Hi,

Living systems is a result of thousands of consecutive biological reactions, catalyzed by specific enzymes, in orchasetrated manners. NAD/NADH & NADP/NADPH are very important biological cofactors, participating mainly in numerous cellular oxidation/reduction reactions, as an electron acceptor(to be reduced) or donner(to be oxidized). There is another biological cofactor known as FAD(Flavine Adenine Dinucleotide) also participates in biological reactions. And the particular enzyme involved in each reaction, has strong choice (specificity) for its cofactor of either NAD or NADP or FAD, to catalyze the reaction optimally. This specific choice for cofactors of the catalyzing enzymes, makes other analogues unsuitable for biological reaction. The specificity depends on many factors as three dimensional conformity of the subustrates, enzymes, cocfactors and redox(reduction/oxidation) potential of the reaction & reactants etc.

Although there may be some artificial or synthetic analogues that may somehow support a biological reaction in lab conditions, the reation rate may not be optimum as in biological system. So, if cellular reactions do not run optimally, there must be some traffic congestion, thus making the whole system go-slow or idle (ageing?). All These make NAD/NADP so important. Good luck for you.

1- NAD is a dinucleotide consisting of two nucleotides; one adenine and the other nicotine linked together by their phosphate groups (phosphodiester bond).

2- Pyridine nucleotide analogs like NGD and MCT (molybdene cytosine dinucleotide)...etc. exist already.

Thanks for your answer Mohammad. I think you meant "nicotinamide" in your first answer. In any case, I see nicotinamide classified as a vitamin, not a nucleotide, or a vitamin can be a nucleotide too? sorry for my ignorance in biochemistry. Regarding your second answer, well, although NGD is chemically possible, it has no relevant role in cellular biology (as far as I know). So why NAD has that redox role almost exclusively?

Best regards.

sorry.. yes I mean nicotinamide.

when it is linked to ribose and phosphate it becomes a nicotinamide nucleotide (or mononucleotide), a well known anti-aging agent.

I agree with you. NAD+/NADH and NADP+/NADPH are well characterized and have effective role in redox homeostasis while analogs function does not make sense. I think that NAD is biosynthesized inside the cells while the others are chemically synthesized (in vitro).

Yes Mohammad, indeed only NAD (among all other analogues) is biosynthesized.. but that is a consequence of something special about it, which is exactly what I am trying to figure out. Best regards.

yes.. you should look out for genes involved in NAD/NADP biosynthesis.

thanks for your discussion and the publication you provided.

it is a very interesting question..

Best regards.

Hi,

The couple NAD/NADH2 is a redox respiratory substrate and the anaerobic redox substrate…

Hi,

Living systems is a result of thousands of consecutive biological reactions, catalyzed by specific enzymes, in orchasetrated manners. NAD/NADH & NADP/NADPH are very important biological cofactors, participating mainly in numerous cellular oxidation/reduction reactions, as an electron acceptor(to be reduced) or donner(to be oxidized). There is another biological cofactor known as FAD(Flavine Adenine Dinucleotide) also participates in biological reactions. And the particular enzyme involved in each reaction, has strong choice (specificity) for its cofactor of either NAD or NADP or FAD, to catalyze the reaction optimally. This specific choice for cofactors of the catalyzing enzymes, makes other analogues unsuitable for biological reaction. The specificity depends on many factors as three dimensional conformity of the subustrates, enzymes, cocfactors and redox(reduction/oxidation) potential of the reaction & reactants etc.

Although there may be some artificial or synthetic analogues that may somehow support a biological reaction in lab conditions, the reation rate may not be optimum as in biological system. So, if cellular reactions do not run optimally, there must be some traffic congestion, thus making the whole system go-slow or idle (ageing?). All These make NAD/NADP so important. Good luck for you.

Very Interesting, Kou. I always thought that the active transport was carried out using ATP to move protons through the membrane, now I learnt that NADH can also be used for that, which of course makes sense because NADH has its own protons for doing the same process. Now I wonder how exactly this works, I mean how the protons of NADH are separated because that is not something that occur spontaneously. Your article clearly demonstrate that that is what happens, but is it known exactly the molecular mechanism for this process?. For example, is the compound that is being transported the one that gets reduced by NADH?

Thanks for your time.

Thanks Tapan. Yes, there is also FAD (Flavin Adenine Dinucleotide), which further shows a natural tendency to almost exclusively use Adenine as part of the cofactors for these processess. My question still remains though, what makes Adenine (and not guanine, or other nucleotide) special for this?

Thanks Kou. I will read those documents now. Best regards.

Hi Ramirez,

In biological reactions, 3-dimensional spatial conformity (of participating enzymes, substrates and cofacotors) is very important to procced, just as in a [lock and key] relationship, and this is specificity. Moreover, the degree of affinity for each other also a deciding facotor. Good luck and thanks for you.

Dear Kou, thank you again for another interesting article. Did not know the importance of ingesting biotin and lipoic acid in adults. Looks like I will have to start consuming more: eggs, salmon, avocados (for biotin); and spinachs and broccoli (for lipoic acid). Regarding the article I cite above in the question, a natural food that contains a lot of Niacin (vit b3, precursor for NAD+) is japanese food called Edamame, made from immature soybeans. Unfortunately I have been unable to find these in my city. Best regards.