Niacin is a water-soluble vitamin. The RDA of niacin for the adult man is 19 mg. Niacin is converted in the body to the cofactor nicotinamide adenine dinucleotide (NAD). NAD also exists in a phosphorylated from, NADP. The phosphate group occurs on the 2-hydroxyl group of the AMP half of the coenzyme. NAD and NADP are used in the catalysis of oxidation and reduction reaction. These reaction are called redox reactions. NAD cycles between the oxidized form, NAD, and the reduced form, NADH + H+ . The coenzymes to accept and donate electrons. NADP behaves in a similar fashion. It occurs as NADP+. The utilization of NAD is illustrated in the section on glycosides, the malate-asparate shuttle, ketone body metabolism, and fatty acid oxidation. The utilization of NADP is illustrated in the sections concerning fatty acid synthesis and the pentose phosphate pathway.
The term niacin refer to both nicotinic acid and to nicotinamide. Niacin in foods occurs mainly in the cofactor form, NAD and NADP, and their reduced versions. NAD is hydrolyzed by enzymes of the gut mucosa to yield nicotinamide. Dietary NAD can also be hydrolyzed in the gut mucosa at the pyrophosphate bond to yield nicotinamide nucleotide. Nicotinamide and nucleotide are then broken down, possibly by enzymes in the gut and liver, to yield nicotinic acid. The conversion of nicotinic acid to NAD (nicotinamide adenine dinucleotide) is shown in Figure 9.62. The first step involves the transfer of a ribose phosphate groups from PRPP to nicotinic acid, forming nicotinic acid nucleotide. The second step involves the transfer of an ADP groups from ATP, forming nicotinic acid adenine dinucleotide. The final step is an amidation reaction. Here glutamine donates its adenine group to a carboxyl groups, forming NAD. The asterisk indicate the point of attachment of the phosphate groups of NADP.
Conversion of nicotinic acid to NAD is illustrated by the following experiment involving mice (Figure 9.63) the animals were injected with carbon-14-labeled nicotinic acid. The liver were removed at the indicated times -0.33, 1.0, 3.0, and 10 minutes-and used for analysis of the radiative metabolites. At 20 seconds, unchanged nicotinic acid (O) was the major metabolite. At 1 to 3 minutes, there was a temporary accumulation of nicotinic acid ribonucleotide
Biochemistry of NAD tends to be an electron acceptor in catabolic reactions involving the degradation of carbohydrates, fatty acids, ketone bodies, amino acids, and alcohol. NAD is used in energy-producing reactions. NADP, which is cytosolic, tends to be involved in biosynthetic reactions. Reduced NADP is generated by the pentose phosphate pathway (cytosolic) and used by cytosolic pathways, such as fatty acid biosynthesis and cholesterol synthesis, and by ribonucleotide reductase. The niacin coenzymes are used for two-electron transfer reactions. The oxidized from of NAD is NAD+. There is a positive charge on the cofactor because the aromic amino group is a quaternary amine. A quaternary amine participates in four covalent bonds. NAD-dependent reactions involve the transfer of two electrons and two protons. NAD accepts two of the electrons and one of the protons; the remaining proton remains in solution. Hence, the reduced from of NAD is not written as NADH2, but as NADH + H+ (Figure 9.64).
The niacin coenzymes might be compared with the riboflavin coenzymes. Niacin coenzymes are used by enzymes for the transfer of two electron at a time, where both electrons are transferred without the accumulation of a one-electron reduced intermediate. The riboflavin coenzymes, in accepting two electrons, can accept one electron at a time, with a detectable free radical intermediate. Another difference is that niacin coenzymes do not readily react with molecular oxygen, whereas riboflavin coenzymes can form covalent bond with oxygen. Hence, flavoenzymes are used for introducing oxygen, from O2 into various metabolites. Another difference is that the reducing power of NADH + H+ is greater than that of FADH2. Electrons from reduced NAD are often transferred to flavoproteins, resulting in a reduced flavoproteins; that is, the FAD cofactor is converted to FADH2. The reverse event, namely the reduction of NAD by FADH2 does not tend to occur. This point is illustrated by the fact that NADH + H+ can generate more ATPs in the respiratory chain than can FADH2. (Continue)
Source; Nutritional Biochemistry pages 593
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