Nicotinamide function

Although nicotinic acid and nicotinamide function identically as vitamins, their pharmacologic effects differ. In large doses (up to 6 g/day), nicotinic acid is effective in reducing serum lipids (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides, and lipoprotein A. Nicotinic acid produces vasodilation and increased blood flow due to histamine release. Nicotinamide does not affect blood lipid levels or the cardiovascular system. 

GVGVP GFGVP GVGVP GVGK[NMeN]P) D-K/IF of Table 5.5, where n is for the aspartic acid residue with the side chain, -CH2-COOH, that accompanies the N-methyl nicotinamide functional group attached to a lysine side chain. Reduction of NMeN to form NMeN shifts the transition zone for protonation of the carboxyl function by 2.5 pH units. This shows electrochemical transduction, the conversion of electrical energy into chemical energy. In particular, the reduction reaction is carried out near pH 9, where the reduced NMeN is most stable. 

In an exactly analogous manner, equivalent behavior is seen with the series of Model Proteins il, in, and iv of Table 5.5 containing the nicotinamide functional group attached to a lysine (Lys, K) residue by an amide linkage (See Figure 5.20C).The systematic replacement of V by F shifts the reduction potential of the nicotinamide, that is, shifts the transition zone to lower electron concentrations, and results in a narrower transition zone. Figure 5.20C represents an explicit experimental example of the schematic representation in Figure 5.19C. 

Nicotinamide functions in the animal body as the active group of two important coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).These coenzymes are involved in the mechanism of hydrogen transfer in living cells (see Chapter 9) NAD is involved in the oxidative phosphorylation system, the tricyclic acid (TCA) cycle and the metabolism of many molecules, including pyruvate, acetate, (3-hydroxy-butyrate, glycerol, fatty acids and glutamate NADPH is the hydrogen acceptor in the pentose phosphate pathway. 

Biochemical role. Nicotinamide functions as a constituent of the pyridine nudeo-tides, which occupy a central role as hydrogen-transferrii coenzymes (transport metabolites for hydrogen). 

Niacin in the form of nicotinamide functions as an essential component of the enzyme co-factors NAD(H) and NADP(H) which are involved in approximately 200 enzyme reactions. NADH is involved extensively in energy metabolism where glucose in metabolised to produce ATP, the main energy storage molecule in the body. 

FIGURE 15 5 Structure of NAD the oxidized form of the coenzyme nicotinamide adenine dinucleotide The functional part of the coen zyme is framed in red... 

Ammonia reacts with the ketone carbonyl group to give an mine (C=NH) which is then reduced to the amine function of the a ammo acid Both mine formation and reduc tion are enzyme catalyzed The reduced form of nicotinamide adenine diphosphonu cleotide (NADPH) is a coenzyme and acts as a reducing agent The step m which the mine is reduced is the one m which the chirality center is introduced and gives only L glutamic acid... 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

NAD+ possesses some non-redox functions as well. The glycosidic linkage between nicotinamide and ribose is a high-energy bond. The energy provided by... 

Niacin Nicotinic acid, nicotinamide Coenzyme in oxidation and reduction reactions, functional part of NAD and NADP Pellagra—photosensitive dermatitis, depressive psychosis... 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

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. 

Human CYPs are multicomponent enzyme systems, requiring at a minimum the CYP enzyme component and a reductase component to be functional. The reductase requires a reduced nicotinamide cofactor, typically NADPH, and this cofactor must be regenerated to provide a steady supply of reducing equivalents for the reductase. Regeneration is accomplished with a separate substrate and enzyme. Glucose-6-phosphate and glucose-6-phosphate dehydrogenase have been widely used for this purpose. The overall complexity of the reaction mixtures and their cost have been barriers to the widespread use of recombinant human CYPs for metabolite synthesis in the past. 

In the Kohn-Sham Hamiltonian, the SVWN exchange-correlation functional was used. Equation 4.12 was applied to calculate the electron density of folate, dihydrofolate, and NADPH (reduced nicotinamide adenine dinucleotide phosphate) bound to the enzyme— dihydrofolate reductase. For each investigated molecule, the electron density was compared with that of the isolated molecule (i.e., with VcKt = 0). A very strong polarizing effect of the enzyme electric field was seen. The largest deformations of the bound molecule s electron density were localized. The calculations for folate and dihydrofolate helped to rationalize the role of some ionizable groups in the catalytic activity of this enzyme. The results are,... 

Dehydrogenases, which represent a majority of redox enzymes, are mostly NAD (Nicotinamide Adenine Dinucleotide, see Fig. 12.9) dependent. This cofactor is not directly bound to the enzyme but its presence in the medium is necessary because it acts as a carrier of two electrons and one proton, and it activates the biocatalytic function of the enzyme. 

The answers are 34-g, 35-a, 36-d. (Katzung, pp 53—56J There are four major components to the mixed-function oxidase system (1) cytochrome P450, (2) NAD PH, or reduced nicotinamide adenine dinucleotide phosphate, (3) NAD PH—cytochrome P450 reductase, and (4) molecular oxygen. The figure that follows shows the catalytic cycle for the reactions dependent upon cytochrome P450. 

The asymmetric reduction of prochiral functional groups is an extremely useful transformation in organic synthesis. There is an important difference between isolated enzyme-catalyzed reduction reactions and whole cell-catalyzed transformations in terms of the recycling of the essential nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] cofactor. For isolated enzyme-catalyzed reductions, a cofactor recycling system must be introduced to allow the addition of only a catalytic amount (5% mol) of NAD(P)H. For whole cell-catalyzed reductions, cofactor recycling is automatically achieved by the cell, and the addition of a cofactor to the reaction system is normally not required. 

Hexachloroethane is metabolized by the mixed function oxidase system by way of a two-step reduction reaction involving cytochrome P-450 and either reduced nicotinamide adenine dinucleotide phosphate (NADPH) or cytochrome b5 as an electron donor. The first step of the reduction reaction results in the formation of the pentachloroethyl free radical. In the second step, tetrachloroethene is formed as the primary metabolite. Two chloride ions are released. Pentachloroethane is a minor metabolic product that is generated from the pentachloroethyl free radical. 

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