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The Journal of biological chemistry1983; 258(24); 15071-15078;

The mechanism of Na+-L-lactate cotransport by brush-border membrane vesicles from horse kidney. Analysis by isotopic exchange kinetics of a sequential model and stoichiometry.

Abstract: The present study determines the characteristics of isotopic Na and lactate exchange under equilibrium conditions in horse kidney brush-border membrane vesicles. The influence of one solute (Na+ or lactate) on the isotopic exchange of the co-transported species (lactate or Na) was analyzed in detail. Analysis of the data suggests that Na and lactate interact sequentially with the carrier. The observed apparent symmetry between the activating effect of low Na concentrations and the inhibiting effect of high Na concentrations on the lactate exchange process suggests that the carrier functions according to a glide symmetry model where the two solutes bind to the carrier according to an iso-ordered Bi Bi process. This conclusion is strengthened by the properties of the 22Na exchange process catalyzed by the lactate carrier. Direct measurement under equilibrium conditions of the coupled Na+/lactate transport indicated a stoichiometry of 2:1. These data, along with those obtained in a previous study (Mengual R., and Sudaka P. (1983) J. Membr. Biol. 71, 163-171) allow us to propose a mechanism for the Na+-lactate cotransport, involving a transport system that functions according to an iso-ordered Bi Bi process where binding and debinding of Na+ occur first, followed by the lactate molecule.
Publication Date: 1983-12-25 PubMed ID: 6654905
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  • Journal Article

Summary

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The research investigates the interplay between sodium (Na) and lactate in horse kidney brush-border membrane vesicles. By examining the interaction between these two substances within a brush-border membrane, the researchers propose a mechanism for Na-lactate cotransport and assert a 2:1 stoichiometry.

Isotopic Exchange of Na and Lactate Under Equilibrium Conditions

  • Key features of isotopic Na and lactate exchange under equilibrium conditions in horse kidney brush-border membrane vesicles were thoroughly examined.
  • The equilibrium conditions were maintained in order to accurately determine the rate and extent of Na and lactate exchange.
  • Such an approach offered a fair understanding of the detailed physiological interactions between these two vital substances.

Influence of One Solute on the Isotopic Exchange of the Other

  • The study delves into understanding how the presence and concentration of one solute (sodium or lactate) can affect the isotopic exchange of the other within the brush-border membrane of the horse’s kidney.
  • The assessment provides crucial detail on how each co-transported species (lactate or sodium) may potentially influence the exchange of their counterpart.
  • These findings can potentially deepen our understanding of the intricate cotransport process of these two substances in the kidney.

Glide Symmetry Model and Iso-Ordered Bi Bi Process

  • The analysis demonstrated an apparent symmetry between the activating effect of low sodium concentrations and the inhibiting effect of high sodium concentrations on the lactate exchange process.
  • The researchers believe this timing and order of interactions suggest that the carrier operates on a glide symmetry model. Here, both solutes, sodium and lactate, bind to the carrier in a stepwise manner in an iso-ordered Bi Bi process.
  • This binding pattern has sodium binding and debinding first, followed by lactate. This finding reinforces the idea that the sodium-lactate cotransport system functions according to an iso-ordered Bi Bi mechanism.

Coupled Na+/lactate Transport Stoichiometry

  • This research also measured the stoichiometry of the coupled sodium-lactate transport under equilibrium conditions.
  • The results indicate a stoichiometry of 2:1, implying that two sodium ions are transported for every one lactate molecule.
  • This compartmentalized and numerically balanced exchange demonstrates a systematic method of Na-lactate cotransport, which might help in making accurate predictions in pharmacokinetics and medical diagnosis.

Proposition of a Mechanism for Na-Lactate Cotransport

  • Based on these findings and the data from a previous study, the researchers propose a mechanism for Na-lactate cotransport.
  • This mechanism implies a transport system that functions according to an iso-ordered Bi Bi process, where Na binds and debinds first, followed by lactate.
  • Such an established model of interaction and exchange provides a more advanced understanding of vital physiology related to renal processes and might contribute to the development of treatment strategies for kidney-related conditions.

Cite This Article

APA
Mengual R, Leblanc G, Sudaka P. (1983). The mechanism of Na+-L-lactate cotransport by brush-border membrane vesicles from horse kidney. Analysis by isotopic exchange kinetics of a sequential model and stoichiometry. J Biol Chem, 258(24), 15071-15078.

Publication

ISSN: 0021-9258
NlmUniqueID: 2985121R
Country: United States
Language: English
Volume: 258
Issue: 24
Pages: 15071-15078

Researcher Affiliations

Mengual, R
    Leblanc, G
      Sudaka, P

        MeSH Terms

        • Animals
        • Biological Transport, Active
        • Horses
        • Kidney Cortex / ultrastructure
        • Kinetics
        • Lactates / metabolism
        • Lactic Acid
        • Mathematics
        • Microvilli / metabolism
        • Sodium / metabolism

        Citations

        This article has been cited 6 times.
        1. Jørgensen KE, Sheikh MI. Renal transport of monocarboxylic acids. Heterogeneity of lactate-transport systems along the proximal tubule.. Biochem J 1984 Nov 1;223(3):803-7.
          doi: 10.1042/bj2230803pubmed: 6508742google scholar: lookup
        2. Siebens AW, Boron WF. Effect of electroneutral luminal and basolateral lactate transport on intracellular pH in salamander proximal tubules.. J Gen Physiol 1987 Dec;90(6):799-831.
          doi: 10.1085/jgp.90.6.799pubmed: 3440860google scholar: lookup
        3. Edlund GL, Halestrap AP. The kinetics of transport of lactate and pyruvate into rat hepatocytes. Evidence for the presence of a specific carrier similar to that in erythrocytes.. Biochem J 1988 Jan 1;249(1):117-26.
          doi: 10.1042/bj2490117pubmed: 3342001google scholar: lookup
        4. Poole RC, Halestrap AP. Reconstitution of the L-lactate carrier from rat and rabbit erythrocyte plasma membranes.. Biochem J 1988 Sep 1;254(2):385-90.
          doi: 10.1042/bj2540385pubmed: 3178766google scholar: lookup
        5. Mengual R, Claude-Schlageter MH, Poiree JC, Yagello M, Sudaka P. Characterization of sodium and pyruvate interactions of the two carrier systems specific of mono- and di- or tricarboxylic acids by renal brush-border membrane vesicles.. J Membr Biol 1989 Jun;108(3):197-205.
          doi: 10.1007/BF01871734pubmed: 2778796google scholar: lookup
        6. Ullrich KJ, Papavassiliou F. Contraluminal transport of small aliphatic carboxylates in the proximal tubule of the rat kidney in situ.. Pflugers Arch 1986 Nov;407(5):488-92.
          doi: 10.1007/BF00657505pubmed: 2431382google scholar: lookup