glutamate catabolic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the breakdown of glutamate, the anion of 2-aminopentanedioic acid. [GOC:go_curators]

Glutamate catabolism is a vital metabolic pathway that plays a crucial role in the breakdown of the neurotransmitter glutamate, ultimately yielding energy in the form of ATP. This process is tightly regulated and occurs primarily in the liver and kidneys, but also in other tissues. The primary catabolic pathway for glutamate is the **glutamate dehydrogenase (GDH) pathway**, which involves the following steps:

1. **Transamination:** Glutamate can be transaminated by various aminotransferases, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), to form alpha-ketoglutarate. This process is reversible and plays a key role in amino acid metabolism.

2. **Oxidative Deamination:** Glutamate is deaminated by glutamate dehydrogenase (GDH), a mitochondrial enzyme, to produce alpha-ketoglutarate and ammonia. This step is irreversible and requires NAD+ as a cofactor.

3. **Tricarboxylic Acid (TCA) Cycle:** Alpha-ketoglutarate enters the TCA cycle, a series of enzymatic reactions that generate ATP through oxidative phosphorylation.

**Additional pathways:**

- **Glutaminase:** Glutamine, an amide derivative of glutamate, can be hydrolyzed by glutaminase to release glutamate and ammonia. This pathway is important for glutamate homeostasis and ammonia detoxification.

- **Gamma-glutamyl cycle:** This cycle is involved in the synthesis and degradation of glutathione, a tripeptide antioxidant.

**Regulation:**

Glutamate catabolism is tightly regulated by several factors, including:

- **GDH activity:** GDH activity is regulated by allosteric effectors, such as ADP and GTP.
- **Hormonal control:** Insulin stimulates glutamate catabolism, while glucagon inhibits it.
- **Cellular energy status:** High levels of ATP inhibit GDH activity, while low levels of ATP activate it.

**Significance:**

Glutamate catabolism is crucial for:

- **Energy production:** Glutamate is a major energy source for many tissues, particularly the brain.
- **Ammonia detoxification:** The ammonia produced during glutamate catabolism is detoxified in the liver and excreted in the urine.
- **Neurotransmitter homeostasis:** Glutamate catabolism helps regulate the levels of glutamate in the brain, which is essential for neuronal function.

**Disorders:**

Defects in glutamate catabolism can lead to several disorders, including:

- **Hyperammonemia:** Excessive accumulation of ammonia in the blood, due to impaired ammonia detoxification.
- **Neurological disorders:** Deficiencies in glutamate metabolism can affect brain function and lead to neurological disorders.

**Therapeutic applications:**

Glutamate catabolism is targeted by several therapeutic strategies, including:

- **Anticonvulsants:** Some anticonvulsants work by inhibiting glutamate release or enhancing glutamate catabolism.
- **Neuroprotective agents:** Compounds that enhance glutamate catabolism may have neuroprotective effects in neurological disorders.

**Overall, glutamate catabolism is a complex and vital metabolic pathway that plays a critical role in energy production, ammonia detoxification, neurotransmitter homeostasis, and overall cellular function.**'
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Proteins (2)

Compounds (4)