Official Full Name
NAD Synthetase
Background
In enzymology, a NAD+ synthase (EC 6.3.1.5) is an enzyme that catalyzes the chemical reaction:ATP + deamido-NAD+ + NH3↔ AMP + diphosphate + NAD+. The 3 substrates of this enzyme are ATP, deamido-NAD+, and NH3, whereas its 3 products are AMP, diphosphate, and NAD+. This enzyme belongs to the family of ligases, specifically those forming carbon-nitrogen bonds as acid-D-ammonia (or amine) ligases (amide synthases). This enzyme participates in nicotinate and nicotinamide metabolism and nitrogen metabolism.
Synonyms
EC 6.3.1.5; 9032-69-3; NAD+ synthetase; NAD+ synthase; nicotinamide adenine dinucleotide synthetase; diphosphopyridine nucleotide synthetase
NAD (nicotinamide adenine dinucleotide) is a coenzyme involved in a wide range of metabolic reactions in living organisms.The biosynthesis of NAD is highly regulated and tightly controlled, and NAD synthase plays a key role in its production.
Structure
NAD synthase is an enzyme that catalyzes the final step of NAD biosynthesis. It consists of a highly conserved catalytic structural domain responsible for the ATP-dependent condensation of nicotinamide mononucleotide (NMN) and adenosine triphosphate (ATP), resulting in the formation of NAD. Other structural motifs present in NAD synthetase confer substrate specificity, allosteric regulation, and interactions with cofactors or other proteins.
Functions
NAD synthetase plays a critical role in the synthesis of NAD. This form of coenzyme is essential for numerous cellular processes, serving as a cofactor for enzymes involved in redox reactions, energy metabolism, DNA repair, gene expression, and cellular signaling pathways. NAD synthesis ensures a sufficient pool of this coenzyme within the cell, ensuring its proper functioning.
NAD synthetase contributes to energy metabolism by enabling the conversion of nicotinamide to NMN, a key precursor in the NAD biosynthetic pathway. Through the production of NAD, the enzyme participates in glycolysis, the citric acid cycle, and oxidative phosphorylation, facilitating the transfer of electrons and the generation of ATP.
Applications
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Pharmaceutical and Biotechnology Research
Understanding the structure and function of NAD synthase paves the way for drug discovery and drug development. Targeting this enzyme offers potential therapeutic strategies for the treatment of various diseases such as cancer, neurodegenerative diseases and metabolic syndrome. Modulating NAD levels by regulating NAD synthase holds promise for manipulating cellular metabolism and enhancing cellular function.
NAD-dependent enzymes are widely used in industrial biocatalysis. The ability to produce NAD synthases in large quantities and engineer their activity has enabled the development of enzymatic reactions for the production of valuable chemicals, including pharmaceutical intermediates, specialty chemicals, and biofuels.
Clinical Significances:
NAD synthetase and the NAD-dependent enzymes it supports are implicated in age-related diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic dysfunctions. Altered NAD metabolism and decreased NAD levels contribute to cellular dysfunction and are considered potential therapeutic targets for interventions aimed at preventing or delaying the onset of age-related diseases.
NAD metabolism and NAD synthetase play crucial roles in cancer cell survival and proliferation. Manipulating NAD levels through targeting NAD synthetase can disrupt cancer cell metabolism and sensitize them to chemotherapy agents. Additionally, modulating NAD-dependent signaling pathways may offer novel therapeutic opportunities for targeted cancer treatments.
Conclusion
NAD synthase plays a crucial role in the biosynthesis of NAD, its structure and function open the door to the development of a variety of applications, including drug discovery, industrial biocatalysis, and therapeutic interventions for age-related diseases and cancer. Deepening our understanding of NAD synthase is critical to expanding our knowledge of NAD metabolism, cellular function, and potential therapeutic strategies. Continued research in this area is expected to reveal new insights into cellular metabolism and facilitate the development of innovative approaches to improve human health.
