Dietary nucleotides

Hawkes, J. S., Gibson, R. A., Roberton, D., and Makrides, M. (2006). Effect of dietary nucleotide supplementation on growth and immune function in term infants A randomized controlled trial. Eur.. Clin. Nutr. 60, 254-264. 

Carver JD, Pimentel B, Cox WI, Harness LA. 1991. Dietary nucleotide effects upon immune function in infants. Pediatrics 88 359-363. 

Delion S, Chalon S, Herault J, Guilloteau D, Besnard JC, Durand G. 1994. Chronic dietary alpha-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. J Nutr 124 2466-2476. DeLucchi C, Pita ML, Faus MJ, Molina JA, Uauy R, Gil A. 1987. Effects of dietary nucleotides on the fatty acid composition of erythrocyte membrane lipids in term infants. J Pediatr Gastroenterol Nutr 6 568-574. DeRisi JL, Iyer VR. 1999. Genomics and array technology. Curr Opin Oncol 11 76-79. 

Inosine monophosphate and GMP are synthesized in the human body and play diverse roles in cellular metabolism [3]. Dietary nucleotides are energetically useful to fulfill the liver s need for nucleotides [4], although people with high levels of uric acid (UA) in their blood and urine must avoid foods with these compounds, because degradation of purine nucleotides leads to the formation of UA [3]. In addition, these flavor enhancers are added by food manufacturers to improve the taste of food. Therefore, monitoring these compounds in foods or food seasonings is very important in food-quality or foodprocessing control. 

Lopez Navarro, A. T, J. D. Bueno, A. Gil, and A. Sanchez Pozo. 1996. Morphological changes in hepatocytes of rats deprived of dietary nucleotides. Brit. J. Nutr. 76 579-589. 

Dietary nucleotides in broilers Effects on productive performances and intestinal morphometry... 

Tabk 1. Effects of dietary nucleotides on technical performance of broilers. 

Van Buren, C.T. and F. Rudolph. 1997. Dietary nucleotides a conditional requirement. Nutrition. 13, 470-472. Zhang, G.Q., Q.G. Ma and C. Ji. 2008. Effects of dietary Inosinic Acid on carcass characteristics, meat quality, and deposition of Inosinic Acid in broilers. Poultry Sci. 87, 1364-1369. 

Hopes for the control of sea lice using immunostimulants have not yet been fully realised. Burrells et al. (2001) supplemented Atlantic salmon diet with dietary nucleotides for three weeks and achieved a 37% reduction in the mean number of attached lice per fish following an experimental... 

BURRELLS c, WILLIAMS p D and FORNO p F (2001), Dietary nucleotides a novel supplement in fish feeds 1. Effects on resistance to disease in satmonids, Aquaculture, 199,159-169. 

The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not generate ATP but has two major functions (1) The formation of NADPH for synthesis of fatty acids and steroids and (2) the synthesis of ribose for nucleotide and nucleic acid formation. Glucose, fructose, and galactose are the main hexoses absorbed from the gastrointestinal tract, derived principally from dietary starch, sucrose, and lactose, respectively. Fructose and galactose are converted to glucose, mainly in the liver. 

Human tissues can synthesize purines and pyrimidines from amphibolic intermediates. Ingested nucleic acids and nucleotides, which therefore are dietarily nonessential, are degraded in the intestinal tract to mononucleotides, which may be absorbed or converted to purine and pyrimidine bases. The purine bases are then oxidized to uric acid, which may be absorbed and excreted in the urine. While little or no dietary purine or pyrimidine is incorporated into tissue nucleic acids, injected compounds are incorporated. The incorporation of injected [ H] thymidine into newly synthesized DNA thus is used to measure the rate of DNA synthesis. 

The purines from which uric acid is produced originate from three sources dietary purine, conversion of tissue nucleic acid to purine nucleotides, and de novo synthesis of purine bases. 

A. Salvage pathways allow synthesis of nucleotides from free purines or pyrimidines that arise from nucleic acid degradation or dietary sources, which is more economical for the cell than de novo synthesis. 

Vitamin B12 consists of a porphyrin-like ring with a central cobalt atom attached to a nucleotide. Various organic groups may be covalently bound to the cobalt atom, forming different cobalamins. Deoxyadenosylcobalamin and methylcobalamin are the active forms of the vitamin in humans. Cyanocobalamin and hydroxocobalamin (both available for therapeutic use) and other cobalamins found in food sources are converted to the active forms. The ultimate source of vitamin Bi2 is from microbial synthesis the vitamin is not synthesized by animals or plants. The chief dietary source of vitamin Bi2 is microbially derived vitamin B12 in meat (especially liver), eggs, and dairy products. Vitamin Bi2 is sometimes called extrinsic factor to differentiate it from intrinsic factor, a protein normally secreted by the stomach that is required for gastrointestinal uptake of dietary vitamin B12. 

