Glutamate dehydrogenase (nad(p)+)

Glutamate dehydrogenase (NAD(P)+) is an enzyme that plays a crucial role in nitrogen metabolism and energy production in living organisms. This enzyme catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate and ammonia, while reducing NAD+ or NADP+ to NADH or NADPH, respectively. This reaction is fundamental in the process of amino acid catabolism, which contributes to the urea cycle and the citric acid cycle (TCA cycle), linking nitrogen and carbon metabolism pathways.

Function

Glutamate dehydrogenase (NAD(P)+) is located in the mitochondria of cells and is involved in the amino acid metabolism, playing a key role in the interconversion of amino acids and energy. By catalyzing the deamination of glutamate, it provides alpha-ketoglutarate, a critical intermediate in the citric acid cycle, thus contributing to energy production. Additionally, the enzyme facilitates the removal of excess nitrogen from the body by producing ammonia, which is eventually converted to urea and excreted.

Structure

The enzyme is known to exist in multiple forms, depending on the organism. In humans, it is a hexameric protein composed of six identical subunits. Each subunit binds to a molecule of NAD+ or NADP+, which are essential cofactors for the enzyme's activity. The structure of glutamate dehydrogenase is crucial for its function, as it allows for the binding of substrates and cofactors, and the proper orientation of the enzyme's active site for catalysis.

Regulation

The activity of glutamate dehydrogenase (NAD(P)+) is tightly regulated by various metabolites, ensuring that it functions appropriately in response to the metabolic needs of the cell. It is allosterically activated by ADP and GDP, which indicate a high demand for energy, and inhibited by ATP and GTP, signaling an abundance of energy. This regulation ensures that the enzyme's activity is aligned with the cell's energy status and metabolic requirements.

Clinical Significance

Alterations in the activity of glutamate dehydrogenase can have significant implications for human health. For instance, hyperactivity of this enzyme is associated with hyperinsulinism-hyperammonemia syndrome, a genetic disorder characterized by excessive insulin secretion and elevated blood ammonia levels. Understanding the function and regulation of glutamate dehydrogenase is therefore critical for diagnosing and treating related metabolic disorders.

See Also

• Amino acid metabolism
• Citric acid cycle
• Urea cycle
• Enzyme regulation

‎

---

Translate: - East Asian 中文, 日本, 한국어, South Asian हिन्दी, தமிழ், తెలుగు, Urdu, ಕನ್ನಡ, Southeast Asian Indonesian, Vietnamese, Thai, မြန်မာဘာသာ, বাংলা
European español, Deutsch, français, Greek, português do Brasil, polski, română, русский, Nederlands, norsk, svenska, suomi, Italian
Middle Eastern & African عربى, Turkish, Persian, Hebrew, Afrikaans, isiZulu, Kiswahili,
Other Bulgarian, Hungarian, Czech, Swedish, മലയാളം, मराठी, ਪੰਜਾਬੀ, ગુજરાતી, Portuguese, Ukrainian