Adenine metabolism

Aranda, A. Jimenez-Marti, E. Orozco, H. Matallana, E. del Olmo, M. Sulfur and Adenine Metabolisms Are Linked, and Both Modulate Sulfite Resistance in Wine Yeast. J. Agric. Food Chem. 2006, 54, 5839-5846. 

CS117 Fujimori, N. and H. Ashihara. CS128 Adenine metabolism and the synthesis of purine alkaloids in flowers of Camellia. Phytochemistry 1990 29(11) CS129... 

They may act as antagonists in the biosynthesis of purines, thymidine and amino acids. The fungicides may interfere with adenine metabolism at some site subsequent to its synthesis (Hollomon, 1979a). 

In vivo purine flow measured in L. donovani promastigotes confirms the active role of the adenine and guanine deaminases which lead to the production of hypoxanthine and xanthine, respectively (24). These two bases are metabolized to both adenine and guanine nucleotides. For this reason, although three different PRTases exist, the major route of adenine metabolism in promastigotes is through adenine deaminase to... 

Fig. 1 Metabolic pathways of purine metabolism showing the role of the salvage enzymes HGPRT and APRT and the alternative route of adenine metabolism when APRT is absent of inhibited. Adenine is not a product of purme nucleotide degradation in man but is produced as a by-product of the poly amine pathway.

Brown, D.R., Donavan, E.F., Tsang, R.C., Bobik, C.M., Chen, I.-W., and Johnson, J.R., 1978 Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands, J.Pediatr. 93 842 Kreuger, A., 1976 Adenine metabolism during and after exchange transfusions in newborn infants with CPD-Adenine blood. Transfusion 16 249... 

Table 1, Adenine metabolism in mammary gland explants of pregnant mice treated with various hormones...

The rate of adenine metabolism was enhanced, when insulin was used with prolactin or hydrocortisone, and it was highest when both of these hormones were added together (Table 2). 

Adenine metabol ism HypoxantKine metabolism Quanine metabol ism... 

The result of this biosynthesis is that the product is nicotinic acid mononucleotide rather than free nicotinic acid. Ingested nicotinic acid is converted to nicotinic acid mononucleotide which, in turn, is converted to nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide is then converted to nicotinamide adenine dinucleotide. If excess nicotinic acid is ingested, it is metabolized into a series of detoxification products (Fig. 4). Physiological metabohtes include /V-methylnicotinamide (19) and A/-methyl-6-pyridone-2-carboxamide (24) (1). 

Thus ATP is the effective controller of metabolism but because AMP + ADP + ATP is constant, it is really the ratio of adenine nucleotides which is important This ratio is termed die adenylate charge or energy charge and is expressed as ... 

Although the 3 - and 5 -polyphosphate derivatives mentioned above exhibit exquisite inhibitory potency these compounds are not cell permeable. To take advantage ofthepotency of such derivatives for studies with intact cells and tissues, there are two possibilities. One is chemically to protect the phosphate groups from exonucleotidases that also allows the compound to transit the membrane intact. The other is to provide a precursor molecule that is cell permeable and is then metabolized into an inhibitor by intracellular enzymes. The general term for such a compound is prodrug nucleotide precursors are also referred to as pronucleotides. Families of protected monophosphate derivatives were synthesized, based on (3-L- and 3-D-2, 5 -dd-3 -AMP, 3-L-2, 3 -dd-5 -AMP, and the acyclic 9-substituted adenines, PMEA and PMPA. Protective substituents were (i) -( -pivaloyl-2-thioethyl) ... 

NADP can be converted to nicotinic acid adenine dinucleotide phosphate (NAADP), which has distinct functions in the regulation of intracellular calcium stores. The studies of these new roles of NAD(P) in metabolism are in their early stages, but they might soon help to better understand and explain the symptoms of niacin deficiency ( pellagra) [1]. 

In both intermediate and maximum rates of respiration, control is distributed between several different steps, including the activity of the adenine nucleotide translocator (Groen et al., 1983). It is now recognized that the idea of a simple rate-limiting step for a metabolic pathway is simplistic and that control is shared by all steps although to different extents (Kacserand Bums, 1978 Fell, 1992). Each step in a pathway has a flux control coefficient (FCC) defined as ... 

Ethanol is oxidized by alcohol dehydrogenase (in the presence of nicotinamide adenine dinucleotide [NAD]) or the microsomal ethanol oxidizing system (MEOS) (in the presence of reduced nicotinamide adenine dinucleotide phosphate [NADPH]). Acetaldehyde, the first product in ethanol oxidation, is metabolized to acetic acid by aldehyde dehydrogenase in the presence of NAD. Acetic acid is broken down through the citric acid cycle to carbon dioxide (CO2) and water (H2O). Impairment of the metabolism of acetaldehyde to acetic acid is the major mechanism of action of disulfiram for the treatment of alcoholism. 

