Lipid metabolism was studied in experimental uremia. Uremic (U) rats were compared with sham-operated, pair-fed (PF) controls and with ad-lib-fed (AL) controls. In U animals, fasting glucose concentrations were normal, immunoreactive serum insulin (IRI) levels were decreased, and immunoreactive glucagon levels were increased. A significant increase in the serum concentration of all lipid classes was observed: triglycerides were elevated 10-fold above the values in PF and AL controls; phospholipids, twofold; total cholesterol, threefold; and free cholesterol, sixfold. Cholesterol concentration was increased in beta- and pre-beta-lipoproteins and even more so in alpha- and pre-alpha-lipoproteins. There was an increase in the ratio of free cholesterol/total cholesterol. The fatty acid composition of serum lipoproteins was unchanged. Concomitantly, in liver tissue, there was no change in lipid content (triglyceride, cholesterol) and fatty acid composition. These findings argue against glucose- or insulin-mediated changes in hepatic de novo fatty acid synthesis, chain elongation, or poly-desaturation. In U animals, the HMG-CoA-reductase activity of liver microsomes was slightly, but not significantly, reduced as was tritiated water incorporation into cholesterol in isolated perfused liver preparations. In adipose tissue, there was a decrease in triglyceride content. The results provide evidence against insulin-mediated hepatic overproduction as a major cause of hyperlipoproteinemia in this model of experimental renal insufficiency and point to peripheral under-utilization of lipoproteins.

Isolated perfused rat liver incorporates nicotinamide a t a concentration of 10 pM into NAD via nicotinamide mononucleotide. A deamidation of nicotinamide could not be demonstrated.Evidence is presented which indicates that the exchange reaction catalyzed by NAD glycohydrolase is not involved in the uptake of nicotinamide into NAD.At the concentrations used, the rate of the incorporation of nieotinamide into NAD is about 40°/, of the incorporation rate observed with nicotinic acid.Results obtained after perfusion with [14C]nicotinic acid support the concept of an intracellular pyridine nucleotide cycle. However, in contrast to the general opinion, our results demonstrate that in rat liver nicotinamide generated by NAD breakdown is not deamidated but reutilized via nicotinamide mononucleotide.After perfusion with 0.1 mM ['4C]nicotinamide for 2.5 h, less than 2O/, of the total radioactivity is excreted into the bile. The same value is obtained after perfusion with 50 pM [14C]nicotinic acid. From these results it is concluded that the excretion of nicotinamide by the liver and the subsequent deamidation within the intestinal tract which have been considered important in the utilization of nicotinamide by the liver, are without biological relevance a t normal nicotinamide concentrations.The biosynthesis of NAD in mammalian liver (Fig.l) way is not biologically relevant to mammalian liver, and it is believed that nicotinamide has t o be deamidated to nicotinic acid before entering the biosynthetic ATP PPi r Nem NAD

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