Role of the liver in systemic pyridine nucleotide metabolism

Dietrich, L.S.; Martinez, L.; Franklin, Larissa

doi:10.1007/bf00606222

Cited by 4 publications

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“…The pathway involves nicotinate mononucleotide and nicotinate adenine dinucleotide as intermediates ( 1,2 ) . Animal tissue also contains enzyme (s) having NAD glycohydrolase activity that breaks N&AD down to nicotinamide and adenosine diphosphoribose (3). The administration of low levels of nicotinate to mice results in a marked increase in hepatic nicotinamide levels (4) presumably from NAD via NAD glycohydrolase.…”

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Effect of Hyperphysiological Levels of Hexestrol on the Hepatic Metabolism of Nicotinate in the Mouse

Dietrich¹,

Franklin²,

Farinas³

1970

Experimental Biology and Medicine

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Nicotinate is readily converted to NAD in animal tissues. The pathway involves nicotinate mononucleotide and nicotinate adenine dinucleotide as intermediates ( 1, 2 ) . Animal tissue also contains enzyme (s) having NAD glycohydrolase activity that breaks N&AD down to nicotinamide and adenosine diphosphoribose (3). The administration of low levels of nicotinate to mice results in a marked increase in hepatic nicotinamide levels (4) presumably from NAD via NAD glycohydrolase. This observation that nicotinate appears to be a more efficient precursor of hepatic nicotinamide than nicotinamide itself motivated us to explore the matter further. The results presented here indicate that hyperphysiological levels of hexestrol cause a marked alteration in the means whereby nicotinate is converted to nicotinamide in mice.Materials and Methods. The C57 black male mice (25-35 g) received hexestrol or sesame oil intramuscularly as described in the tables. The 14C-nicotinate was administered by intravenous injection at the level indicakd. The animals were sacrificed by cervical rupture a t the time indicated, the livers immediately removed and dropped into a dry ice-acetone freezing mixture. Individual frozen livers were dropped into 3 ml of boiling 0.04 M potassium phosphate buffer, p H 5.4.After 1 min in a boiling water bath the samples were homogenized for 30 sec, cooled in an ice bath and centrifuged a t 21,OOOg for 15 min. Carrier NAD, nicotinamide, and nicotinate where then added to the supernatant fluid and aliquots were applied to sh,eets of 1This study was supported by Grants CA 04868 and AM 03049 and a Career Development Award Health Service 6) from the United States Public Whatman 3MM paper. The sheets were developed in either the isobutyrate-NHS solvent of Magasanik et al. (4), or in butanol saturated with water containing solid NH4HC03 ( 5 ) . The spots corresponding to NAD, nicotinamide, and nicotinate were cut out and quantitated for radioactivity (6).Results and Discussion. The intravenous administration of tracer amounts of I Tnicotinate (1.5-7.5 pg) (Table I, Fig. 1) results in the following events: (i) The intrahepatic levels of labeled nicotinate decreases rapidly during the first few minutes after intravenous injection. This is evident in the case of intraportal injection. The level of nicotinate then gradually increases at a linear rate during the experimental period (60 min). The rapid disappearance of labeled nicotinate from the liver under these conditions is in keeping with the findings of Ijichi ct al. (7).(ii) Hepatic NAD and nicotinamide are rapidly labeled, significant amounts of these labeled compounds appearing in less than 0.2 or 1 min in the cases of intraportal or tail vein administration, respectively. These latter data are illustrated in Fig. 1 where the percentage change in specific activity is plotted against time, employing the values obtained a t 1 min as 100%. One-min values of 4497 cpm/pmole of NAD and 575 cpm/pmole of nicotinamide were obtained upon administration of nicotinate-l*C via...

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