NAD+ synthase (glutamine-hydrolysing)

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NAD+ synthase (glutamine-hydrolysing) is an enzyme that plays a crucial role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for a wide range of metabolic processes and cellular functions. This enzyme catalyzes the final step in the NAD+ biosynthesis pathway, converting nicotinic acid adenine dinucleotide (NAAD) into NAD+ by hydrolyzing glutamine as an ammonia donor.

Function

NAD+ synthase (glutamine-hydrolysing) is involved in the NAD+ salvage pathway, which is critical for replenishing NAD+ levels within the cell. NAD+ is a key coenzyme that participates in oxidation-reduction reactions, serving as an electron carrier. It is vital for the production of ATP in the mitochondria, the regulation of gene expression, and the maintenance of DNA integrity and cell survival. The enzyme's activity ensures the continuous availability of NAD+, supporting the cell's metabolic demands and its ability to respond to stress and DNA damage.

Structure

The enzyme is composed of multiple domains, including a glutaminase domain that hydrolyzes glutamine to glutamate and ammonia, and a synthase domain that uses the ammonia to convert NAAD to NAD+. The structure of NAD+ synthase (glutamine-hydrolysing) is adapted to facilitate the efficient transfer of ammonia from the glutaminase active site to the synthase active site.

Mechanism

The catalytic mechanism of NAD+ synthase (glutamine-hydrolysing) involves two main steps. First, the enzyme binds glutamine and hydrolyzes it to produce glutamate and ammonia. Then, the ammonia is transferred internally to the synthase active site, where it reacts with NAAD to form NAD+. This process is tightly regulated to ensure that NAD+ production matches the cellular demand.

Clinical Significance

Alterations in NAD+ levels and NAD+ metabolism have been linked to various diseases and aging. As NAD+ plays a critical role in energy metabolism, DNA repair, and cell signaling, disruptions in its synthesis can contribute to the development of metabolic disorders, neurodegenerative diseases, and cancer. Therefore, understanding the function and regulation of NAD+ synthase (glutamine-hydrolysing) is important for developing therapeutic strategies aimed at modulating NAD+ levels in disease states.

See Also

• NAD+
• Metabolic pathway
• Coenzyme
• Biosynthesis