Metabolism of Niacin and Niacinamide in Perfused Rat Intestine

Abstract

The metabolism of [¹⁴C]nicotinic acid and [¹⁴C]nicotinamide by perfused rat intestine was studied by analyzing the ¹⁴C-products formed at various time intervals after these substrates were administered intravascularly or intralumenally. Intermediates in the Preiss-Handler pathway contained isotope when [¹⁴C]nicotinic acid was administered by either route. Large amounts of isotope in niacinamide and some in nicotinamide mononucleotide (NMN) were also found indicating substantial NAD-glycohydrolase activity in this intestinal preparation. The products from [¹⁴C]nicotinamide also included the metabolites of nicotinic acid, due to deamidation of the substrate in the lumen when the exposure was prolonged. In short term studies the amide was absorbed rapidly by simple diffusion with little hydrolysis to nicotinic acid. The primary labeled form found in the perfusate when [¹⁴C]nicotinic acid was administered via the lumen for both recirculating and one pass perfusions was unchanged nicotinic acid. The primary forms found in the perfusate when the amide was given were both the amide and the acid for both one pass and for recirculating experiments. The rapid transport of nicotinamide from the lumen to the perfusate and the lack of ¹⁴C-metabolites of nicotinic acid in the intestinal tissue following intralumenal injection of [¹⁴C]nicotinamide in the living animal suggest that deamidation in the digestive tract is not a major fate of physiological quantities of niacinamide.