Amino Acid Metabolism

Protein and amino acid metabolism

Alongside carbohydrates, fats, and nucleic acids, proteins are one of the organic molecules that make up most life forms. They are responsible for catalyzing most of the chemical reactions that take place in the cell. They provide cells with a lot of their structural components and aid in binding cells into tissues.

Protein is typically digested and absorbed in the form of amino acids.

There are 20 different types of amino acids that constitute proteins, and the sequence of amino acids determines the structure and properties of the resulting protein.

Amino acid metabolism definition

Recall that metabolism refers to the chemical reactions that take place in living organisms to provide energy for life-sustaining processes and to synthesize new organic materials. Now, let's look at the definition of amino acid metabolism.

Amino acids can be divided into two types: essential and non-essential amino acids.

• Essential amino acids are amino acids necessary for an organism's survival. Since we cannot synthesize these essential amino acids by ourselves, we must obtain them from our diets.

• Non-essential amino acids are amino acids that can be synthesized by the body.

The table below shows the essential and non-essential amino acids in adult humans.

Now, did you know that not all the amino acids required for the body's biological processes need to be ingested through food? After completing their lifespan, proteins already present in the metabolism can be recycled!

Cellular amino acid pools are constantly being partially drained and refilled as the body synthesizes and degrades proteins.

In a healthy adult human, around 300-600g of protein are broken down and synthesized each day. Protein turnover allows not only for variations in the amount of proteins synthesized in accordance with the physiological needs of the body but also for the removal of dysfunctional proteins.

Depending on the specific role they perform, proteins have different rates of turnover. For example, enzymatic proteins tend to have a shorter life span to better adapt to the body's metabolic needs whereas, structural proteins typically have longer half-lives (in the range of years).

Once proteins have been broken down, free amino acids combine with the non-essential amino acids produced in the liver and those recycled from the body’s own proteins, constituting the amino acid pool that is accessible for metabolic processes.

Free amino acids can be used in two major ways:

• They can be used in synthesizing protein and other nitrogen-containing compounds like nucleotide bases, neurotransmitters, and hormones.

• The carbon skeletons of amino acids can also be oxidized and then utilized as an energy source or used for glucose synthesis during hypoglycemia (a state of having low glucose levels in the blood).

Metabolic Classification of Amino Acids

Amino acid metabolism starts with a protein being broken down into amino acids, which are the building blocks for protein synthesis. Then, these amino acids can undergo an important reaction involved in amino acid metabolism called transamination. The major organ responsible for transamination reactions is the liver.

After, glutamic acid undergoes a process called oxidative deamination, where the amino group gets removed, and the amino acid gets utilized for energy. This process produces ammonia, which is converted into urea for renal excretion.

Amino acids can also be classified based on the pathways involved in their degradation:

• Glucogenic amino acids are those whose carbon skeletons are converted into pyruvate or another citric acid cycle (TCA cycle) intermediate.
• Ketogenic amino acids are those whose carbon skeletons are converted into acetyl-CoA or acetoacetyl-CoA, both of which are used to produce ketone bodies. Leucine and lysine are the only amino acids that are purely ketogenic. Their degradation yields acetyl-CoA and acetoacetyl-CoA.

Amino acid metabolism can also lead to the formation of intermediates that belong to both categories and are therefore called both glucogenic and ketogenic. For example, the breakdown of isoleucine yields both acetyl-CoA and succinyl-CoA.

The amino acids are classified as glucogenic, ketogenic, or both in Table 2 below.

Amino acid metabolism enzymes

Now, let's talk about the role of enzymes in the metabolism of amino acids.

A chain of enzymes can catalyze a series of reactions called pathways to synthesize or breakdown complex biological molecules.

Enzymes are involved in both the synthesis and degradation of amino acids. It is also involved in the coordination of the reactions involved in protein synthesis and in the production of urea.

Amino acid metabolism disorders

Amino Acid Disorders (AAs) are diseases brought on by dysfunctional enzymes. People with amino acid disorders have trouble breaking down some amino acids because of missing or inactive enzymes. These amino acids, as well as other toxic substances, then accumulate in the body and cause issues.

Amino acid metabolism disorder treatment

Let’s go through some examples of amino acid disorders and how they are typically screened and treated.

Phenylketonuria (PKU)

Phenylketonuria is a hereditary amino acid metabolism disorder where the body cannot process the amino acid phenylalanine to make tyrosine due to a mutation in the enzyme phenylalanine hydroxylase. When phenylalanine levels are too high, the brain can be damaged and cause severe intellectual disability.

Argininosuccinic Aciduria (ASA)

Argininosuccinic aciduria is a disorder where the enzyme argininosuccinate lyase is dysfunctional or missing.

Symptoms of ASA include drowsiness, little appetite, breathing problems, seizures, and unusual body movements.

This disease is fatal, so babies with ASA who are left untreated can die within the first few weeks of life.

Treatment for ASA can range from the recommendation of low-protein, nitrite-rich foods to the intake of large amounts of exogenous arginine, which will promote the synthesis of argininosuccinate.