The transamination is a type of chemical reaction that operates in the "redistribution" of the amino groups from amino acids, because it involves reversible processes amination (addition of an amino group) and deamination (removal of an amino group), which are catalyzed by specific enzymes known as transaminases or aminotransferases.
The general transamination reaction involves the exchange between an amino acid and any α-keto acid, where the exchange of an amino group yields the ketoacid version of the first substrate amino acid and the amino acid version of the first substrate α-keto acid.
Graphic scheme of an aminotransfer reaction between an amino acid and an alpha-keto acid (Source: Alcibiades Via Wikimedia Commons)
The amino group that is usually exchanged is the "alpha" amino, that is, the one that participates in the formation of peptide bonds and that defines the structure of amino acids, although reactions involving other amino groups present in different positions can also occur..
With the exception of lysine, threonine, proline and hydroxyproline, all amino acids participate in transamination reactions, although transaminases have been described for histidine, serine, methionine and phenylalanine, but their metabolic pathways do not involve this type of reactions.
Transamination reactions between amino acids and α-keto acids were discovered in 1937 by Braunstein and Kritzmann, and since then they have been the subject of intensive studies, as they occur in many tissues of different organisms and for different purposes.
In humans, for example, transaminases are widely distributed in body tissues and are particularly active in cardiac muscle tissue, the liver, skeletal muscle tissue, and the kidneys.
Reaction mechanism
Transamination reactions involve more or less the same mechanism. As discussed earlier, these reactions occur as a reversible exchange of an amino group between an amino acid and an α-keto acid (deaminated), producing the α-keto acid of the donor amino acid and the amino acid of the α-keto acid receptor.
These reactions depend on a compound known as pyridoxal phosphate, a derivative of vitamin B6 that participates as a transporter of amino groups and that binds to transaminase enzymes through the formation of a Schiff's base between the aldehyde group of this molecule. and the ε-amino of a lysine residue in the active site of the enzyme.
The bond between pyridoxal phosphate and the lysine residue in the active site is not covalent, but occurs through the electrostatic interaction between the positive charge of nitrogen on lysine and the negative charge on the phosphate group of pyridoxal.
In the course of the reaction, the amino acid that functions as a substrate displaces the ε-amino group of the lysine residue in the active site that participates in the Schiff's base with pyridoxal.
Meanwhile, a pair of electrons from the alpha carbon of the amino acid are removed and transferred to the pyridine ring that makes up pyridoxal phosphate (positively charged) and then "delivered" to the α-keto acid that functions as a second substrate.
In this way, pyridoxal phosphate not only participates in the transfer or transport of amino groups between amino acids and α-ketoacids that are substrates of transaminases, but also acts as a “sink” of electrons, facilitating the dissociation of the alpha amino acid hydrogen.
In summary, the first substrate, an amino acid, transfers its amino group to pyridoxal phosphate, from where it is subsequently transferred to the second substrate, an α-keto acid, forming, in the meantime, an intermediate compound known as pyridoxamine phosphate.
Function of transamination
Transaminase enzymes are generally found in the cytosol and mitochondria and function in the integration of different metabolic pathways.
Glutamate dehydrogenase in its reverse reaction, for example, can convert glutamate to ammonium, NADH (or NADPH), and α-ketoglutarate, which can enter the tricarboxylic acid cycle and function in energy production.
This enzyme, which is in the mitochondrial matrix, represents a branch point that associates amino acids with energy metabolism, so that when a cell lacks enough energy in the form of carbohydrates or fats to function, it can alternatively use some amino acids for the same purpose.
The formation of the enzyme (glutamate dehydrogenase) during brain development is essential for the control of ammonium detoxification, since it has been shown that some cases of mental retardation have to do with a low activity of this, which leads to ammonium buildup, which is detrimental to brain health.
In some liver cells, transamination reactions can also be used for the synthesis of glucose by gluconeogenesis.
Glutamine is converted to glutamate and ammonium by the enzyme glutaminase. Next, glutamate is converted to α-ketoglutarate, which enters the Krebs cycle and then gluconeogenesis. This last step occurs thanks to the fact that malate, one of the products of the route, is transported to the outside of the mitochondria by means of a shuttle.
This shuttle leaves α-ketoglutarate at the mercy of the malic enzyme, which converts it to pyruvate. Two pyruvate molecules can then be converted to one glucose molecule through gluconeogenesis.
Examples
The most common transamination reactions are related to the amino acids alanine, glutamic acid, and aspartic acid.
Some aminotransferase enzymes can, in addition to pyridoxal phosphate, use pyruvate as a “coenzyme”, as is the case of glutamate-pyruvate transaminase, which catalyzes the following reaction:
glutamate + pyruvate ↔ alanine + α-ketoglutarate
Muscle cells depend on this reaction to produce alanine from pyruvate and to obtain energy through the Krebs cycle through α-ketoglutarate. In these cells, the use of alanine as a source of energy depends on the elimination of amino groups as ammonium ions in the liver, through the urea cycle.
Alanine transamination reaction (Source: Tomas Drab via Wikimedia Commons)
Another very important transamination reaction in different species is that catalyzed by the enzyme aspartate aminotransferase:
L-Aspartate + α-Ketoglutarate ↔ Oxaloacetate + L-Glutamate
Last but not least, the transamination reaction of γ-aminobutyric acid (GABA), a non-protein amino acid essential for the central nervous system that functions as an inhibitory neurotransmitter. The reaction is catalyzed by a γ-aminobutyric acid transaminase and is more or less as follows:
α-Ketoglutarate + 4-aminobutanoic acid ↔ Glutamate + Succinic semialdehyde
Succinic semialdehyde is converted to succinic acid through an oxidation reaction and the latter can enter the Krebs cycle for energy production.
References
- Bhagavan, NV, & Ha, CE (2002). Protein and amino acid metabolism. Medical Biochemistry (4th ed.), Academic Press: San Diego, CA, USA, 331.
- Cammarata, PS, & Cohen, PP (1950). The scope of the transamination reaction in animal tissues. Journal of Biological Chemistry, 187, 439-452.
- Ha, CE, & Bhagavan, NV (2011). Essentials of medical biochemistry: with clinical cases. Academic Press.
- Litwack, G. (2017). Human biochemistry. Academic Press.
- Rowsell, EV (1956). Transaminations with pyruvate and other α-keto acids. Biochemical Journal, 64 (2), 246.
- Snell, EE, & Jenkins, WT (1959). The mechanism of the transamination reaction. Journal of cellular and comparative physiology, 54 (S1), 161-177.