Nicotinamide adenine dinucleotide phosphate, biological

The first step in the biological degradation of lysine is reductive animation with a-ketoglutarate to give saccharopine. Nicotinamide adenine dinucleotide phosphate (NADPH), a relative of NADH, is the reducing agent. Show the mechanism. 

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. 

Nicotinic acid derivatives occur in biologic materials as the free acid, as nicotinamide, and in two coenzymatic forms nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes act in series with flavoprotein enzymes and, like them, are hydrogen acceptors or, when reduced, donors. Several plants and bacteria use a metabolic pathway for the formation of nicotinic acid that is different from the tryptophan pathway used by animals and man (B39). 

Niacin is also known as vitamin PP or vitamin Bj. The term niacin describes two related compounds, nicotinic acid and nicotinamide (Figure 19.18), both with biological activity. Niacin is formed from the metabolism of tryptophan, and therefore it is not strictly a vitamin. It is a precursor of two cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for the functioning of a wide range of enzymes involved in redox reactions. 

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... 

NADP Nicotinamide adenine dinucleotide phosphate NADP and the related NAD (the reduced forms are NADPH2 and NADH2) are coenzymes that are involved in diverse oxidation-reduction reactions in biologic systems among the processes that require NADPH2 is the metabolism of many toxicants by microsomal enzymes in the mammalian liver. 

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... 

In biological systems, the most frequent mechanism of oxidation is the removal of hydrogen, and conversely, the addition of hydrogen is the common method of reduction. Nicotinamide-adenine dinucleotide (NAD) and nicotinamide-adenine dinucleotide phosphate (NADP) are two coenzymes that assist in oxidation and reduction. These cofactors can shuttle between biochemical reactions so that one drives another, or their oxidation can be coupled to the formation of ATP. However, stepwise release or consumption of energy requires driving forces and losses at each step such that overall efficiency suffers. 

The first step in XJVR-induced skin cancer is UVR-initiated DNA mutation, which causes the transformation of the normal cells to malignant cells. For UVR to initiate a biological reaction, it has to be absorbed by endogenous molecules (chromophores). UVB is absorbed directly by the DNA, and therefore can directly induce DNA mutation (224), in the form of thymine dimer formation (289). Some protein components may also ad as chromophores for UVB (224). UVA is absorbed by the reduced forms of the co-enzymes nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), tryptophan, riboflavin, and melanin (224,290). UVA-induced DNA damage is believed to be mediated by oxygen reactive species that are released after the absorption of UVA by those endogenous chromophores and results in photooxidation of selected bases... 

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. 

Involved in energy transfer in biochemical reactions. Uridine, cytidine, guanosine and thymine triphosphates are also common in biological systems. Nicotinamide adenine dinucleotide phosphate is also an important energy carrier. 

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