Vitamin B12 consists of a porphyrin-like ring structure, with an atom of Co chelated at its centre, linked to a nucleotide base, ribose and phosphoric acid (6.34). A number of different groups can be attached to the free ligand site on the cobalt. Cyanocobalamin has -CN at this position and is the commercial and therapeutic form of the vitamin, although the principal dietary forms of B12 are 5 -deoxyadenosylcobalamin (with 5 -deoxyadeno-sine at the R position), methylcobalamin (-CH3) and hydroxocobalamin (-OH). Vitamin B12 acts as a co-factor for methionine synthetase and methylmalonyl CoA mutase. The former enzyme catalyses the transfer of the methyl group of 5-methyl-H4 folate to cobalamin and thence to homocysteine, forming methionine. Methylmalonyl CoA mutase catalyses the conversion of methylmalonyl CoA to succinyl CoA in the mitochondrion. 

Degradation of dietary nucleic acids occurs in the small intestine, where a family of pancreatic enzymes hydrolyzes the nucleotides to nucleosides and free bases. Inside cells, purine nucleotides are sequentially degraded by specific enzymes, with uric acid as the end product of this pathway. [Note Mammals other than primates oxidize uric acid further to allantoin, which, in some animals other than mammals, may be further degraded to urea or ammonia.]... 

The so-called salvage pathways are available in many cells to scavenge free purine and pyrimidine bases, nucleosides, and mononucleotides and to convert these to metabolically useful di- and trinucleotides. The function of these pathways is to avoid the costly (energy) and lengthy de novo purine and pyrimidine biosynthetic processes. In some cells, in fact, the salvage pathways yield a greater quantity of nucleotides than the de novo pathways. The substrates for salvage reactions may come from dietary sources or from normal nucleic acid turnover processes. 

NAD A Coenzyme Nicotinamide adenine dinucleotide (NAD) is one of the principal oxidation-reduction reagents in biological systems. This nucleotide has the structure of two D-ribose rings (a dmucleotide) linked by their 5 phosphates. The aglycone of one ribose is nicotinamide, and the aglycone of the other is adenine. A dietary deficiency of nicotinic acid (niacin) leads to the disease called pellagra, caused by the inability to synthesize enough nicotinamide adenine dinucleotide. 

The general scheme for the degradation of nucleic acids has much in common with that of proteins. Nucleotides are produced by hydrolysis of both dietary and endogenous nucleic acids. The endogenous (cellular) polynucleotides are broken down in lysosomes. DNA is not normally turned over rapidly, except after cell death and during DNA repair. RNA is turned over in much the same way as protein. The enzymes involved are the nucleases deoxyribonucleases and ribonucleases hydrolyze DNA and RNA, respectively, to oligonucleotides which can be further hydrolyzed (Fig. 15-18), so eventually purines and pyrimidines are formed. 

It is not strictly correct to regard niacin as a vitamin. Its metabolic role is as the precursor of the nicotinamide moiety of the nicotinamide nucleotide coenzymes, nicotinamide adenine dinucleotide (NAD) and NADP, and this can also be synthesized in vivo from the essential amino acid tryptophan. At least in developed countries, average intakes of protein provide more than enough tryptophan to meet requirements for NAD synthesis without any need for preformed niacin. It is only when tryptophan metabolism is disturbed, or intake of the amino acid is inadequate, that niacin becomes a dietary essential. 

Niacin is present in tissues, and therefore in foods, iargeiy as the nicotinamide nucleotides. The postmortem hydrolysis of NAD(P) is extremely rapid in animal tissues, and it is likely that much of the niacin of meat (a major dietary source of the vitamin) is free nicotinamide. 

Nicotinamide nucleotides present in the intestinal lumen are hydrolyzed to nicotinamide. A number of intestinal bacteria have high nicotinamide deami-dase activity, and a significant proportion of dietary nicotinamide may be deamidated in the intestinal lumen. Both nicotinic acid and nicotinamide are absorbed from the small intestine by a sodium-dependent saturable process. 

A number of studies have investigated the equivalence of dietary tryptophan and preformed niacin as precursors of the nicotinamide nucleotides, generally by determining the excretion of -methyl nicotinamide and methyl pyridone carboxamide in response to test doses of the precursors, in subjects maintained on deficient diets. 

Apart from the relatively small amounts that are required for synthesis of the neurotransmitter serotonin (5-hydroxytryptamine), and for net new protein synthesis, essentially the whole of the dietary intake of tryptophan is metabolized by way of the oxidative pathway shown in Figures 8.4 and 9.4, which provides both a mechanism for total catabolism by way of acetyl coenzyme A and a pathway for synthesis of the nicotinamide nucleotide coenzymes (Section 8.3). 

Bender DA, Magboul Bl, and Wynick D (1982) Probable mechanisms of regulation of the utilization of dietary tryptophan, nicotinamide and nicotinic acid as precursors of nicotinamide nucleotides in the rat. British Journal of Nutrition 48, 119-27. 

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