Niacin structure

Pellagra is a disease caused by a deficiency of niacm (C6FI5NO2) in the diet Niacin can be synthesized in the laboratory by the side chain oxidation of 3 methylpyndine with chromic acid or potassium permanganate Suggest a reasonable structure for niacin... 

Niacin is one of foe vitamin B vitamins (B3). Estimate foe approximate values of foe indicated bond angles. Its skeleton (not its Lewis structure) is given below. 

Niacin (Fig. 1) is a collective name for all vitamers having the biological activity associated with nicotinamide (= pyridine-3-carboxamide), including nicotinic acid (= pyridine-3-carboxylic acid) and a variety of pyridine nucleotide structures. 

Niacin. Figure 1 Structure of nicotinic acid and nicotinamide. 

Niacin. Figure 2 Structure of the coenzymes NAD+ (nicotinamide-adenine dinucleotid) and NADP+ (nicotinamide-adenine dinucleotid phosphate). 

Prior to the discovery of niacin receptors, medicinal chemistry efforts were mainly directed toward small heterocyclic carboxylic acids that are structurally similar to niacin. Systematic study of nitrogen-containing five- and six-membered heterocyclic carboxylic acids revealed that activity at GPR109A was significantly reduced for any of the variants of niacin shown in general structures (A and B) [45,46]. These heterocycles include pyrazole, isoxazole, thiazole, pyrazine, and pyrimidine. 

Niacin is a generic name for a small family of molecules having niacin biological activity. The most common structures that fall into this category are nicotinic acid and nicotinamide ... 

In contrast to most of the vitamins encountered so far, here we have simple structures. Humans are able to synthesize these molecules from the amino acid tryptophan but not in quantities adequate to meet physiological needs. Consequently, we need to find adequate amounts in our diet. The UL for niacin is 35 mg/day for adult men and women. 

Although the structures for molecules having niacin activity are simple, the forms in which they act in human biochemistry are not so simple. Nicotinic acid and nicotinamide are precursors for three complex coenzymes in multiple oxida-tion/reduction (redox) reactions nicotinamide mononucleotide, NMN nicotinamide adenine dinucleotide, NAD+ and nicotinamide adenine dinucleotide phosphate, NADP. I shall use NAD+ as representative of the class. NADH is the corresponding reduced form. ... 

As aromatic compounds have been exhausted as building blocks for life science products, A-heterocyclic structures prevail nowadays. They are found in many natural products, such as chlorophyll hemoglobin and the vitamins biotin (H), folic acid, niacin (PP), pyridoxine HCl (Be), riboflavine (B2), and thiamine (Bi). In life sciences 9 of the top 10 proprietary drugs and 5 of the top 10 agrochemicals contain A-heterocycIic moieties (see Tables 11.4 and 11.7). Even modern pigments, such as diphenylpyrazolopyrazoles, quinacri-dones, and engineering plastics, such as polybenzimidazoles, polyimides, and triazine resins, exhibit an A-heterocydic structure. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

FIGURE 13-17 Structures of niacin (nicotinic acid) and its derivative nicotinamide. The biosynthetic precursor of these compounds is tryptophan. In the laboratory, nicotinic acid was first produced by oxidation of the natural product nicotine—thus the name. Both nicotinic acid and nicotinamide cure pellagra, but nicotine (from cigarettes or elsewhere) has no curative activity. 

Niacin ia a nutritional term applied to both nicotinic acid and nicotinamide and to a mixture of the two. Their structures and those of their coenzymes are given in Table 6.1. Numerous redox reactions use NAD+ and NADP+ or NADH and NADPH. The latter are used largely in reactions designed to reductively synthesize various substances, mostly in the extramitochondrial areas of the cell. NAD+, on the other hand, is used largely in its oxidized form in catabolic redox reactions. The rat liver cytosol NADPH/NADP+ ratio is about 80, whereas its NADH/NAD+ ratio is only 8 x 10 4. Table 6.3 lists some biochemical reactions in which these cofactors participate. It shows that they are of crucial importance in the metabolism of carbohydrates, fats, and amino acids. 

NAD A Coenzyme Nicotinamide adenine dinucleotide (NAD) is one of the principal oxidation-reduction reagents in biological systems. This nucleotide has the structure of two D-ribose rings (a dmucleotide) linked by their 5 phosphates. The aglycone of one ribose is nicotinamide, and the aglycone of the other is adenine. A dietary deficiency of nicotinic acid (niacin) leads to the disease called pellagra, caused by the inability to synthesize enough nicotinamide adenine dinucleotide. 

Vitamins are chemicals that are necessary in trace amounts for normal body function. They are not produced in sufficient amounts by the body and must come from externa food sources. Their structures, like their diffuse locations in Biochemistryland, are generally diverse and unrelated, as shown in figures 9.1 and 9.2. Molecules that contain (or are) vitamins are indicated in green rectangles on the Biochem-isiryland map. There are actually many more loci on the map that contain vitamins, but which have not been included, to avoid cluttering the map. In particular, NADH (which contains niacin) has not been drawn in at many steps. 

Q-34 Describe briefly the structure of Niacin and its biochemical role. 

That nongrowing animals require niacin implies that it is lost from the body either as intact niacin or as a modified or breakdown product of the vitamin. An amount of niacin equivalent to nearly 90% of our daily intake is excreted in the forms of N-methyl-2-p)nidone-5urinary metabolites can be used to assess niacin status. Loss of the normal quantity in the urine each day indicates that the supply in the diet is adequate. In humans, the healthy adult excretes 4 to 6 mg of N-methyl-nicoti-namide per day. An abnormally low level indicates that the dietary intake is not adequate. Measurement of urinary niacin metabolites has proven useful in determining the amoimt of niacin available in a variety of foods. The body s ability to use niacin in different foods may vary even if the foods contain identical quantities of the vitamin. One contributing factor to the low availability of niacin is the occurrence of the vitamin in the "bound form," as mentioned earlier. Excretion of normal levels of pyridone, for example, depends not only on normal absorption of the vitamin from the diet, but also on its conversion to NAD or NADP, followed by catabolism to the metabolite. 

Nicotinic acid (niacin) was prepared first by oxidation of the alkaloid nicotine, but nut until 1913 was it isolated from yeast and recognized as an essential food factor (see tlu structures). In 1934-1935, nicotinamide was obtained from the hydrolysis of a coenzyme isolated from horse red blood cells. This coenzyme was later named coenzyme II and is now more commonly called nicolinainide adenine dinuclen-tide pho.iphate (NADP). 

A study of the formulas of coenzyme and prosthetic groups shows that many contain structures derived from the vitamins (see Chapter 30). Thus, the nicotinamide portion of NAD and NADP derives from the vitamin niacin, whereas the P-5 -P prosthetic group of the aminotransferases is a derivative of pyridoxine, vitamin Bg. Other derivatives of the B-group vitamins participate in enzymatic reactions. 

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