EFFECT OF ACETOACETATE AND Β-Hydroxy-Butyrate ON THE BIOSYNTHESIS OF NIACIN FROM TRYPTOPHAN

Effect of Acetoacetate on Liver and Blood Pyridine Nucleotides in Rats

“…In view of these observations it appears possible that acetoacetate may lead to decreased biogenesis of PN and this may be a con tributing factor to the lowered value of PN in tissues of rats fed tryptophan and given acetoacetate injections (Table 2). Lower values of PN in liver and blood of rats administered acetoacetate (Table 3) may be to some extent, a reflection of depletion of niacin observed previously (4) in such rats. It has been reported that, proper utilization of lactic acid which requires coenzyme I is arrested in animals treated with acetoacetate (10).…”

“…MORRISON et al (9) have suggested that increase in liver and blood PN in response to doses of tryptophan and niacin is due to the increased catabolism of tryptophan to niacin and the metabolism of niacin to niacinamide and N1-methylniacinamide with NAD as an intermediate. It has been reported from this laboratory that acetoacetate causes decreased biosynthesis of niacin from tryptophan, resulting in diminished urinary excretion of niacin and N1 -methylniacinamide in rats (4). In view of these observations it appears possible that acetoacetate may lead to decreased biogenesis of PN and this may be a con tributing factor to the lowered value of PN in tissues of rats fed tryptophan and given acetoacetate injections (Table 2).…”

“…FEIGEL SON and coworkers (3) also reported both niacin and tryptophan to be effective precursors of liver pyridine nucleotides. It was observed in this laboratory that acetoacetate administration causes an impairment in the biosynthesis of niacin from tryptophan and leads to depletion of urinary and tissue niacin in rats (4). Further, acetoacetate-treated rats were found to excrete abnormal quantities of various tryptophan metabolites in their urine on tryptophan ingestion (5) and were also found to exhibit abnormally high activity of hepatic picolinic carbo xylase and lower than normal activity of hepatic kynureninase (6).…”

Comparison of the Activity of the Tryptophan-NAD Pathway between Rats Fed a Fat-free Diet and a Fat Diet

“…On the other hand, Shastri et al 8 ) reported that the intraperitoneal injection of sodium 3-hydroxybutyrate or sodium acetoacetate, which is an intermediate in fatty acid degradation, into young rats fed a 20% casein and 10% oil diet for 60 days (the starting dose was 50 mg/kg body weight and this was increased by 50 mg/kg every 15 days) led to lower urinary excretion of N 1 _ methylnicotinamide. Later, they reported that the livers of rats treated with acetoacetate for 90 days had abnormally high ACMSDase values.2 3 ) On the contrarY,Ng et al 24 ) reported that overloading of acetoacetate in the perfusate interfered with the flow of tryptophan into the glutaric acid pathway in isolated perfused rat liver.…”

Increased Conversion of Tryptophan to Nicotinamide in Rats by Dietary Valproate

“…[21][22][23][24][25][26][27][28][29][30] Shin et al 31) have reported that the administration to rats of peroxisome proliferators increased the liver NAD concentration by inhibiting liver -amino--carboxymuconate-"-semialdehyde decarboxylase (ACMSD). Our experience of measuring the ACMSD activity has taught us the difficulty of measuring the extent of inhibition by the method used by Shin et al 31) We were however interested in the result that the administration of valproic acid (VPA), one of the peroxisome proliferators, increased the liver NAD concentration, 31) because there have been several reports of such short-chained fatty acids [32][33][34] as sodium acetate, sodium 3-hydroxybutyrate, sodium acetoacetate and dietary fat [35][36][37] affecting metabolism on the Trp degradation pathway. VPA is a short-chain, branched fatty acid widely used by humans as an anticonvulsant in the treatment of epilepsy, anorexia nervosa, panic attack, anxiety disorder, post-traumatic stress disorder, migraine and bipolar disorder, as well as other psychiatric conditions requiring the administration of a mood stabilizer.…”