Response of kynurenine pathway enzymes to pregnancy and dietary level of vitamin B-6.
The kynurenine pathway of tryptophan metabolism produces several neuroactive metabolites including 3-hydroxykynurenine, kynurenic acid, and quinolinic acid. This pathway is sensitive to reductions in vitamin B-6 availability because two key enzymes, kynurenine aminotransferase (KAT) and kynureninase (KYNase), require pyridoxal 5'-phosphate. During pregnancy abnormal concentrations of kynurenine metabolites are also found. We measured the effects of pregnancy and vitamin B-6 availability on KAT and KYNase in liver. DBA/2Ibg and A/Ibg mice were fed diets containing 0.25, 0.5, 2.0, 3.6, or 7.0 mg/kg pyridoxine-HCl (PN-HCl) for 4 weeks. Mitochondrial KAT and cytosolic KYNase were measured in control mice and pregnant mice on gestational days 16-18. The response of the two inbred strains was similar throughout. There were no marked alterations in KAT activity as a function of diet or pregnancy. In contrast, KYNase activities were significantly reduced by dietary restriction of vitamin B-6, and pregnant mice had significantly lower activity than nonpregnant controls for all but the highest dietary level of PN-HCl. These data show that pregnancy has a more pronounced effect on KYNase activity than vitamin B-6 restriction, and that the effects of pregnancy and diet are additive. The alteration in the kynurenine pathway in pregnancy is due to a reduction in KYNase activity, which is resistant to alleviation by vitamin B-6 supplementation.
van de Kamp
J L
JL
Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0447, USA.
Smolen
A
A
D000818:Animals; D004032:Diet; D005260:Female; D006867:Hydrolases / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008190:Lyases; D051379:Mice; D008805:Mice, Inbred A; D008811:Mice, Inbred DBA; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism / Q000502:physiology*; D011736:Pyridoxine / Q000494:pharmacology*; D000637:Transaminases / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D007737:Kynurenine; D014364:Tryptophan; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D006867:Hydrolases; C021480:kynureninase; D008190:Lyases; D011736:Pyridoxine