NAD

Overview

Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is involved in redox reactions, carrying electrons from one reaction to another. This molecule exists in two forms: an oxidized form (NAD⁺) and a reduced form (NADH). NAD is essential for the function of several enzymes, including those involved in glycolysis, the citric acid cycle, and the electron transport chain.

Structure and Function

NAD consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base, and the other contains nicotinamide. The nicotinamide ring is the site of reversible reduction and oxidation, which is central to NAD's role in metabolism.

Redox Reactions

In redox reactions, NAD⁺ accepts electrons from other molecules, becoming reduced to NADH. This process is crucial in cellular respiration, where NADH carries electrons to the electron transport chain, ultimately producing ATP. NADH is oxidized back to NAD⁺, allowing the cycle to continue.

Enzymatic Roles

NAD acts as a coenzyme for various dehydrogenases, which are enzymes that catalyze the removal of hydrogen atoms from substrates. For example, in glycolysis, glyceraldehyde 3-phosphate dehydrogenase uses NAD⁺ to oxidize glyceraldehyde 3-phosphate, forming NADH.

Biosynthesis

NAD can be synthesized de novo from the amino acid tryptophan or from nicotinic acid (niacin). The salvage pathway, which recycles nicotinamide, is another significant route for NAD biosynthesis. Enzymes such as nicotinamide phosphoribosyltransferase (NAMPT) play a vital role in this pathway.

NAD in Cellular Processes

NAD is not only involved in redox reactions but also serves as a substrate for other important cellular processes. These include:

DNA Repair

NAD is a substrate for poly ADP-ribose polymerase (PARP) enzymes, which are involved in DNA repair. PARPs use NAD to add ADP-ribose units to proteins, a process known as ADP-ribosylation.

Sirtuins

NAD is also a substrate for sirtuins, a family of proteins that regulate cellular health and longevity. Sirtuins deacetylate proteins, influencing processes such as gene expression, apoptosis, and inflammation.

Clinical Significance

NAD levels decline with age, and this decline is associated with various age-related diseases. Research is ongoing to explore the potential of NAD-boosting therapies in treating conditions such as neurodegenerative diseases, cardiovascular diseases, and metabolic disorders.

NAD Precursors

Supplements such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are being studied for their ability to increase NAD levels. These precursors are thought to have potential therapeutic benefits in aging and age-related diseases.

NAD