Nicotinamide mononucleotide structure

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. ... 

Fig. 21. Stereogram ofthe nicotinamide binding site in the FNR(Y308->S)NADP complex. For clarity, only the isoalloxanzine and the ribityl portion of FAD and the nicotinamide mononucleotide portion of NADP are shown. Figure source Deng. Aliverti. Zanetti, Arakaki, Ottado, Orellano, Calcaterra, Ceccarelli, Carrillo and Karplus (1999) A productive NADP binding mode of ferredoxin-NADP reductase revealed by protein engineering and crystallographic studies. Nature Structural Biology 6 848...

Starting from the amino end of the polypeptide chain, the first structural element is which is the third strand from the left in Fig. 4b. Helices B and aC connect strands pA with /SB and /SB with /SC, respectively. These two helices are on the same side of the sheet. The sequence /SA, ffB, /SB, aC, and /SC is the AMP mononucleotide binding unit of these homologous enzymes. From /SC the chain passes back to the amino end of the sheet and into /8D which in the molecular structure is next to /SA. The sequence /SD, aE, /SE, alF, /SF forms the nicotinamide mononucleotide binding unit, with the helices E and alF on the opposite side of the sheet eompared to aB and aC. The number of residues from the beginning of /SA to the end of /SF are 144, 149, and 127 in LDH, GAPDH, and LADH, respectively. 

Nicotinamide (34) and structurally related 51 compounds were subjected to the halting activity bioassay to elucidate the structure-activity relationships [105]. The highest activity was recorded in thionicotinamide (35) followed by pyrazinamide (36) and nicotinamide (34). Nicotinamide adenine dinucleotide (NAD) (oxidized form), nicotinamide adenine dinucleotide phosphate (NADP) (oxidized form), (3-nicotinamide mononucleotide (oxidized form) showed halting activity at ca. 10"7 M... 

Figure 3.8. Structures of vitamins or vitamin-derived molecules that function in oxidation-reduction reactions. The oxidation of these redox groups in the inner mitochondricil membrane contributes to the electron transport chain that carries electrons from the oxidation of glucose to oxygen and in the process pumps protons from one side to the other of the inner mitochondrial membrane (see Chapter 8 for details). The proton gradient thus formed is used to phosphorylate ADP to form 32 of the 36 ATPs resulting from the oxidation of one glucose molecule to six CO2 and six H2O molecules. A Vitamin B3, also called niacin or nicotinic acid, becomes converted to the amide (nicotinamide) and dressed up with a ribose sugar. Then, in a manner like that of riboflavin in B becomes phosphorylated to form nicotinamide mononucleotide (NMN) or further reacted with the addition of adenosine monophosphate (AMP) to form nicotinamide adenine dinucleotide (NAD). B Vitamin B2, also known as riboflavin, is shown converted to the forms involved in redox reactions such as those of the electron transport chain. (From Biochemistry, Second Edition, D. Voet and J. Voet, Copyright 1995, John Wiley Sons, New York. Reprinted with permission of John Wiley Sons, Inc.)...

The coenzyme substrate, NAD+, is composed of two nucleotide moieties the nonfunctional adenosine monophosphate and the functional nicotinamide mononucleotide, which are connected by a pyrophosphate bridge. X-Ray structure analysis of the complex of enzyme and coenzyme have indicated that the interactions with the protein are hydrophobic ones for adenine, hydrophilic for the riboses of the two nucleotides, and ionic for the pyrophosphate group. In the neighborhood of the nicotina-... 

The second type of biological electron transfer involves a variety of small molecules, both organic and inorganic. Examples of these are (a) nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) as two electron carriers and (b) quinones and flavin mononucleotide (FMN), which may transfer one or two electrons. The structure of NAD and its reduced counterpart NADH are shown in Figure 1.12. 

Enzymatic cofactors, such as nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (EAD), flavin mononucleotide (EMN), and pyridoxal phosphate, are fluorescent and commonly found associated with various proteins where they are responsible for electron transport (see Fig. lb and Table 1). NADH and NADPH in the oxidized form are nonfluorescent, whereas conversely the flavins, FAD and EMN, are fluorescent only in the oxidized form. Both NADH and FAD fluorescence is quenched by the adenine found within their cofactor structures, whereas NADH-based cofactors generally remain fluorescent when interacting with protein structures. The fluorescence of these cofactors is often used to study the cofactors interaction with proteins as well as with related enzymatic kinetics (1, 9-12). However, their complex fluorescent characteristics have not led to widespread applications beyond their own intrinsic function. 

ACP = acyl carrier protein ACPA D = ACPA desat-urase AlkB = octane 1-monooxygenase AOX = alternative oxidase DMQ hydroxylase = 5-demethoxyquinone hydroxylase EXAFS = extended X-ray absorption fine structure spectroscopy FMN = flavin mononucleotide FprA = flavoprotein A (flavo-diiron enzyme homologue) Hr = hemerythrin MCD = magnetic circular dichroism MME hydroxylase = Mg-protophorphyrin IX monomethyl ester hydroxylase MMO = methane monooxygenase MMOH = hydroxylase component of MMO NADH = reduced nicotinamide adenine dinucleotide PAPs = purple acid phosphatases PCET = proton-coupled electron transfer, PTOX = plastid terminal oxidase R2 = ribonucleotide reductase R2 subunit Rbr = rubrerythrin RFQ = rapid freeze-quench RNR = ribonucleotide reductase ROO = rubredoxin oxygen oxidoreductase XylM = xylene monooxygenase. 

FIGURE 15.4 The structures of riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD). Even in organisms that rely on the nicotinamide coenzymes (NADH and NADPH) for many of their oxidation-reduction cycles, the flavin coenzymes fill essential roles. Flavins are stronger oxidizing agents than NAD and NADP. They can be reduced by both one-electron and two-electron pathways and can be reoxidized easily by molecular oxygen. Enzymes that use flavins to carry out their reactions—flavoenzymes—are involved in many kinds of oxidation-reduction reactions. 

FAD is similar in structure to DPN. It differs in that riboflavin replaces the nicotinamide riboside moiety. It is formed when red blood cells are incubated with riboflavin.A purified enzyme system from yeast catalyzes the synthesis of this coenzyme from ATP and flavin mononucleotide. ... 

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