ALANINE: CHARACTERISTICS, STRUCTURE, FUNCTIONS, BIOSYNTHESIS - BIOLOGY - 2024

The alanine (Ala) is one of the 22 known amino acids that comprise the protein structure of all organisms, from bacteria to man. Because it can be synthesized by the body, it is classified as a nonessential amino acid.

Proteins have a basic or primary structure made up of a chain of amino acids called polypeptide chain, in these chains each amino acid is made up of a central carbon called α carbon.

Chemical structure of the amino acid Alanine (Source: Borb, via Wikimedia Commons)

The α carbon is attached to four groups: an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom (-H), and a group or side chain (-R) that identifies each amino acid. In the side chain, the carbons take sequentially the letters ß, γ, δ and ε.

Amino acids are classified by the polarity of their side chains and thus there are apolar hydrophobic and polar hydrophilic amino acids that, in turn, can be neutral, basic and acidic. Alanine is a hydrophobic apolar amino acid and is the simplest amino acid after glycine and the most abundant in most proteins.

Alanine can be formed in muscle and transported to the liver, where it is introduced to the gluconeogenic pathway, that is, the pathway for the formation of glucose from non-glycosidic substances. Alanine can also be synthesized in the liver through the catabolism of tryptophan and uracil and can be broken down to form pyruvate.

It participates in the synthesis of tryptophan, pyridoxine (Vitamin B6) and carnosine and, as it can be converted into pyruvate, it indirectly participates in the regulation of glycemia or as a source of energy for skeletal muscle.

It is used as a dietary supplement to improve sports performance and is found naturally in beef, pork and fish, as well as in milk and its derivatives and in eggs. Some legumes, fruits, and nuts are also rich in alanine.

Structure

It was discussed earlier that alanine, like all amino acids, has an α-carbon with four groups attached to it, the R group being a methyl group (-CH3).

Therefore, at body pH (around 7.4) the α-carbon of alanine is attached to a protonated amino group (-NH3 +), a carboxyl group that has lost a proton (-COO-), a hydrogen and a methyl group (-CH3).

Most amino acids are ionizable at pH 7.0 and geometrically they can have isomers, which are known as enantiomers, which are mirror images, just like the right and left hand.

Then, all amino acids can be found as "chiral pairs" denoted as D or L (dextro and levo, respectively), depending on the position of the atoms surrounding the α-carbon.

However, alanine, as with most amino acids, is found mostly in the L form, since it is the form that enzymes insert during protein synthesis.

This amino acid can also be found as β-alanine, in which the amino group is attached to its β-carbon, that is, to the first carbon of its side chain.

Β-Alanine is found in pantothenic acid (vitamin B5) and in some natural peptides. D-Alanine is found in some polypeptides that are part of the walls of some bacterial cells.

Group R (methyl, CH

The methyl group of the alanine side chain is a saturated hydrocarbon that gives the nonpolar hydrophobic characteristic to this amino acid. This characteristic of alanine is common with the other amino acids of this group such as glycine, valine, leucine and isoleucine.

The amino acids that make up the group of aliphatics are chemically neutral amino acids and play a very important role in the formation and maintenance of the three-dimensional structure of proteins since they have the tendency to react with each other excluding water.

These amino acids, including alanine, contain the same number of ionizable groups with opposite charges, so they do not have a net charge and are called "zwitterions."

Features

Like most of the known amino acids, alanine is used in the synthesis of peptides and proteins in general, and participates in the establishment of the polypeptide structure and in the tertiary structure of some proteins.

Another important function of alanine is to participate indirectly in the control of glycemia:

It can give rise to pyruvate and vice versa, it can also reach the liver and become glucose through gluconeogenesis to be released into the circulation or to be used in the synthesis of glycogen, as necessary.

Alanine participates as an ammonium transporter from the muscle to the liver, since it can be synthesized by amination from pyruvate, transported to the liver and there be transformed by transamination.

This occurs concomitantly with the transformation of α-ketoglutarate to glutamate, which can enter the urea cycle and convert back to pyruvate.

Other functions

This amino acid is essential for the synthesis of tryptophan and pyridoxine. Although chemically poorly reactive, alanine may have substrate recognition and enzyme regulation functions.

One of the functions of β-alanine is as a dietary supplement, as it is used as an ergogenic exercise aid. The ingestion of β-alanine increases the concentration of carnosine (a dipeptide formed by β-alanine and histidine) in skeletal muscle, acting as a “buffer”.

