Nicotinamide-adenine dinucleotide analogs

Nicotinamide adenine dinucleotide (NAD+ in its oxidized form) and its close analog nicotinamide adenine dinucleotide phosphate (NADP+) are composed of two nucleotides joined through their phosphate groups by a phosphoanhydride bond (Fig. 13-15a). Because the nicotinamide ring resembles pyridine, these compounds are sometimes called pyridine nucleotides. The vitamin niacin is the source of the nicotinamide moiety in nicotinamide nucleotides. 

FIGURE 13-15 NAD and NADR (a) Nicotinamide adenine dinucleotide, NAD +, and its phosphorylated analog NADP+ undergo reduction to NADH and NADPH, accepting a hydride ion (two electrons and one proton) from an oxidizable substrate. The hydride ion is added to either the front (the A side) or the back (the B side) of the planar nicotinamide ring (seeTable 13-8). (b)The UV absorption spec-... 

The niacin vitamers in foods include nicotinic acid and nicotinamide (Fig. 4), which occur in limited quantities in the free form, and their coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) (93,96). The nicotinic acid analog of NAD as well as nicotinamide and nicotinic acid mononucleotides also occur in nature. In addition, niacin occurs as nicotinyl esters bound to polysaccharides, peptides, and glycopep-tides, which are known as niacytin and niacynogens, respectively. In general, the niacin vitamers in cereal grains and other seeds are principally the nicotinic acid forms, whereas those in meat and fish are primarily the nicotinamide forms (94,95). 

A particular half-cell reaction, such as Equation 6.15, can accept or donate electrons. We quantitatively describe this by the redox potential for that reaction, as expressed by Equation 6.9 [Ej = E u — (RT/qF) In (reduced))/(oxidized))]. We will use (NADPH) to represent the activity of all of the various ionization states and complexed forms of the reduced nicotinamide adenine dinucleotide phosphate, and (NADP+) has an analogous meaning for the oxidized component of the NADP+-NADPH couple. For redox reactions of biological interest, the midpoint (standard) redox potential is usually determined at pH 7. By using Equation 6.9, in which the number q of electrons transferred per molecule reduced is 2, we can... 

Electrochemical oxidation of the reduced form (NADH) of nicotinamide adenine dinucleotide and its analogs has been investigated [262] best results are obtained using a carbon felt electrode. The results are consistent with an ECE mechanism yielding the pyridinium salt. Indirect oxidation of NADH (and reduction of NAD" ) is treated in Chapters 27 and 29. 

Fig. 1.5 Nicotinamide adenine dinucleotide (NAD+) and its phosphorylated analog (NADP+). The difference is indicated in purple. NAD+ and NADP+ undergo reduction to NADH and NADPH by accepting a hydride ion and two electrons and releasing a proton from an oxidized substrate. (Adapted from Fig. 14-13 in Berg JM, Tymoczko JL and Stryer L. Biochemistry, 5th Ed. 2002. W.H. Freeman Co., New York)...

The authors recognize that many biologically active purines are not reviewed herein, for example, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), as well as enzymatically modified analogs of ATP and GTP. These omissions are purposeful and have been instituted to limit the scope of the review. The reader is encouraged to peruse Chapter 4 within this volume for more examples. 

DHFR catalyzes the reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F) using nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor (Fig. 17.1). Specifically, the pro-R hydride of NADPH is transferred stereospecifi-cally to the C6 of the pterin nucleus with concurrent protonation at the N5 position [1]. Structural studies of DHFR bound with substrates or substrate analogs have revealed the location and orientation of H2F, NADPH and the mechanistically important side chains [2]. Proper alignment of H2F and NADPH is crucial in enhancing the rate of the chemical step (hydride transfer). Ab initio, mixed quantum mechanical/molecular mechanical (QM/MM), and molecular dynamics computational studies have modeled the hydride transfer process and have deduced optimal geometries for the reaction [3-6]. The optimal C-C distance between the C4 of NADPH and C6 of H2F was calculated to be 2.7A [5, 6], which is significantly smaller than the initial distance of 3.34 A inferred from X-ray crystallography [2]. One proposed chemical mechanism involves a keto-enol tautomerization (Fig. 

Double bonds conjugated with aldehydes or ketones can selectively be reduced with two different catalytic systems. Both systems use Hantzsch ester derivatives (HEH, 1) as hydride donor, analogous to nicotinamide adenine dinucleotide (NADH, 2), nature s reducing agent (Figure 32.1). These esters were first prepared by Hantzsch in 1882 from ethyl acetoacetate, formaldehyde, and ammonia. The... 

Tubereidin 6-amino-9-p-D-ribofuranosyl-7-deaza-purine, M, 266.25, m.p. 247-248 °C (d.), [a] j -67° (c = 1, 50% acetic acid), a purine antibiotic (see Nucleoside antibiotics) from Streptomyces tubercidicus, and one of the group of 7-deaza-adenine-nucleoside analogs. The N7 of adenine is replaced by a methylene group. T. is biosynthesized from adenosine (Fig.) the C-atoms of the pyrrole ring are derived from a ribose moiety, which is introduced from 5-phosphoribosyl 1-pyrophosphate. As an antimetabolite of adenosine, T. interferes with purine metabolism. T. can also be eonverted into nicotinamide-dea-za-adenine dinucleotide, which inhibits glycolysis. T. is particularly active against Mycobacterium tuberculosis and Candida albicans. 

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