Nicotinamide adenine dinucleotide-dependent dehydrogenases (None)

Nicotinamide adenine dinucleotide (NAD)-dependent dehydrogenases are a large family of oxidoreductase enzymes that catalyze the transfer of electrons between substrates and the NAD+/NADH cofactor [1, 2]. These enzymes are essential for core metabolic processes, including glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway, thereby regulating cellular energy production and redox homeostasis [2, 4]. In oncology, specific dehydrogenases such as lactate dehydrogenase (LDH) and aldehyde dehydrogenase (ALDH) are often upregulated to support the metabolic reprogramming of cancer cells and provide resistance to oxidative stress [1, 3]. Additionally, these enzymes are critical for the survival of pathogens like Mycobacterium tuberculosis and Plasmodium falciparum, making them significant targets for antimicrobial and antiparasitic drug development [1, 2]. Drugs targeting this class, such as disulfiram and isoniazid, work by inhibiting enzyme activity to disrupt metabolic flux or cell wall synthesis [1, 3]. However, the high structural conservation of the NAD-binding Rossmann fold across many human enzymes presents a major challenge for achieving therapeutic selectivity and avoiding systemic toxicity [2].

Other names

NAD-dependent dehydrogenasesNADH-dependent dehydrogenasesNAD/NADH-dependent dehydrogenasesNAD-linked dehydrogenasesNAD-dependent oxidoreductases

Inhibition of enzymatic activity through competitive or non-competitive binding at the substrate or NAD+/NADH cofactor binding sites, leading to the disruption of essential metabolic pathways and cellular redox balance [1, 2].