrosine.


Trytophan synthesis is complex and involves 5 steps from chorismate. Glutamate donates an amine group in the first step of the pathway and pyruvate is lost from chorismate. In the next threes steps a ribose sugar is added, this eventually contributes to the 5 membered ring of tryptophan. Energy is contributed to the process in the form of hydrolysis of pyrophosphate. This hydrolysis helps drive the addition of the ribose sugar in the second step of the reaction. In the last step of the pathway serine serves as the donor of the a carbon amino group of tryptophan.

trpsyn picture

Figure 13 - Synthesis of tryptophan.

Unique pathways

cysteine, methionine, proline, histidine and arginine

These pathways involve something unusual, either the structure of the amino acid is different enough than the other common amino acids, or sulfur is involved in their synthesis. In any case, unique enzymes are involved in every step of the way. Here we just examine what they start with and how much it costs the cell.


Synthesis of cysteine is a two step reaction. Serine and acetyl-CoA combine to form O-acetylserine. Sulfide from sulfur assimilation is then added to O-acetylserine to form cysteine. The pathway for cysteine synthesis was covered in sulfate assimilation.


Methionine is synthesized from oxaloacetate. Succinyl-CoA participates and cysteine donates a sulfur group to the molecule. Oxaloacetate is first converted into homoserine as described above in the threonine biosynthetic pathway. Homoserine then has a sulfur attached to the end in two steps and finally methionine is formed by the addition of a methyl group.

metsyn picture

Figure 14 - Synthesis of methionine. The donor of the methyl group (R) is a methyl carrier in the cell, N5,N10-Methylene terahydropteroyl.


Proline synthesis involves a four step process starting with glutamate. One ATP and two NADPH + H+ is used per proline.

prosyn picture

Figure 15 - Synthesis of proline.


The synthesis of histidine is long and complex and its pathway is intertwined with nucleic acid biosynthesis (specifically purine). The pathway seems to be universal in all organisms able to synthesize histidine. The first five steps of the pathway take ribose from phosphoribosyl pyrophosphate (PRPP) and transform it into Imadiazoleglycerol phosphate. Once the imadiazole ring is formed, glutamate donates the a-amino group and the newly formed amine is oxidized to histidine in the last step of the pathway. Energy is required in the form of ATP (in this case elements of the ATP molecule actually becomes part of the amino acid) and pyrophosphate which is lost from phosphoribosyl pyrophosphate and ATP help drive the reaction.

hissyn picture

Figure 16 - Synthesis of Histidine

Investigations into histidine biosynthesis have yielded many insights into microbial metabolism that have contributed greatly to our understanding of how cells function at the genetic and biochemical level. Work in this area is still yielding important results.


Synthesis of arginine is an eight step process starting with the amino acid glutamate. Two ATP and one NADPH + H+ are utilized to synthesize each arginine.

argsyn picture

Figure 17 - Synthesis of arginine.

[Previous] | [Next]

frontierlogo picture This page was last built with Frontier and Web Warrior on a Macintosh on Thu, Sep 21, 2000 at 1:16:12 PM.