Regulatory responses to an oral D-glutamate load: formation of D-pyrrolidone carboxylic acid in humans.
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.
Raj
D
D
Department of Medicine, Louisiana State University Health Science Center, Shreveport, LA 71130, USA.
Langford
M
M
Krueger
S
S
Shelton
M
M
Welbourne
T
T
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D018698:Glutamic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors
D018698:Glutamic Acid; D011761:Pyrrolidonecarboxylic Acid