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KMID : 0376219670040010057
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Chonnam Medical Journal
1967 Volume.4 No. 1 p.57 ~ p.70
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Metabolism of Nicotinic Acid and Nicotinamide in Rabbit Brain Cortex in vitro
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Abstract
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1. Incubation at 37°C of rabbit brain-cortex slices in Krebs-Ringer phosphate medium containing glucose and 14C-labeled nicotinic acid and nicotinamide resulted in the uptake of the labeled vitamins by the tissue. The concentration in the tissue cell water of the labeled vitamins increased with increase of external labeled vitamin concentration in an approximately linear manner. However, the uptake of labeled nicotinic acid and labeled nicotinamide(1.5 mM)was not influenced by the presence of high concentration(10 mm) of nonradioactive nicotinamide and nicotinic acid, respectively. The uptake of nicotinic acid increased almost linearly up to 3 hours incubation whereas that of nicotinamide declined rapidly after 2 hours incubation.
2. In the absence of glucose or in the presence of 2,4 dinitrophenbol (0.05 mM)and of sodium azide(2 mM), there was a fall in the uptake of the labeled vitamins by brain-cortex slices, the fall of nicotinic acid being more pronotiri ced--than that of nicotinamide. In contrast, the presence of high concentration of KCl(96.3 mM) in the medium resulted in one and one half-fold increase in the uptake of both vitamins. The addition of ouabain(0.1-0.2 mM), which did not elicit any influence on the uptake of both vitamins in the presence of normal concentration(4.8 mM) of KC1-in the medium, markedly depressed the increase in the uptake of both vitamins that otherwise occurred when high concentration of KC1(96.3 mM) was added to the medium.
3. The addition of isonicotinyl hydrazide(2mM)caused a marked inhibition of the uptake of both vitamins, and the presence of chlorpromazine(l mM)and of sodium Amytal(l mM)also led to depression of the uptake of nicotinic acid alone, the uptake of nicotinamide being not influenced at all, and their inhibitory effects became more pronounced in the high KCI medium.
4. Of the radioactivity of nicotinic acid taken up in the brain tissue, approximately 20 to 30% was recovered in NAD and various pyridine riboside and ribonucleotide intermediates of NAD biosynthesis and breakdown. The facts indicate the simultaneous occurrence of NAD biosynthesis and breakdown. The radioactivity of nicotinamide-14C was also recovered in part in NAD and other pyridine compounds. However, since the time course of the incorporation of nicotinic acid and nicotinamide into NAD and other pyridine compounds was differed with each vitamin, it is suggested that the manner by which nicotinic acid is incorporated into NAD is different from that of nicotinamide.
5. From these results it might be concluded that the uptake of nicotinic acid and nicotinamide by rabbit brain cortex slices is energy dependent and K ion-sensitive process, and that a portion of the nicotinic acid and nicotinamide taken up by the tissue is converted to NAD in different manners with the concomitant active breakdown of NAD.
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