Regulatory responses to an oral D-glutamate load: formation of D-pyrrolidone carboxylic acid in humans

Am J Physiol Endocrinol Metab. 2001 Feb;280(2):E214-20. doi: 10.1152/ajpendo.2001.280.2.E214.


Previously published studies have shown D-glutamate to be the most potent natural inhibitor of glutathione synthesis known, yet how D-glutamate is handled in humans is unknown. Therefore, we administered an oral D-glutamate load to four healthy volunteers and monitored the plasma D-glutamate concentration and excretion over a 3-h postload period. Compared with time controls, the plasma D-glutamate concentration increased 10-fold in the 1st h and then reached a plateau over the remaining time course. In contrast, plasma D-pyrrolidone carboxylic acid increased progressively throughout the 3-h time course to a level 10-fold higher than the D-glutamate plasma concentration. Excretion of D-glutamate progressively increased despite a constant filtered D-glutamate load rising from only 5 to 95% of the filtered amount. Excretion of D-pyrrolidone carboxylic acid increased with the rise in filtered load without significant reabsorption. The amount of D-pyrrolidone carboxylic acid excreted over the 3-h time course was 10 times the amount excreted as D-glutamate and accounted for almost 20% of the administered D-glutamate. These findings indicate that plasma D-glutamate concentration is tightly regulated through two mechanisms: 1) the transport into cells and metabolic conversion to D-pyrrolidone carboxylic acid and excretion, and 2) the enhancement of D-glutamate clearance by the kidneys.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Oral
  • Adult
  • Glutamic Acid / blood
  • Glutamic Acid / pharmacokinetics*
  • Glutamic Acid / urine
  • Humans
  • Male
  • Pyrrolidonecarboxylic Acid / blood
  • Pyrrolidonecarboxylic Acid / metabolism*
  • Pyrrolidonecarboxylic Acid / urine
  • Time Factors


  • Glutamic Acid
  • Pyrrolidonecarboxylic Acid