Coenzyme as nucleotide

Typical biochemical hydrogenation (reduction) reactions are catalyzed by prosthetic enzymes with nicotinamide or flavin nucleotide as coenzyme. Model asymmetric hydrogenation of these types, however, await future stu s. 

From the livers of various animals has been isolated an enzyme named glucose dehydrogenase which, with di- or tri-phosphopyridine nucleotide as coenzyme, reversibly converts D-glucose to D-gluconolactone. It appears to be rather specific for fl-D-glucose, although /3-D-xylose can also be oxidized (at a lower rate). -... 

Several classes of vitamins are related to, or are precursors of, coenzymes that contain adenine nucleotides as part of their structure. These coenzymes include the flavin dinucleotides, the pyridine dinucleotides, and coenzyme A. The adenine nucleotide portion of these coenzymes does not participate actively in the reactions of these coenzymes rather, it enables the proper enzymes to recognize the coenzyme. Specifically, the adenine nucleotide greatly increases both the affinity and the speeifieity of the coenzyme for its site on the enzyme, owing to its numerous sites for hydrogen bonding, and also the hydrophobic and ionic bonding possibilities it brings to the coenzyme structure. 

Both the enzymes were prepared by a special technique from the insoluble portion of guinea pig liver mitochondria, and they are quite specific with respect to the requirement of pyridine nucleotide (H9, Hll). However, dehydrogenases catalyzing reaction (25) with NAD as coenzyme have been reported (Mil, S13, T3), thus confirming the importance of the source of the enzyme and the purification procedure employed. 

The pyridine nucleotides NAD"" and NADP" (1) are widely distributed as coenzymes of dehydrogenases. They transport hydride ions (2e and 1 see p. 32) and always act in soluble form. NAD" transfers reducing equivalents from catabolic pathways to the respiratory chain and thus contributes to energy... 

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). 

The mechanism of hepatotoxicity is therefore currently unclear. It has been suggested that lipid peroxidation is responsible rather than covalent binding to protein. Arylation of other low molecular weight nucleophiles such as coenzyme A and pyridine nucleotides also occurs and may be involved in the toxicity. Bromobenzene is known to cause the inhibition or inactivation of enzymes containing SH groups. It also causes increased breakdown of phospholipids and inhibits enzymes involved in phospholipid synthesis. Arylation of sites on... 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

In addition to their role in genetics, nucleotides play other important roles in biochemistry. Key enzymes and coenzymes such as nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD), and vitamin B12 also include nucleotides as part of their structures. Also, the major component of viruses is DNA. 

Nucleotides are stmctural units of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and cofactors such as coenzyme A (CoA), flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), with important roles in energy transfer, metabolism and intracellular signalling. 

Mitochondria contain ubiquinone (also known as coenzyme Q), which differs from plastoquinone A (Chapter 5, Section 5.5B) by two methoxy groups in place of the methyl groups on the ring, and 10 instead of 9 isoprene units in the side chain. A c-type cytochrome, referred to as Cyt Ci in animal mitochondria, intervenes just before Cyt c a h-type cytochrome occurring in plant mitochondria is involved with an electron transfer that bypasses cytochrome oxidase on the way to 02. The cytochrome oxidase complex contains two Cyt a plus two Cyt a3 molecules and copper on an equimolar basis with the hemes (see Fig. 5-16). Both the Fe of the heme of Cyt a3 and the Cu are involved with the reduction of O2 to H20. Cytochromes a, >, and c are in approximately equal amounts in mitochondria (the ratios vary somewhat with plant species) flavoproteins are about 4 times, ubiquinones 7 to 10 times, and pyridine nucleotides 10 to 30 times more abundant than are individual cytochromes. Likewise, in chloro-plasts the quinones and the pyridine nucleotides are much more abundant than are the cytochromes (see Table 5-3). 

The nicotinamide coenzymes are involved as proton and electron carriers in a wide variety of oxidation and reduction reactions. Before their chemical structures were known, NAD and NADP were known as coenzymes I and II. Later, when the chemical nature of the pyridine ring of nicotinamide was discovered, they were called diphosphopyridine nucleotide (DPN = NAD) and triphospho-pyridine nucleotide (TPN = NADP). The nicotinamide nucleotide coenzymes are sometimes referred to as the pyridine nucleotide coenzymes. 

Urease catalyzes the hydrolysis of urea to ammonia, while catalase is capable of rapidly decomposing II2O2 to H2O + 02. " In a number of cases, enzyme catalysis requires the participation of a smaller molecule usually referred to as a coenzyme. Many of the vitamins and simple nucleotides such as adenosine triphosphate (ATP) have been shown to act as coenzymes. 

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. 

Three classes of analogs have been studied a) analogs in which the 5,6-dimethylbenzimidazole moiety of the nucleotide has been replaced, b) analogs with modifications on the periphery of the corrin ring and c) analogs in which the S -deoxyadenosyl moiety has been altered or replaced. Coenzymes in which the 5,6-dimethylbenzimidazole moiety has been replaced by benzimidazole, 5-methoxybenzimidazole, adenine and 2-methyladenine have been tested with ribonucleotide reductase. Adenosylcobamides with benzimidazole and adenine function as coenzymes in the L. leichmannii system (52, 80), while those with 5-methoxybenzimidazole and 2-methyladenine are active with the R. meliloti reductase (82). In contrast adenosylcobinamide, which lacks the entire nucleotide moiety does probably not function as a coenzyme because it did not yield the rapidly appearing paramagnetic intermediate (77). 

The pentose-phosphate pathway, also known as the hexose monophosphate pathway, is a metabolic system with two important consequences. The first is production of NADPH for biosynthesis, and the second is production of ribose-5-phosphate for nucleotide and coenzyme biosynthesis (Fig. 12.5). 

Phosphoribosylpyrophosphate can be used in a number of reactions. It is important in the synthesis of purines, pyrimidine nucleotides, and coenzymes such as NAD+. Therefore, it would not be prudent for strict... 

In many of the examples cited of affinity labeling of enzymes by periodate-oxidized nucleotides, it has been assumed that the reaction involved formation of a Schiff base with an enzymic lysine, as in Fig. 3a,b. However, in very few papers has direct evidence been presented supporting the existence of a Schiff base intermediate. Lowe and Beechey (83), after examining in detail the structure of periodate-oxidized ATP, concluded that in aqueous solution there is little free aldehyde rather, the compound exists predominantly as an equilibrium mixture of three dialdehyde monohydrates (cyclic hemiacetals) and a dihydrate. The presence of cyclic hemiacetals may account for the ability of periodate-oxidized NADP and NADPH to function as coenzymes in several enzymic reactions (e.g., 78, 81). In many cases, the product of the covalent reaction of an enzyme and periodate-oxidized nucleotide may be a dihydroxymorpholino derivative (Fig. 3c), which is similar to the cyclic hemiacetals observed in aqueous solu-... 

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