NAD+, friend to enzymes, friend to health

Nicotinamide adenine dinucleotide, or NAD, is a coenzyme, an enzyme that is a friend to other enzymes that enable all the chemical reactions that our cells and bodies need to work healthily, just as they should. It is also a substrate, a kind of workbench on which all of reactions can take place.

NAD does all this by taking a negatively charged electron from one enzyme, allowing it to become reactive. And then passing the spare electron on to another biochemical vital for human health. As it does this, it see-saws between its two main forms, positive NAD+ and negative NADH, as well as its cousins, including the phosphate family NADP and NADPH.

That enzymes and their associate biochemicals are reactive can be a good thing. It means that they can do things and react to the environment. However, if the balance isn’t right, they can actually cause damage. NAD+ is that good friend and coach that tells them when to make hay, or when to say nay.

What do these enzymes actually do?

There are a whole bunch of enzymes that lean on NAD+. At least 300, and counting, have so far been identified. There are organized into many different clubs. Certainly, the most famous are the sirtuins, PARPs, and NADases, which have different ways of acting, but often similar final goals.

Sirtuins, the seven Lord Sirs of enzymes

Humans have seven sirtuins that have been identified so far. Sirtuin 1 and 2 live in the cell nucleus, and hang out in the surrounding liquid, or cytoplasm. They deal with metabolism, that is, preparing fuel for the powerhouse of the cell, as well as inflammation and tumorigenesis, limiting the growth of cancerous cells. Sirtuin 3, 4 and 5 reside in the mitochondria, helping with burning the fuel for energy, as well as turning the insulin taps on to avoid diabetes, and removing the toxic by-product ammonia. The last two, 6 and 7, occupy, respectively, the nucleus and the nucleolus, or the nucleus of the nucleus. And these work on metabolism, DNA copying and repair, and producing the cancer killing factor TNF.

PARPs, the pen-pals

Poly ADP-ribose polymerases are nicknamed “the writers”, since this club of 17 spend their time transcribing, copying, recombining, and proofreading the fundamental instructions that tell every cell what to do and when, and how to defend themselves from attack.

NADases up our sleeves

NADases, or NAD⁺ glycohydrolases, are a lively club of multi-skilled enzymes that interact closely with NAD to perform a dizzying array of feats. An NADase is the kind of guy who gets everywhere and does everything, being able catalyze both the synthesis and hydrolysis of cyclic ADP-ribose, and break nucleotides into nucleosides and phosphate. While hanging around the corridors of power, or rather cell membranes - and those of nerve and immune cells in particular - they play a pivotal role in cell signaling, and, thus, reducing inflammation, fighting off disease, and killing off bad cells. Accordingly, they have been implicated in moderating ageing, rheumatoid arthritis, cancer, and neurodegenerative diseases.