Glutamate transport asymmetry in renal glutamine metabolism

Patsy Carter, Tomas C. Welbourne
1998 American Journal of Physiology. Endocrinology and Metabolism  
Carter, Patsy, and Tomas C. Welbourne. Glutamate transport asymmetry in renal glutamine metabolism. Am. J. Physiol. 274 (Endocrinol. Metab. 37): E877-E884, 1998.-D-Glutamate (Glu) was previously shown to block L-Glu uptake and accelerate glutaminase flux in cultured kidney cells [Welbourne, T. C., and D. Chevalier. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E367-E370, 1997]. To test whether D-Glu would be taken up by the intact functioning kidney and effect the same response in vivo, male
more » ... gue-Dawley rats were infused with D-Glu (2.6 µmol/min), and renal uptake of D-and L-Glu was determined from chemical and radiolabeled arteriovenous Glu concentration differences times renal plasma flow. The amount removed was then compared with that amount filtered to obtain the antiluminal contribution. In the controls, L-Glu uptake measured as net removal was 33% of the arterial L-Glu load and not different from that filtered, 27%; however, the unidirectional uptake was actually 58% of the arterial load, indicating that antiluminal uptake contributes at least half to the overall Glu consumption. Surprisingly, the kidneys showed a more avid removal of D-Glu, removing 73% of the arterial load, indicating uptake predominantly across the antiluminal cell surface. Furthermore, uptake of D-Glu was associated with a 55% reduction in L-Glu uptake, with the residual amount taken up equivalent to that filtered; D-Glu did not increase the excretion of the L-isomer. However, elevating plasma L-Glu concentration reduced uptake of the D-isomer, suggesting a shared antiluminal transporter. Thus there is an apparent asymmetrical distribution of the D-Glu transporter. Under these conditions, kidney cortex L-Glu content decreased 44%, whereas net glutamine (Gln) uptake increased sevenfold (170 Ϯ 89 to 1,311 Ϯ 219 nmol/min, P Ͻ 0.01) and unidirectional uptake nearly threefold (393 Ϯ 121 to 1,168 Ϯ 161 nmol/min, P Ͻ 0.05); this large Gln consumption was paralleled by an increase in ammonium production so that the ratio of production to consumption approaches 2, consistent with accelerated Gln deamidation and subsequent Glu deamination. These results point to a functional asymmetry (antiluminal vs. luminal) for Glu transporter activity, which potentially plays an important role in modulating Gln metabolism and renal function. glutamate isomers; metabolic regulation; cellular acidosis; L-glutamate and L-[ 14 C]glutamine uptake; antiluminal glutamate uptake D-GLUTAMATE enhances glutamine utilization and ammonium and alanine production in cultured kidney cells by blocking L-glutamate uptake and decreasing cellular L-glutamate levels (27). Because glutamine is a major fuel for most cells (14, 25) as well as a source of metabolically generated base in the kidneys (4), regulation of this pathway is of considerable interest. In this regard, L-glutamate has long been recognized as a competitive inhibitor of the phosphate-dependent glutaminase reaction (8, 11, 23), the first committed step in Values are means Ϯ SE; n ϭ 4 for time control and n ϭ 3 for D-Glu infusion. Measurements were made over 15-30 min of infusion. Gln Syn, Gln formed as difference between UDU and Net. Renal plasma flows were 8 Ϯ 2 and 13 Ϯ 2 ml/min, P Ͻ 0.05. See Tables 1-3 for abbreviations. * Different from time control, P Ͻ 0.05.
doi:10.1152/ajpendo.1998.274.5.e877 fatcat:xigykm6okjhibjmefxj4x4e2am