Normally, carnosine does not contribute significantly to the total buffer capacity of the muscle cell and this is due to its low concentration. The administration of β-alanine increases this concentration and therefore the buffer capacity, thus improving endurance by reducing fatigue.

Biosynthesis

The most important synthesis of alanine in the human body occurs by a reductive amination of pyruvic acid. This reaction requires a single enzymatic step.

Pyruvate provides the carbon skeleton and glutamate provides the amino group that is transferred to pyruvate. The enzyme that catalyzes this reversible reaction is alanine transaminase.

As a result of this reaction, alanine and α-ketoglutarate are produced. Alanine can then be present in gluconeogenesis, in glycolysis and in the Krebs cycle.

Another source of alanine comes from the breakdown of tryptophan to acetyl-CoA. In this route, when the enzyme kynureninase hydrolyzes 3-hydroxy kynurenine, 3-hydroxy anthranilate and alanine are formed. Alanine is released and 3-hydroxy anthranilate follows the metabolic pathway.

The degradation of uracil is another source of alanine. In this case, β-alanine is produced, which can follow several metabolic pathways, one of which is to become acetyl-CoA.

Degradation

General process of amino acid degradation

Amino acids are not stored like carbohydrates and fats, so those that are released during protein degradation must be reused for the synthesis of new proteins and nucleotides.

On the other hand, amino acids can be degraded and their carbon skeletons can be used in catabolic or anabolic reactions.

When amino acids are degraded, excess nitrogen forms ammonia, which is a toxic substance that must be eliminated and the first step in amino acid degradation is the elimination of nitrogen.

In mammals, this degradation occurs in the liver; there, any amino acid that is in excess and cannot be used is degraded.

Alanine degradation

The degradation of alanine occurs by the conversion of alanine to pyruvate. This reaction is catalyzed by alanine transaminase and requires the presence of α-ketoglutarate as an acceptor of the amino group and the subsequent formation of glutamate; it is a reversible reaction.

These reactions of the formation of alanine from pyruvate and the breakdown of alanine to form pyruvate are part of a cycle involving skeletal muscle and liver.

The liver supplies glucose to the muscle and the muscle, through glycolysis, converts glucose into pyruvate in order to generate ATP; This pyruvate can enter the synthesis of alanine, which can be released into the bloodstream and returns to the liver which converts it back to pyruvate, which enters gluconeogenesis to form glucose.

If necessary, the cycle is repeated. In the liver, the production of pyruvate from alanine generates ammonium ions that bind to glutamine and glutamate and these enter the urea cycle. Then the urea is eliminated in the urine.

Alanine, glycine, cysteine, serine, and threonine are glucogenic amino acids since their degradation can give rise to pyruvate, α-ketoglutarate, succinyl-CoA, fumarate or oxaloacetate, all gluconeogenic precursors of glucose.

Alanine rich foods

The main sources of amino acids are lean meats, fish, shellfish, eggs, and dairy products, however, alanine is also found in many plant-based foods. Examples of foods rich in alanine are:

- Meats such as beef, pork, sheep, chicken, turkey, rabbit, fish; eggs, milk and derivatives.

- Nuts such as hazelnuts, walnuts, chestnuts, almonds and peanuts are sources of alanine.

- Coconut, avocado, asparagus, eggplant, cassava or cassava, beet, carrot and sweet potato.

- Legumes such as corn, beans and peas.

- Cereals such as rice, rye, wheat, cocoa, oats and rye.

References

1. Caruso, J., Charles, J., Unruh, K., Giebel, R., Learmonth, L., & Potter, W. (2012). Ergogenic effects of β-alanine and carnosine: Proposed future research to quantify their efficacy. Nutrients, 4 (7), 585–601.
2. Gille, C., Bölling, C., Hoppe, A., Bulik, S., Hoffmann, S., Hübner, K.,… Holzhütter, HG (2010). HepatoNet1: A comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology. Molecular Systems Biology, 6 (411), 1–13.
3. Mathews, C., van Holde, K., & Ahern, K. (2000). Biochemistry (3rd ed.). San Francisco, California: Pearson.
4. Murray, R., Bender, D., Botham, K., Kennelly, P., Rodwell, V., & Weil, P. (2009). Harper's Illustrated Biochemistry (28th ed.). McGraw-Hill Medical.
5. Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.).