Nucleotide coenzymes functions

The nicotinamide nucleotide coenzymes function as electron carriers in a wide variety of redox reactions. In addition, NAD is the precursor of adenine dinucleotide phosphate (ADP)-ribose for ADP-ribosylation and poly(ADP-ribosylation) of proteins and cADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). They act as second messengers and stimulate increases in intracellular calcium concentrations. 

Although the nicotinamide nucleotide coenzymes function in a large number of oxidation and reduction reactions, thus carmot be exploited as a means of assessing the state of the body s niacin reserves, because the coenzymes are not firmly attached to their apoenzymes, as are coenzymes derived from thiamin (Section 6.5.3), riboflavin (Section 7.5.3), and vitamin Be (Section 9.5.3), but act as cosubstrates of the reactions, binding to and leaving the enzyme as... 

The pyridine nucleotides NAD and NADP always function in unbound form. The oxidized forms contain an aromatic nicotinamide ring in which the positive charge is delocalized. The right-hand example of the two resonance structures shown contains an electron-poor, positively charged C atom at the para position to nitrogen. If a hydride ion is added at this point (see above), the reduced forms NADH or NADPH arise. No radical intermediate steps occur. Because a proton is released at the same time, the reduced pyridine nucleotide coenzymes are correctly expressed as NAD(P)H+HT... 

The metabolic function of the flavin coenzymes is as electron carriers in a wide variety of oxidation and reduction reactions central to aU metabolic processes, including the mitochondrial electron transport chain. Unlike the nicotinamide nucleotide coenzymes (Section 8.4.1), which act as cosubstrates, leaving the catalytic site of the enzyme at the end of the reaction, the flavin coenzymes remain bound to the enzyme throughout the catalytic cycle. 

Figure 8.5. Redox function of the nicotinamide nucleotide coenzymes.

The sum reaction for the oxidative segment of the PPP is shown by reaction (1). Using insightful planning and remarkable chemistry, Warburg et al. (8) had also isolated and characterized (from 100 L of horse erythrocytes) the new pyridine nucleotide coenzyme NADP+ for the above reactions. He recognized and chemically established that the new coenzyme was functionally... 

An important aspect of the function of photosynthetic complexes is their asymmetric arrangement in respect to the membrane and to the external and internal phases of the cellular compartments. This arrangement allows the catalysis of vectorial electron transfer and the performance of electrical work by promoting charge separation across the membrane dielectric barrier. It allows also in some cases the net translocation of protons across the membrane. These two processes are at the basis of the mechanism of energy conservation in photosynthesis coupled to the formation of ATP, which is added, in oxygenic photosynthesis, to the conservation of redox energy in the form of reduced pyridine nucleotide coenzymes. 

The amino acids not only function as energy metabolites but also used as precursors of many physiologically important compounds such as heme, bioactive amines, small peptides, nucleotides and nucleotide coenzymes. In... 

In higher mammals, riboflavin is absorbed readily from the intestines and distributed to all tis.sues. It is the precursor in the biosynthesis of the cocnzyme.s flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The metabolic functions of this vitamin involve these Iwocoenzymes. which participate in numerous vital oxidation-reduction proces.ses. FMN (riboflavin 5 -phosphate) is produced from the vitamin and ATP by flavokinasc catalysis. This step con be inhibited by phcnothiazincs and the tricyclic antidepressants. FAD originates from an FMN and ATP reaction that involves reversible dinucicotide formation catalyzed by flavin nucleotide pyrophosphorylase. The.se coenzymes function in combination with several enzymes as coenzyme-en-zyme complexes, often characterized as, flavoproteins. 

The pentose phosphate pathway (PPP) is the major pathway for recycling nicotinamide adenine dinucleotide (NAD) to nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and for the production of ribose-5-phosphate that is needed for the synthesis of nucleotides. The function of the PPP depends on the synthesis of nicotinamide-adenine dinucleotide phosphate (NADP) and thiamin pyrophosphate, a coenzyme... 

Three families of coenzymes function primarily in amino acid and/or nucleotide metabolism. They include the following ... 

The aromatic hydroxylases or mixed-function oxidases are no exception to the above generalization. For maximum activity they require a transition metal ion and an electron donor such as one of the pyridine or flavin nucleotide coenzymes further, they probably utilize molecular oxygen as the source of the hydroxylic oxygen an example is the liver microsomal hydroxylating system (27). As yet there is no comprehensive explanation to cover the mode of action of these enzymes, for on the one hand there are the specific hydroxylases which catalyze such conversions as L-phenylalanine to L-tyrosine (26) or tryptophan to 5-hydroxytrypto-... 

More than 100 enzymes are Involved in the biosynthesis,modification,polymerisation, or degradation of nucleosides and nucleotides, many more act upon the polynucleotides, I A and RNA, or they require nucleotide coenzymes and nucleotides like ATP as cosubstrates or allosteric effectors. Besides their specific catalytic functions all these proteins should exhibit certain common modes of protein - nucleotide Interactions because the amino, Imlno, carbonyl, hydroxyl, and phosphate groups of nucleotides represent but a limited array of substituents capable to Interact with protein residues (Figure 1). There are, however, surprisingly few systematic studies on the structural origins of nucleotide specificity. 

In addition to the coenzyme function of retinal in vision another vitamin A derivative, retinoic acid, is an important hormone with effects on differentiation of cells and tissues. It acts to control transcription of the genetic messages in DNA by binding to specific protein receptors that in turn bind to specific nucleotide sequences of the DNA. The retinoid receptor proteins are a member of the steroid hormone receptor family. Also related to this family are receptors for hydroxylated derivatives of vitamin D. 

Transport of niacin between the liver and the intestine can occur in vivo, as indicated by radioactive probes in animals, and the liver appears to be a major site of conversion of niacin to its ultimate functional products the nicotinamide nucleotide coenzymes. Nicotinamide can pass readily between the cerebrospinal fluid and the plasma, thus ensuring a supply also to the brain and spinal cord. Liver contains greater niacin coenzyme concentrations than most other tissues, but all metabolically active tissues contain these essential... 

Coenzyme A is another adenine nucleotide derivative, with its primary functional group, a thiol, some distance away from the nucleotide end of the molecule. This thiol plays an important role in biochemistry via its ability to form thioesters with suitable acyl compounds (see Box 7.18). We have seen how thioesters are considerably more reactive than oxygen esters, with particular attention being paid to their improved ability to form enolate anions, coupled with thiolates being excellent leaving groups (see Box 10.8). 

The synthesis of purine nucleotides (1) starts from IMP. The base it contains, hypoxanthine, is converted in two steps each into adenine or guanine. The nucleoside monophosphates AMP and CMP that are formed are then phos-phorylated by nucleoside phosphate kinases to yield the diphosphates ADP and GDP, and these are finally phosphorylated into the triphosphates ATP and CTP. The nucleoside triphosphates serve as components for RNA, or function as coenzymes (see p. 106). Conversion of the ribonucleotides into deoxyribo-nucleotides occurs at the level of the diphosphates and is catalyzed by nucleoside diphosphate reductase (B). 

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