Nicotinamide-ribose-5 -phosphate

Specific nucleotide recognition in the ternary complex between the enzyme lactate dehydrogenase and the modified coenzyme NAD+-pyruvate (NAD = nicotinamide-adenine-dinucleotide). NAD+ consists of two nucleotides, adenosine-5 -phosphate and nicotinamide ribose-5 -phosphate, which are linked through a pyrophosphate bond. 

Bull seminal plasma also contains 5-nucleotidase activity. The enzyme has been purified from this source and found to split adenosine-5 -phosphate, uridine-5 -phosphate, cytidine-5 -phosphate, guanosine-5 -phosphate, and nicotinamide-ribose-5 -phosphate. Of several dozen other esters, only the desoxyribonucleotides have been found active as substrates. Snake venom contains a highly specific 5-nucleotidase which can be separated from phosphodiesterase by means of cellulose column chromatography. ... 

Acid hydrolysis of the coenzymes splits the glycosidic bond to the bases, as well as the pyrophosphate bridge. The products are thus nicotinamide, ribose-5-phosphate, and adenine. 

NMN is basically half of the NAD+ molecule nicotinamide ribose phosphate. NADP+ is NAD+ bearing a phosphate group at C3 of the ribose group attached to the adenine. The redox chemistry is the same in all three forms of the coenzymes. NAD+ is the form most frequently employed for biochemical oxidation reactions in catabohsm and NADP+ (in its reduced form NADPH) is the form usually employed for biochemical reduction reactions in anabohsm. NMN is employed infrequently. 

The presence of two coenzyme-binding sites is unexpected since they cannot be inferred solely from the crystal structure of CPR. Kinetic studies with wild t) e and W676H CPR at different concentrations of NADPH have, however, provided further support for the existence of two sites The rate of flavin reduction in the isolated FAD domain and CPR increases as NADPH is decreased from molar excess to stoichiometric concentrations. At stoichiometric concentration, the second noncatalytic site is predominantly vacant and the partial inhibition on the rate of flavin reduction from the catalytic site is therefore relieved (Figure 4.9). Occupation of the noncatalytic site occurs at NADPH concentrations in excess of the enzyme concentration, and impairs NADP" " release from the catalytic site. This in turn partially inhibits flavin reduction, the rate of which is gated by NADP release. Preincubation of the enzyme with a stoichiometric amount of adenosine 2, 5 -diphosphate does not lead to inhibition of the flavin reduction rate. We infer that the binding of adenosine 2, 5 -diphosphate prevents NADPH from binding to the noncatalytic site. This observation also suggests that it is the nicotinamide-ribose-phosphate portion of NADPH bound at the second site that hinders NADP" release from the catalytic site. Clearly, these new... 

The structure of this coenzyme is shown in Figure 2.2. It is made up of nicotinamide, ribose, phosphate and the nucleotide adenine. It exists in two forms, as shown. These differ in their oxidation state. NADP contains a pyridinium ring while NADPH contains a dihydropyridine. They can be interconverted by transfer of a hydride anion. The related coenzymes NAD and NADH are the same as NADP and NADPH except that they lack the phosphate ester at the 2 position (i.e. the... 

Lo HC, Leiva C, Buriez O, Kerr JB, Olmstead MM, Fish RH (2001) Bioorganometallic chemistry. 13. Regioselective reduction of NAD+ models, 1-benzylnicotinamide triflate and P-nicotinamide ribose-5 -methyl phosphate, with in situ generated [CpRh(Bpy)H]+ structure-activity relationships, kinetics, and mechanistic aspects in the formation of the 1,4-NADH derivatives. Inorg Chem 40 6705-6716... 

Both ribose phosphate and an AMP moiety must be added to nicotinamide in order to convert it to NAD-I-. The ribose phosphate is derived from PRPP when a phosphoribosyl transferase catalyzes the formation of nicotinamide ribonucleotide or nicotinamide mononucleotide. The final step utilizes ATP, which serves as an adenyl donor for the formation of the dinucleotide NAD-l-. 

