title: Pyridine nucleotide cycling and poly(ADP-ribose) synthesis in resting human lymphocytes.
abstract: NAD is a critical cofactor for the oxidation of fuel molecules. The exposure of human PBL to agents that cause DNA strand breaks to accumulate can deplete NAD pools by increasing NAD consumption for poly(ADP-ribose) formation. However, the pathways of NAD synthesis and degradation in viable PBL have not been carefully documented. The present experiments have used radioactive labeling techniques to trace the routes of NAD metabolism in resting PBL. The cells could generate NAD from either nicotinamide or nicotinic acid. PBL incubated with [14C]nicotinic acid excreted [14C]nicotinamide into the medium. Approximately 50% of a prelabeled [14C]NAD pool was metabolized during 6 to 8 hr in tissue culture. Basal NAD turnover was prolonged threefold to fourfold by 3-aminobenzamide (3-ABA), an inhibitor of poly(ADP-ribose) synthetase. Supplementation of the medium with 3-ABA also prevented the accelerated NAD degradation that ensued after exposure of PBL to deoxyadenosine plus deoxycoformycin at concentrations previously shown to cause DNA strand break accumulation. These results demonstrate that quiescent human PBL continually produce NAD and utilize the nucleotide for poly(ADP-ribose) synthesis.
mesh_terms: D003839:Deoxyadenosines / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009525:Niacin / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*
chemical_list: D003839:Deoxyadenosines; D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D009525:Niacin