What happens when amino acids are broken down? The metabolic process explained

Did you know that in a healthy human, the body cycles approximately 300 grams of protein every day? This constant turnover of building blocks necessitates a precise process for dealing with surplus material. When amino acids are broken down, the body carefully recycles and eliminates their components for fuel, synthesis, and waste removal.

Quick Summary

Amino acid breakdown starts with removing the amino group, forming toxic ammonia that is converted to urea in the liver. The leftover carbon skeletons are repurposed for energy, glucose, or ketone body production.

Key Points

• Two-part Breakdown: When amino acids are broken down, they are separated into a nitrogen-containing amino group and a carbon skeleton.

• Nitrogen Detoxification: The highly toxic ammonia released from the amino group is converted into non-toxic urea in the liver via the urea cycle, and then excreted.

• Carbon Skeleton Fate: The remaining carbon skeleton is recycled and can be used for energy production, converted into glucose, or synthesized into ketone bodies.

• Glucogenic and Ketogenic Categories: Amino acids are classified based on whether their carbon skeletons can be converted into glucose (glucogenic), ketone bodies (ketogenic), or both.

• Energy Source during Fasting: In times of low carbohydrate intake, such as prolonged fasting, the body uses amino acids as a critical source for glucose production (glucogenic) and ketone body synthesis (ketogenic).

• Adaptable Metabolism: The body's ability to repurpose amino acid components demonstrates a flexible metabolic strategy for maintaining energy homeostasis under various nutritional conditions.

The Initial Steps: Separation of Amino and Keto Groups

When an excess of amino acids exists beyond the body’s need for protein synthesis, they cannot be stored. The initial step in their breakdown is the removal of the nitrogen-containing amino group ($$-NH_2$$). This is a critical process because the resulting nitrogenous waste can be highly toxic if allowed to accumulate. This process primarily occurs in the liver, though other tissues like the kidneys and muscles also contribute.

Transamination: The First Nitrogen Transfer

Transamination is the most common initial reaction in amino acid catabolism, involving the transfer of the amino group from an amino acid to an α-keto acid. This is catalyzed by enzymes called transaminases, which require pyridoxal phosphate (a derivative of vitamin B6) as a coenzyme. In many of these reactions, the amino group is transferred to α-ketoglutarate, converting it into glutamate, a central amino acid in nitrogen metabolism. The original amino acid is left behind as its corresponding α-keto acid, or carbon skeleton.

Oxidative Deamination: Releasing Ammonia

Once concentrated into glutamate via transamination, the nitrogen can be released as ammonia ($$NH_3$$) through oxidative deamination. This reaction is catalyzed by the enzyme glutamate dehydrogenase, primarily in the liver mitochondria. Glutamate is converted back into α-ketoglutarate, and the newly freed ammonia is a potent toxin that must be detoxified immediately.

Detoxifying Nitrogen: The Urea Cycle

The urea cycle is a series of biochemical reactions that convert the highly toxic ammonia into the much less toxic compound urea. This cycle takes place predominantly in the liver and, to a lesser extent, in the kidneys. The urea produced is then transported through the bloodstream to the kidneys and excreted in the urine.

Steps in the Urea Cycle

1. Entry into the Cycle: Ammonia combines with bicarbonate and ATP in the mitochondria to form carbamoyl phosphate.
2. Conversion to Citrulline: Carbamoyl phosphate combines with ornithine to form citrulline. Ornithine is recycled at the end of the process, much like oxaloacetate in the Krebs cycle.
3. Formation of Argininosuccinate: Citrulline is transported to the cytosol and reacts with aspartate to form argininosuccinate.
4. Cleavage to Arginine and Fumarate: Argininosuccinate is cleaved, producing arginine and fumarate. Fumarate links the urea cycle to the citric acid cycle.
5. Release of Urea: Arginine is hydrolyzed, releasing a molecule of urea and regenerating ornithine to continue the cycle.

The Fate of the Carbon Skeleton

After the amino group has been removed, the remaining carbon skeleton (the α-keto acid) can follow several metabolic paths depending on the body's needs and the specific amino acid. These skeletons are ultimately channeled into intermediates of the central metabolic pathways, such as glycolysis or the citric acid cycle.

Glucogenic vs. Ketogenic Amino Acids

Amino acids are categorized based on what their carbon skeletons are converted into.

