NAD Pathway

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms: an oxidized and reduced form abbreviated as NAD+ and NADH respectively.

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In metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The coenzyme is, therefore, found in two forms in cells: 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. These electron transfer reactions are the main function of NAD. However, it is also used in other cellular processes, most notably a substrate of enzymes that add or remove chemical groups from proteins, in posttranslational modifications. Because of the importance of these functions, the enzymes involved in NAD metabolism are targets for drug discovery.

In organisms, NAD can be synthesized from simple building-blocks (de novo) from the amino acids tryptophan or aspartic acid. In an alternative fashion, more complex components of the coenzymes are taken up from food as niacin. Similar compounds are released by reactions that break down the structure of NAD. These preformed components then pass through a salvage pathway that recycles them back into the active form. Some NAD is converted into nicotinamide adenine dinucleotide phosphate (NADP); the chemistry of this related coenzyme is similar to that of NAD, but it has different roles in metabolism.

Although NAD+ is written with a superscript plus sign because of the formal charge on a particular nitrogen atom, at physiological pH for the most part it is actually a singly charged anion (charge of minus 1), while NADH is a doubly charged anion.

 

NAD is a co-enzyme, signal molecule and neurotransmitter that is used by every cell in your body. Clincians having been using intravenous NAD to help individuals detoxify from chemical dependencies, aid in the reduction of the symptoms of most chronic conditions, and most recently has been used as a potential aging therapy.

Published in final edited form as:

Cell Metab. 2015 Jul 7; 22(1): 31–53.

Published online 2015 Jun 25. doi:  10.1016/j.cmet.2015.05.023

PMCID: PMC4487780

NIHMSID: NIHMS696097

NAD+ metabolism and the control of energy homeostasis – a balancing act between mitochondria and the nucleus

Carles Cantó,1,* Keir Menzies,2,* and Johan Auwerx2,#

Author information ► Copyright and License information ►

The publisher’s final edited version of this article is available at Cell Metab

See other articles in PMC that cite the published article.

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Abstract

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NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.

Keywords: NAD+ biosynthesis, NAD+ metabolism, NAD+ precursors, NAD+ therapeutics, energy signaling, mitochondrial function, Sirtuins, Poly(ADP-ribose) polymerases, Cyclic ADP-ribose synthases, Metabolic disease, Cancer, Neurodegenerative disease, Aging, Longevity

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INTRODUCTION

The importance of nicotinamide adenine dinucleotide (NAD+) metabolism became apparent subsenger of low NAD+)

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NAD+ has many important roles for health, including stimulating anti-aging activities of Sirtuins and the DNA damage repair enzymes.

High NAD+ is necessary for healthy metabolism and mitochondria. In addition, low NAD+ can contribute to fatigue and several diseases. Read this post to learn more about NAD+ and factors that increase or decrease it.

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