The samples of l,6-T2-DBpD and l,6-T2-2,3,7,8-Cl4-DBpD are useful in metabolism and mode of action studies. For example, when incubated with rabbit liver microsomes, l,6-T.>-DBpD is extensively metabolized to polar product(s) but only when these preparations are fortified with reduced nicotinamide-adenine dinucleotide phosphate. Under the same conditions l,6-T2-2,3,7,8-Cl4-DBpD is completely resistant to metabolic attack. In some types of studies, a higher specific activity possibly is desirable i.e., >1 Ci/mmole), and this can be achieved, with the methodology already developed, by using larger amounts of tritium gas or working on a larger synthetic scale so that it is not necessary to add unlabeled materials to assist in crystallization steps where a certain minimum amount of compound is necessary. 

Four of the B vitamins are essential in the citric acid cycle and therefore in energy-yielding metabolism (1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor in the a-ketoglutarate dehydrogenase complex and in succinate dehydrogenase (2) niacin, in the form of nicotinamide adenine dinucleotide (NAD),... 

Riboflavin fulfills its role in metabolism as the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) (Figure 45-10). FMN is formed by ATP-dependent phosphorylation of riboflavin, whereas FAD is synthesized by further reaction of FMN with ATP in which its AMP moiety is transferred to the... 

Sulphonamides are structural analogues of PABA. They competitively inhibit the incorporation of PABA into dihydropteroic acid and there is some evidence for their incorporation into false folate analogues which inhibit subsequent metabolism. The presence of excess PABA will reverse the inhibitory action of sulphonamides, as will thymine, adenine, guanine and methionine. However, these nutrients are not normally available at the site of infections for which the sulphonamides are used. 

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. 

Axcell BC, PJ Geary (1973) The metabolism of benzene by bacteria. Purification and some properties of the ezyme cw-l,2-dihydroxycyclohexa-3,5-diene (nicotinamide adenine dinucleotide) oxidoreductase (ciT-benzene glycol dehydrogenase). Biochem J 136 927-934. 

Xun L, ER Sandvik (2000) Characterization of 4-hydroxyphenylactate 3-hydroxylase (HpaB) of Escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase. Appl Environ Microbiol 66 481-486. Zaar A, J Gescher, W Eisenreich, A Bacher, G Fuchs (2004) New enzymes involved in aerobic benzoate metabolism m Azoarcus evansii. Mol Microbiol 54 223-238. 

Tirmenstein, M.A. and Nelson, S.D. (1990). Acetaminophen-induced oxidation of protein thiols contribution of impaired thiol metabolizing enzymes and the breakdown of adenine nucleotides. J. Biol. Chem. 2265, 3059-3065. 

Inflammatory cell phenomenon are also contributors to lipid peroxidation. Activated neutrophils may adhere to damaged endothelium and amplify traumatic, ischaemic or ischaemia-reperfiision injury. Many cyclooxygenase products of the metabolism of atachidonic acid modulate the inflammatory responses of cells. Macrophages, neutrophils and microglia are important sources of reactive oxygen at the injury site. When activated, they produce a respiratory burst that is traced to activated nicotinamide adenine dinucleotide (NADPH/NADH) oxidase. 

Acolbifene is also metabolized to a QM (Scheme 10.10)64 formed by oxidation at the C-17 methyl group. This QM is considerably more reactive compared to the tamoxifen quinone methide, which indicates that the acolbifene quinone methide is an electrophile of intermediate stability (Table 10.2). In addition, the acolbifene QM was determined to react with deoxynucleosides, with one of the major adducts resulting from reaction with the exocyclic amino group of adenine.64... 

Seasonal variations in the metabolic fate of adenine nucleotides prelabelled with [8—1-4C] adenine were examined in leaf disks prepared at 1-month intervals, over the course of 1 year, from the shoots of tea plants (Camellia sinensis L. cv. Yabukita) which were growing under natural field conditions by Fujimori et al.33 Incorporation of radioactivity into nucleic acids and catabolites of purine nucleotides was found throughout the experimental period, but incorporation into theobromine and caffeine was found only in the young leaves harvested from April to June. Methy-lation of xanthosine, 7-methylxanthine, and theobromine was catalyzed by gel-filtered leaf extracts from young shoots (April to June), but the reactions could not be detected in extracts from leaves in which no synthesis of caffeine was observed in vivo. By contrast, the activity of 5-phosphoribosyl-1-pyrophosphate synthetase was still found in leaves harvested in July and August. 

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