Did you know that the average human adult requires around 1.0 to 1.2 grams of protein per kilogram of body weight, depending on body composition? Because proteins are responsible for many life-sustaining functions, protein undernutrition can lead to stunting, physical weakness, and impaired immunity.
Our body digests and utilizes proteins in the form of amino acids. It also synthesizes proteins and nitrogen-containing compounds like hormones and nucleotide bases using amino acids present in the body. Such processes are collectively referred to as amino acid metabolism.
- First, we will look at what proteins are.
- Then, we will dive into the definition of amino acid metabolism.
- After, we will learn about how the function of enzymes in amino acid metabolism.
- Lastly, we will explore some amino acid metabolism disorders.
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.
An amino acid is a group of organic molecules with an amino group (-NH2), a carboxyl group (-COOH), and a side chain (called R group) unique to every amino acid. Each amino acid molecule has a central carbon C atom to which the amino and carboxyl groups are attached.
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.
Proteins are amino acid chains connected by peptide bonds.
- A peptide bond is an amide bond formed between amino acids by the condensation of -NH2 and -COOH, releasing H2O.
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 acid metabolism refers to the sum of all chemical reactions in which amino acids are broken down and synthesized for vital processes in the body.
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.
Table 1. Essential and Non-essential amino acids in humans |
|---|
Essential amino acids | Non-essential amino acids |
Histidine* Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine | Alanine Arginine (essential for children and adolescents) Asparagine Aspartic acid Cysteine Glutamic acid Glutamine Glycine Proline Serine Tyrosine (produced from phenylalanine) |
*Although histidine is on the list of essential amino acids, some textbooks consider it to be conditionally essential, as it is only fully essential in childhood.
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.
The replacement of older proteins as they degrade within the cell is referred to as protein turnover.
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).
Unlike fats and carbohydrates, there is no dedicated storage of proteins and amino acids in the human body. If not used for biological processes, excess amino acids in the body are typically degraded, and the nitrogen is expelled as urea. However, the body can conserve protein when in a state of nutrient deficiency or withdrawal.
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.
In transamination, a nitrogen-containing amino group (from an amino acid) gets transferred to an acceptor keto acid (an alpha-ketoglutarate), forming an amino acid glutamate and a keto acid pyruvate.
- A keto acid is an organic compound with a carboxylic acid (-COOH) and a ketone group (a carbonyl group C=O bonded to other carbon atoms or hydrocarbon radicals).
An example of a transamination reaction converting alanine into glutamic acid. The enzyme used in this reaction is called alanine transaminase (ALT).
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.
Table 2. Amino acids classification based on their degradation pathways |
|---|
| Glucogenic | Both glucogenic and ketogenic | Ketogenic |
| AlanineArginineAsparagineAspartateCysteineGlutamateGlutamineGlycineHistidineMethionineProlineSerineThreonineValine | IsoleucinePhenylalanineTryptophanTyrosine | LeucineLysine |
Amino acid metabolism enzymes
Now, let's talk about the role of enzymes in the metabolism of amino acids.
Enzymes are special types of proteins that catalyze or accelerate biochemical reactions without getting used up in the reaction.
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.
Problems with enzyme pathways involved in amino acid metabolism can lead to amino acid disorders.
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.
Because of this risk, babies born in US hospitals are typically screened for PKU, allowing for early detection and treatment.
Those with PKU are typically required to have a low-protein diet. Newborns are prescribed a special formula, while older children and adults are recommended a diet that consists mostly of fruits, vegetables, and low-protein bread, pasta, and cereals.
Most babies that get on this strict diet soon after they are born eventually develop normally and show no symptoms of PKU.
Argininosuccinic Aciduria (ASA)
Argininosuccinic aciduria is a disorder where the enzyme argininosuccinate lyase is dysfunctional or missing.
Argininosuccinate lyase is responsible for starting the reaction in which the amino acid arginine is synthesized from argininosuccinate, a molecule that carries the nitrogenous waste collected in the urea cycle. Arginine breaks down into ornithine, which initiates the urea cycle, and urea, which is excreted.
Because the enzyme argininosuccinate lyase (ASL) is dysfunctional or missing, arginine is not synthesized, and nitrogen is not expelled. Excess nitrogen can then accumulate in the blood in the form of ammonia, which can be toxic at high levels.
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.
Fortunately, most cases of ASA can be detected shortly after birth by screening.
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.
Amino Acid Metabolism - Key takeaways
- Amino acid metabolism refers to the sum of all chemical reactions in which amino acid is broken down and synthesized for vital processes in the body.
- Non-essential amino acids can be synthesized by the body while essential amino acids must be taken in through food.
- Free amino acids can be used in synthesizing protein and other nitrogen-containing compounds.
- Amino acid carbon skeletons can be processed and used as an energy source or used for glucose synthesis during hypoglycemia.
- The nitrogen in amino acid carbon skeletons that are oxidized for energy or converted to glucose are then excreted in the urine in the form of urea. Excess amino acid is also expelled as urea.
References
- Michael Reddy, Amino Acid | Definition, Structure, and Facts, Encyclopedia Britannica, 22 Aug. 2022.
- Kevin Ahern and Indira Rajagopal, 7.7: Amino Acid Metabolism, Biology LibreTexts, 26 Feb. 2016.
- McMurry et al, 25.2: Amino Acid Metabolism - an Overview, Chemistry LibreTexts, 5 Aug. 2017.
- University of Arizona Department of Molecular & Cellular Biology, Amino Acids, Accessed 14 Oct. 2022.
- NYU School of Medicine, Amino Acid Metabolism: Introduction, Accessed 14 Oct. 2022.
- University of Nevada, Reno School of Medicine, Amino Acid Metabolic Disorders, Accessed 14 Oct. 2022.
- MedlinePlus, Phenylketonuria, 22 Nov. 2016.
- MedlinePlus Genetics, Argininosuccinic Aciduria, 1 Mar. 2020.
- Gerald Litwack, Chapter 13 - Metabolism of Amino Acids, Human Biochemistry, 2018.
- P. Newsholme, L. Stenson, M. Sulvucci, R. Sumayao, M. Krause, 1.02 - Amino Acid Metabolism, 2011.
- Guoyao Wu, Dietary Protein Intake and Human Health, PubMed, 1 Mar. 2016.
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