Introduction:
In the adult human body, only about 20% of the amino acids released from protein breakdown are catabolized to produce energy, while the remaining 80% are reused for the synthesis of new proteins. However, any excess amino acids consumed through the diet are also broken down for energy, as amino acids cannot be stored in the body.
Under normal physiological conditions, amino acids contribute around 5–10% of total body energy. The rate of amino acid catabolism increases significantly during starvation, uncontrolled diabetes mellitus, and a high-protein diet.
Besides energy production, amino acids also serve as precursors for the synthesis of creatine, hormones, glutathione, purines, and pyrimidines.
Stages of Amino Acid Catabolism
The breakdown of amino acids occurs in two main stages:
- Removal of the amino group — The α-amino group is released as ammonia, which is then converted to urea for excretion.
- Utilization of the carbon skeleton — The remaining carbon skeleton is converted into intermediates such as acetyl-CoA or TCA cycle compounds for energy production, glucose formation, or ketone body synthesis.
Deamination of Amino Acids
Deamination is the process by which the amino group (-NH₂) is removed from the amino acid. This is the first step in amino acid degradation, and it can occur in several ways:
- Transamination followed by oxidative deamination
- Direct oxidative deamination
- Non-oxidative deamination
1. Transamination Followed by Oxidative Deamination
a) Transamination
Transamination is the reversible transfer of an amino group from an amino acid to a keto acid, usually α-ketoglutarate. This process is catalyzed by enzymes called transaminases (aminotransferases), which require pyridoxal phosphate (vitamin B₆) as a coenzyme.
Example: Aspartate transaminase (AST) transfers the amino group from aspartate to α-ketoglutarate, forming oxaloacetate and glutamate.
Alanine transaminase (ALT) is another important enzyme that transfers the amino group from alanine to α-ketoglutarate, producing pyruvate and glutamate.
These reactions primarily occur in the liver, kidney, and muscle tissues, within both the mitochondria and cytosol.
Overall, glutamate acts as a central collector of amino groups from various amino acids during transamination.
b) Oxidative Deamination
The amino group collected in the form of glutamate is released as free ammonia (NH₃) through the process of oxidative deamination. This reaction is catalyzed by the enzyme glutamate dehydrogenase, which uses either NAD⁺ or NADP⁺ as a coenzyme.
Reaction: Glutamate + NAD⁺ ⇌ α-Ketoglutarate + NH₃ + NADH + H⁺
This enzyme is present in both the mitochondria and cytosol of liver cells and is regulated allosterically — ATP and GTP inhibit its activity, while ADP and GDP activate it.
Thus, the combined action of transaminases and glutamate dehydrogenase results in the efficient removal of amino groups from most amino acids as ammonia.
2. Direct Oxidative Deamination
Some amino acids can undergo direct oxidative deamination without prior transamination. This reaction is catalyzed by amino acid oxidases, which use flavin coenzymes (FAD or FMN) instead of NAD⁺.
- D-Amino Acid Oxidase (DAAO): Found mainly in the liver and kidney; it uses FAD as a cofactor and acts on D-amino acids such as glycine.
- L-Amino Acid Oxidase (LAAO): Found in the liver and kidney; uses FMN as a coenzyme but has low activity in humans.
The reaction occurs in two steps:
- Oxidation of the amino acid to an imino acid, reducing FAD or FMN.
- Hydrolytic deamination of the imino acid to produce the corresponding α-keto acid and ammonia.
3. Non-Oxidative Deamination
In this type of reaction, ammonia is released from amino acids without the involvement of oxygen. The enzymes involved require pyridoxal phosphate (vitamin B₆) as a cofactor.
Examples:
- Serine dehydratase: Catalyzes non-oxidative deamination of serine to form pyruvate. The process involves dehydration to dehydroalanine followed by hydrolysis with ammonia release.
- Threonine dehydratase: Converts threonine to α-ketobutyrate and ammonia.
- Cysteine desulfhydrase (in bacteria): Converts cysteine to pyruvate by removing sulfur and ammonia.
These enzymes play a role in nitrogen metabolism and the removal of amide nitrogen from amino acids such as glutamine and asparagine.
Decarboxylation of Amino Acids
Decarboxylation refers to the removal of a carboxyl group (-COOH) from an amino acid, producing the corresponding amine and releasing carbon dioxide (CO₂). The reaction requires the coenzyme pyridoxal phosphate (vitamin B₆) and is catalyzed by amino acid decarboxylases.
These enzymes are found in various tissues such as the liver, kidney, spleen, intestine, brain, and lungs. The resulting biogenic amines have important physiological roles.
Examples:
- Histidine → Histamine (by histidine decarboxylase)
- Tryptophan → Tryptamine (by tryptophan decarboxylase)
- Tyrosine → Tyramine (by tyrosine decarboxylase)
These biogenic amines act as neurotransmitters, hormones, or signaling molecules in various biological processes.
Detailed Notes:
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