• Glucogenic Amino Acids: These are broken down into pyruvate or one of the citric acid cycle intermediates (e.g., α-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate). These intermediates can be used for gluconeogenesis, the synthesis of new glucose. This is particularly important during fasting or starvation to maintain blood sugar levels for the brain and other tissues.
• Ketogenic Amino Acids: These are converted into acetyl-CoA or acetoacetyl-CoA. These molecules cannot be used to produce new glucose but can be used for the synthesis of ketone bodies, which serve as an alternative energy source during prolonged fasting or carbohydrate restriction. Only two amino acids, leucine and lysine, are exclusively ketogenic.

Metabolic Destinations of Carbon Skeletons

Each amino acid's carbon skeleton follows a unique set of reactions to enter a central metabolic pathway.

• Pyruvate: The carbon skeletons of alanine, cysteine, glycine, serine, and threonine enter metabolism via pyruvate.
• Oxaloacetate: Aspartate and asparagine are converted to oxaloacetate.
• α-Ketoglutarate: Glutamine, proline, arginine, and histidine are all broken down into glutamate and then into α-ketoglutarate.
• Succinyl-CoA: Methionine, valine, and isoleucine are converted into succinyl-CoA.
• Fumarate: Phenylalanine and tyrosine contribute to fumarate formation.
• Acetyl-CoA/Acetoacetate: Leucine and lysine are exclusively ketogenic, breaking down into acetyl-CoA and acetoacetate.

Comparison of Glucogenic vs. Ketogenic Amino Acids

Feature	Glucogenic Amino Acids	Ketogenic Amino Acids
Final Products (Carbon Skeleton)	Pyruvate, or intermediates of the citric acid cycle (e.g., oxaloacetate, α-ketoglutarate)	Acetyl-CoA or acetoacetyl-CoA
Glucose Production	Can be converted into glucose via gluconeogenesis.	Cannot be converted into glucose.
Energy Source	Primarily used for energy via the citric acid cycle, especially in muscle and liver cells.	Used to produce ketone bodies, an alternative fuel for tissues like the brain during fasting.
Example Amino Acids	Alanine, Glycine, Serine, Aspartate, Asparagine, Glutamate, Glutamine, Arginine, Proline, Histidine, Cysteine, Methionine, Valine.	Leucine and Lysine (exclusively).
Dual Function	Some amino acids like isoleucine, phenylalanine, threonine, tryptophan, and tyrosine are both glucogenic and ketogenic.	A small number of amino acids have dual functions, as listed opposite.

Conclusion: A Highly Coordinated Process

The breakdown of amino acids is a multi-step, highly regulated metabolic process that is essential for maintaining a healthy and balanced internal environment. The body efficiently separates the nitrogenous waste from the carbon-based components. The toxic nitrogen is safely converted into urea and excreted, while the versatile carbon skeletons are repurposed for critical functions, including energy production through the citric acid cycle, glucose synthesis via gluconeogenesis, or the creation of ketone bodies during periods of low glucose availability. This intricate system highlights the body’s remarkable ability to adapt its metabolic strategies based on nutritional status and energy demands.

For more detailed information on metabolic pathways, please visit Chemistry LibreTexts.

Frequently Asked Questions

What is the very first step in breaking down amino acids?

The initial step is the separation of the amino group from the carbon skeleton. This typically occurs through transamination, where the amino group is transferred to an α-keto acid.

Why does the body need to get rid of the nitrogen from amino acids?

The nitrogen is converted into ammonia, which is extremely toxic to cells, especially those in the brain. The body must quickly convert this into a less harmful substance, urea, to prevent a fatal build-up.

Where does the urea cycle take place?

The urea cycle, which detoxifies ammonia into urea, occurs primarily in the cells of the liver. The kidneys also participate to a lesser extent.

What is the difference between glucogenic and ketogenic amino acids?

Glucogenic amino acids can be converted into glucose, while ketogenic amino acids are converted into ketone bodies. Some amino acids are both.

Can the body produce glucose from all amino acids?

No. Only the glucogenic amino acids can be converted to glucose. The strictly ketogenic amino acids, leucine and lysine, cannot enter the gluconeogenesis pathway.

What role do ketone bodies play in metabolism?

Ketone bodies, produced from ketogenic amino acids and fatty acids, serve as an alternative fuel source for the body. They are especially important for the brain during prolonged fasting or very low-carb diets.

How do amino acids provide energy for the body?

After the amino group is removed, the remaining carbon skeletons are converted into intermediates that can enter the citric acid cycle. This process generates ATP, providing energy for the cell.