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Regulating electron carrier molecules


The electron carrier molecule NAD+ is synthesized through two distinct pathways inside of the body. In the first pathway called the de novo pathway, NAD+ is synthesized from the amino acid tryptophan. In the second pathway, NAD+ is generated during the course of metabolism from the oxidation of NADH in the mitochondrial membrane.
In yeast experiments, deleting NPT1, which is a gene that encodes an enzyme in the de novo pathway, did not affect the levels of NAD+. Deleting QPT1, a gene that encodes the dehydrogenase enzyme that converts NADH to NAD+, on the other hand, significantly lowered the NAD+ levels. When doing a literature search to learn more about NAD+, the yeast researchers determined that, in healthy tissues, the ratio between free NAD+ and NADH (NAD+/NADH) molecules in the cytoplasm is approximately 1000. Interestingly, however, a different pair of electron carrier molecules, NADP+ and NADPH, which are similar in structure to NAD+ and NADH, are found in healthy tissues in a significantly lower ratio (NADP+/NADPH = 0.1). This study is described in Lin, S.-J. & Guarente, L. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr. Opin. Cell Biol. 15, 241–246 (2003).
Several diseases are associated with the NAD+:NADH ratio, which can regulate gene expression of several important genes. All of the following would be expected to alter the NAD+:NADH ratio EXCEPT:
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