Amino acids are degraded through a multi-step process, primarily involving the removal of the amino group followed by the metabolism of the remaining carbon skeleton.
Here's a breakdown of the amino acid degradation process:
1. Removal of the α-Amino Group:
This is the first crucial step. The amino group, which contains nitrogen, is removed, as it is toxic in high concentrations. This process largely occurs in the liver. There are several mechanisms for this:
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Transamination: This is often the first step, where the amino group is transferred from the amino acid to α-ketoglutarate, forming glutamate. This reaction is catalyzed by aminotransferases (or transaminases), which require pyridoxal phosphate (PLP), a derivative of vitamin B6, as a coenzyme. This essentially concentrates the amino groups onto one molecule, glutamate.
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Oxidative Deamination: Glutamate, now carrying the amino group from other amino acids, undergoes oxidative deamination in the mitochondria of liver cells. This reaction is catalyzed by glutamate dehydrogenase, releasing free ammonia (NH3) and regenerating α-ketoglutarate, which can then participate in further transamination reactions. NAD+ or NADP+ act as coenzymes.
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Direct Deamination: Some amino acids, like serine and threonine, can be directly deaminated by enzymes called dehydratases. These enzymes remove water (dehydration) and ammonia, forming an unsaturated intermediate that is then converted to an α-keto acid.
2. Urea Cycle (Ammonia Disposal):
The free ammonia produced is highly toxic. It is converted into urea, a less toxic compound, through the urea cycle, which occurs primarily in the liver. Urea is then transported to the kidneys and excreted in urine.
3. Metabolism of the Carbon Skeleton:
After the amino group is removed, the remaining carbon skeleton (α-keto acid) is metabolized to form intermediates that can enter central metabolic pathways. These intermediates include:
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Pyruvate: Alanine, serine, cysteine, glycine, and threonine are converted to pyruvate.
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Acetyl CoA: Isoleucine, leucine, tryptophan, and lysine are converted to acetyl CoA.
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Acetoacetyl CoA: Leucine, lysine, phenylalanine, tyrosine, and tryptophan are converted to acetoacetyl CoA.
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Succinyl CoA: Isoleucine, methionine, threonine, and valine are converted to succinyl CoA.
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Fumarate: Phenylalanine and tyrosine are converted to fumarate.
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Oxaloacetate: Aspartate and asparagine are converted to oxaloacetate.
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α-Ketoglutarate: Glutamate, glutamine, proline, arginine, and histidine are converted to α-ketoglutarate.
4. Entry into Central Metabolic Pathways:
The products of carbon skeleton metabolism (pyruvate, acetyl CoA, acetoacetyl CoA, succinyl CoA, fumarate, oxaloacetate, and α-ketoglutarate) can then be used in:
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Gluconeogenesis: The synthesis of glucose (glucogenic amino acids). Amino acids that are converted into pyruvate, oxaloacetate, fumarate, succinyl CoA, or α-ketoglutarate are glucogenic.
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Ketogenesis: The synthesis of ketone bodies (ketogenic amino acids). Amino acids that are converted into acetyl CoA or acetoacetyl CoA are ketogenic. Some amino acids are both glucogenic and ketogenic.
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Energy Production (TCA cycle): All of these intermediates feed into the citric acid cycle (TCA cycle) for the production of energy (ATP).
Summary Table:
| Step | Description | Key Enzymes | Location |
|---|---|---|---|
| Transamination | Transfer of the amino group from an amino acid to α-ketoglutarate. | Aminotransferases (Transaminases) | Cytosol/Mitochondria |
| Oxidative Deamination | Removal of ammonia from glutamate, regenerating α-ketoglutarate. | Glutamate dehydrogenase | Mitochondria |
| Urea Cycle | Conversion of toxic ammonia into urea for excretion. | A series of enzymes, including carbamoyl phosphate synthetase I, ornithine transcarbamoylase, etc. | Cytosol/Mitochondria |
| Carbon Skeleton Metabolism | Conversion of the carbon skeleton to metabolic intermediates. | Variety of enzymes specific to each amino acid, including oxidoreductases, lyases, isomerases, decarboxylases | Cytosol/Mitochondria |
| Entry into Metabolism | Metabolic intermediates from amino acid degradation enter gluconeogenesis, ketogenesis, or the TCA cycle. | Enzymes specific to each pathway | Cytosol/Mitochondria |
In summary, amino acid degradation is a complex process that involves the removal of the amino group (leading to urea formation for excretion) and the conversion of the remaining carbon skeleton into intermediates that can be used for energy production, glucose synthesis, or ketone body formation.
