Nucleotide Coenzyme Synthesis

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12.9— Nucleotide Coenzyme Synthesis
Nicotinamide adenine dinucleotide (NAD+), flavin adenine nucleotide (FAD), and coenzyme A (CoA) serve as important coenzymes in intermediary metabolism. These coenzymes are synthesized by a variety of mammalian cell types. Figures 12.32 (p. 513), 12.33, and 12.34 present the biosynthetic pathways for each. NAD+ synthesis requires niacin, FAD synthesis requires riboflavin, and CoA requires pantothenic acid. NAD can be synthesized by three different pathways starting from tryptophan (see p. 475), nicotinate, or nicotinamide. When tryptophan is in excess of the amount needed for protein synthesis and serotonin synthesis, it is used for NAD+ synthesis. This situation is not likely in most normal diets and, consequently, niacin is required in the diet.
Each of these coenzymes has an AMP moiety as part of the molecule.
Figure 12.33 Synthesis of FAD.
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Figure 12.34 Synthesis of CoA.
However, the AMP is not directly involved in the functional part of the molecule since electron transfer in NAD+ or FAD occurs via the niacin or riboflavin rings, respectively, and activation of acyl groups occurs through the –SH group of CoA. Synthesis of NAD+ by any of the three pathways requires utilization of PRPP as the ribose 5­phosphate donor. Nicotinamide adenine dinucleotide phosphate (NADP+) is synthesized from NAD+. NAD+ is used not only as a cofactor in oxidation–
reduction reactions but also as a substrate in ADP­ribosylation reactions (e.g., DNA repair and pertussis toxin poisoning). These reactions lead to the turnover of NAD+. The end product of NAD+ degradation is 2­pyridone­5­carboxamide, which is excreted in urine. Synthesis of nucleotide coenzymes is regulated such that there are essentially "fixed" concentrations of these coenzymes in the cell. When the statement is made that a certain