Abstract:
:Extracellular nicotinamide is well recognized as the primary precursor to the cellular synthesis of NAD. NAD is a pivotal molecule in regulating the energy and redox potentials of cells via synthesis of ATP and NAD(P)/NAD(P)H ratios. NAD turnover in cells is very rapid due to NAD catabolism via ADP-ribosylation reactions. These facts suggest that the cellular uptake and transport of nicotinamide may not be a passive process but a highly regulated cellular event. We have utilized radiometric procedures to characterize the uptake of [14C]nicotinamide in human leukemic K-562 cells. At physiologically relevant doses of nicotinamide (< 100 microM), the uptake was saturable with a Km of 2.3 +/- 1.0 microM and a Vmax of about 1.5 +/- 0.5 pmol/10(6) cells/min. Kinetic studies revealed that nicotinamide was first taken up intracellularly and then immediately converted to NAD and 1-methyl nicotinamide. All of the nicotinamide taken up into the cell was bound tightly to plasma membranes (25,000 g pellet) with Kd values between 3.2 and 12.7 microM and a Bmax of 1.56 pmol/10(6) cells. The specificity of nicotinamide binding was demonstrated by competitive inhibition experiments using NAD analogs, nicotinamide derivatives, and agonists or antagonists of plasma membrane receptors. We conclude that there is specific binding of nicotinamide, followed by intracellular uptake and immediate synthesis to NAD.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Olsson A,Olofsson T,Pero RWdoi
10.1016/0006-2952(93)90270-7subject
Has Abstractpub_date
1993-03-24 00:00:00pages
1191-200issue
6eissn
0006-2952issn
1873-2968pii
0006-2952(93)90270-7journal_volume
45pub_type
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