Diphosphopyridine nucleotide, reduced form Adenine-D-ribose-phosphate-phosphate D-ribose-nicotinamide, reduced form Cozymase, reduced form... 

Figure A6.1 Structures of three of the vitamin-derived cofactors. NAD, like several other cofactors, has a handle consisting of adenine (blue) and ribose phosphate (black), but the actual chemistry of oxidation and reduction is done by the nicotinamide (red), which is derived from the vitamin nicotinic add or niacin. Note the positive charge on the ring nitrogen in the oxidised form, NAD+, which is shown here. Pyridoxal phosphate, derived from vitamin carries out its chemical contribution via the aldehyde group (mauve). Biotin likewise contributes its own characteristic chemistry, with the nitrogen atom, shown in blue, readily able to pick up CO2 as a carboxyl group.

It consists of the constituent mononucleotides, adenosine-5 -phosphate and nicotinamide mononucleotide, linked by a pyrophosphate bond. Splitting at the nicotinamide-ribose linkage yields nicotinamide and adenosine diphosphate ribose. This reaction is catalyzed by an enzyme from animal tissues and from Neurospora crassaJ The Neurospora enzyme appears in high concentration when the cells are grown on a zinc-deficient medium it has been purified from such material. The animal enzyme occurs in particles and has thus far not been solubilized. Both preparations are active with triphosphopyridine nucleotide (TPN), but reduced DPN is not split. 

In the rapid biosynthesis of DPN induced by the injection of nicotinamide, the increase in coenzyme is associated with a parallel rise of the liver acid-soluble adenine, nicotinamide, ribose, and phosphate 303). No changes in the concentrations of nucleic acids, or of 5 -adenylic acid, ADP, and ATP have been detected. These results show that formation of the newly synthesized pyridine coenz3rme does not occur at the expense of the... 

The most important product of the hexose monophosphate pathway is reduced nicotinamide-adenine dinucleotide phosphate (NADPH). Another important function of this pathway is to provide ribose for nucleic acid synthesis. In the red blood cell, NADPH is a major reducing agent and serves as a cofactor in the reduction of oxidized glutathione, thereby protecting the cell against oxidative attack. In the syndromes associated with dysfunction of the hexose monophosphate pathway and glutathione metabolism and synthesis, oxidative denaturation of hemoglobin is the major contributor to the hemolytic process. 

Nicotinamide adenine dinucleotide (NAD) Fructose 1,6-diphosphate Glucose-6-phosphate Isopentenyl pyrophosphate Ribose-6-phosphate-l-pyrophosphate... 

Two derivatives of nicotinamide (pyridine-3-carboxylic amide), one of the B2 vitamins, nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ), serve as redox coenzymes. Of the three heterocyclic ring systems found in these coenzymes, i.e. those of purine, ribose and pyridine, it is the pyridine portion that is reactive in redox reactions. Biologically, two oxidation states are important the oxidized form, NAD(P)+, and the 1,4-dihydro isomer of the two-electron reduced form, NAD(P)H (Scheme 1). Nicotinamide coenzymes interconvert between these two oxidation states in... 

One photoprocess reduces nicotinamide adenine dinucleotide phosphate (NADP ) to NADPH. These dinucleotides, shown below, differ from NAD and NADH (Section 15-6C) in having a phosphate group at C2 of one of the ribose units. The oxidized form, NADP , behaves like NAD and receives the equivalent of H e at C4 of the nicotinamide ring to form NADPH ... 

The two major products of the pathway are nicotinamide adenine dinucleotide (reduced form NADPH) and ribose 5-phosphate. Ribose 5-phosphate and its derivatives are components of important cellular molecules such as RNA, DNA, NAD+, flavine adenine dinucleotide (FAD), ATP and coenzyme A (CoA). NADPH is required for many biosynthetic pathways and particularly for synthesis of fatty acids and steroids. Hence the pathway is very active in tissues such as adipose tissue, mammary gland and the adrenal cortex. 

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