Effect of diet on the urinary excretion of hippuric acid and other dietary-derived aromatics in rat. A complex interaction between diet, gut microflora and substrate specificity.
1. A combined in vivo and in vitro study has been devised to investigate an observation, obtained by 1H NMR of urine, that Alp:AprSD (Wistar derived) rats kept under standard husbandry conditions did not excrete urinary hippuric acid (HA). meta-(hydroxyphenyl)-propionic acid ¿m-HPPA¿ was identified as the major aromatic component in urine samples lacking HA. 2. Examination of urine from Alp:APrSD and Zücker (obese negative) rats fed various diets showed that the lack of HA/presence of m-HPPA was due to diet and not to the strain of animal. This observation was reinforced by the demonstration that the administration of benzoic acid (BA) to rats not previously excreting urinary HA resulted in the return of this component to the urinary excretion profile. Thus rats receiving the standard diet were still capable of glycine conjugation. 3. Changing the diet of rats excreting m-HPPA led to the cessation of m-HPPA excretion and the return of HA urine excretion. Interestingly, switching back to the original diet did not cause the loss of HA and the re-emergence of m-HPPA. 4. In vitro studies on the two enzyme systems responsible for glycine conjugation (benzoyl CoA:synthetase and benzoyl CoA:glycine N-acyltransferase) in isolated liver mitochondria showed that m-HPPA did not inhibit either enzyme. However, m-HPPA was not found to be a substrate for the first reaction step explaining why it was found in the urine as the free acid and not as a glycine conjugate. 5. The absence and presence of m-HPPA and hippuric acid is suggested to be due to a combination of differences in dietary precursors of substrates for glycine conjugation and a dietary dependent redistribution of the intestinal microflora responsible for breakdown of plant phenolics and aromatic amino acids. Taken collectively this study emphasises how a simple diet change can cause a profound change in metabolism.
Phipps
A N
AN
ZENECA Pharmaceuticals, Safety of Medicines Department, Cheshire, UK.
Stewart
J
J
Wright
B
B
Wilson
I D
ID
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003066:Coenzyme A Ligases / Q000378:metabolism; D004032:Diet; D005998:Glycine / Q000378:metabolism; D006626:Hippurates / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker
D006626:Hippurates; D000217:Acyltransferases; C002807:benzoyl-CoA-glycine N-acyltransferase; D003066:Coenzyme A Ligases; C055455:benzoate coenzyme A ligase; C030514:hippuric acid; D005998:Glycine