Tryptophan metabolism by the isolated rat liver cells--effects of leucine and its metabolites.
1. The effects of leucine and its metabolites, such as alpha-ketoisocaproate and ketone bodies, on the metabolic fluxes of tryptophan were investigated in isolated rat liver cells using [benzene ring-U-14C]- or [methylene-14C]-tryptophan. 2. Tryptophan metabolized through the kynureninase flux decreased while that metabolized to acetyl CoA remained unchanged in the presence of leucine or its metabolites. Accordingly an amount of tryptophan metabolized through the quinolinate-NAD pathway, which was estimated by subtracting an amount of tryptophan metabolized via the acetyl CoA flux from that via the kynureninase flux, was decreased in the presence of leucine or its metabolites. 3. Less quinolinate accumulated during incubation with metabolites of leucine, however, the amount was still sufficient to saturate quinolinate phosphoribosyltransferase (EC 2.4.2.19). 4. Leucine and its metabolites added in vitro at 1 mM level did not inhibit quinolinate phosphoribosyltransferase activity in rat liver homogenate. 5. The results indicate that a decrease in NAD biosynthesis from tryptophan caused by metabolites of leucine in the isolated rat liver cells was neither due to insufficient supply of quinolinate nor to direct inhibitory effect on quinolinate phosphoribosyltransferase.
Kiyohara
Y
Y
School of Pharmacy, Kobe-Gakuin University, Japan.
Shirasawa
K
K
Shin
M
M
Sano
K
K
Umezawa
C
C
D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000096:biosynthesis*; D010430:Pentosyltransferases / Q000378:metabolism; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000378:metabolism*; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D000090:Acetoacetates; D007651:Keto Acids; D011805:Quinolinic Acids; D009243:NAD; C016635:acetoacetic acid; C013082:alpha-ketoisocaproic acid; D014364:Tryptophan; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid; D007930:Leucine