beta-Diphosphopyridine nucleotide

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What is Beta-Nicotinamide Adenine Dinucleotide (NAD+)

NAD,Nicotinamide adenine dinucleotide is a indispensable cofactor involved in several redox reactions in all forms of cellular life.  It exists in two forms: an oxidized and reduced form abbreviated as NAD+ and NADH respectively.

NAD+ is an oxidizing agent - it accepts electrons from other molecules and becomes reduced.  This reaction forms NADH, which can then be used as a reducing agent to donate electrons. Both of these two stabilized form of NAD are marketed as a anti-age nutritional supplement, which is not under FDA regulation at the moment.

Beta-Nicotinamide Adenine Dinucleotide (NAD+) Benefits
NAD+/NADH plays a significant role in the reactions associated with glycolysis, oxidative phosphorylation, and fermentation.  Nicotinamide adenine dinucleotide(NAD) effects include the stimulation of dopamine, noradrenaline, and serotonin receptors, by which mechanism it is thought to increase mental alertness and clarity and improve concentration.

In the jet lag study, subjects who received NADH had significantly better cognitive performance and a trend toward reduced sleepiness on the first post-flight day than controls, and a smaller pilot study showed similar trends lasting through the second day.

In 2000, Guarente's lab reported that NAD fuels the activity of sirtuins, including SIRT1-the more NAD there is in cells, the more SIRT1 does beneficial things.  One of those things is to induce formation of new mitochondria.  NAD can also activate another sirtuin, SIRT3, which is thought to keep mitochondria (Mitochondria are our cells' energy dynamos.  Descended from bacteria that colonized other cells about 2 billion years, they get flaky as we age) running smoothly.

Beta-Nicotinamide Adenine Dinucleotide (NAD+) Mode of Action

Nicotinamide adenine dinucleotide has several essential roles in metabolism.  It acts as acoenzyme inredox reactions, as a donor of ADP-ribose moieties in ADP-ribosylation reactions, as a precursor of thesecond messenger molecule cyclic ADP-ribose, as well as acting as a substrate for bacterial DNA ligases and a group of enzymes called sirtuins that use NAD+ to remove acetyl groups from proteins.  In addition to these metabolic functions, NAD+ emerges as an adenine nucleotide that can be released from cells spontaneously and by regulated mechanisms, and can therefore have important extracellularroles.

The enzymes that make and use NAD+ and NADH are important in both pharmacology and the research into future treatments for disease.  Drug design and drug development exploits NAD+ in three ways: as a direct target of drugs, by designing enzyme inhibitors or activators based on its structure that change the activity of NAD-dependent enzymes, and by trying to inhibit NAD+biosynthesis.

The coenzyme NAD+ is not itself currently used as a treatment for any disease.  However, it is being studied for its potential use in the therapy of neurodegenerative diseases such asAlzheimer's andParkinson disease.  Evidence on the benefit of NAD+ in neurodegeneration is mixed;  some studies inmice have produced promising results whereas a placebo-controlled clinical trial in humans failed to show any effect.

NAD+ is also a direct target of the drug isoniazid, which is used in the treatment oftuberculosis, an infection caused by Mycobacterium tuberculosis.  Isoniazid is a prodrug and once it has entered the bacteria, it is activated by a peroxidase enzyme, which oxidizes the compound into a free radicalform.  This radical then reacts with NADH, to produce adducts that are very potent inhibitors of the enzymes enoyl-acyl carrier protein reductase, and dihydrofolate reductase.  In one experiment, mice given NAD for one week had improved nuclear-mitochrondrial communication.

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