Skip to main content
Log in

Kinetic characteristics of folate binding to rat renal brush border membrane in chronic alcoholism

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The binding of folic acid to the plasma membrane is an important event for its reabsorption and conservation by renal epithelium. We studied [3H] folic acid binding to the renal cortical brush border membrane vesicles (BBMV) in rats after 12 weeks of chronic ethanol ingestion. Our results demonstrated that after chronic ethanol intake, the binding of folic acid to the membrane vesicles: (1) was decreased by a mechanism that decreased Bmax without affecting Kd, (2) was insensitive to Na+ ions in the medium (3) behaved differently to divalent cations in the medium in contrast to control group. However under such conditions there was no significant effect of ethanol on pH optimum of the process. Binding was reduced at pH less than 6 but there was no effect of ethanol on binding in pH range from 6 to 8. Increasing the osmolarity at pH 5.5 had no effect on the binding of folate to BBMV, thus confirming that the observed changes in Bmax values were due to site-specific binding in the two groups. Moreover, ethanol does not impart its effect on involvement of sulfhydryl group at the binding site of folate transport system. These findings highlight the possible mechanism of perturbed renal conservation of folate during chronic alcoholism. (Mol Cell Biochem xxx: 219–225, 2005)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Villanueva J, Ling EH, Chandler CJ, Halsted CH: Membrane and tissue distribution of folate binding protein in pig. Am J Physiol 275: R1503–R1510, 1998

    PubMed  CAS  Google Scholar 

  2. Birn H, Slug J, Christensen EI: Internalization and intracellular transport of folate binding protein in rat kidney proximal tubule. Am J Physiol 264: C302–C310, 1993

    PubMed  CAS  Google Scholar 

  3. Williams WM, Huang KC: Renal tubular transport of folic acid and methotrexate in the monkey. Am J Physiol 242: F484–F490, 1982

    PubMed  CAS  Google Scholar 

  4. McMartin KE, Shiao CQ, Collins TD, Rodetzki HM: Acute ethanol ingestion by humans and subacute treatment of rats increase urinary folate excretion. Alcohol 2: 473–477, 1985

    Article  PubMed  CAS  Google Scholar 

  5. McMartin KE, Collins TD, Shiao CQ, Vidrine L, Rodetzki HM: Study of dose dependence and urinary folate excretion produced by ethanol in humans and rats. Alcohol Clin Exp Res 10: 419–424, 1986

    PubMed  CAS  Google Scholar 

  6. McMartin KE, Timothy DC, Bernard HE, Tamaca F, William RB, Lee BF: Effects of chronic ethanol and diet treatment on urinary folate excretion and development of folate deficiency in the rat. J Nutr 119: 1490–1497, 1989

    PubMed  CAS  Google Scholar 

  7. Eisenga BH, Collins TD, McMartin KE: Differential effects of acute ethanol on urinary excretion of folate derivatives in the rat. J Pharmacol Exp Ther 248: 916–922, 1989

    PubMed  CAS  Google Scholar 

  8. Van HCM, Ling EH, Halsted CH: Folate binding protein: molecular characterization and transcript distribution in pig liver, kidney and jejunum. Biochem J 319: 725–729, 1996

    Google Scholar 

  9. Bhandari SD, Fortney T, McMartin KE: Analysis of the pH dependence of folate binding and transport by rat kidney brush border membrane vesicles. Proc Soc Exp Biol Med 196: 451–456, 1991

    PubMed  CAS  Google Scholar 

  10. Villanueva J, Chandler CJ, Shimasaki N, Nakamura MT, Tang A, Phinney SD, Halsted CH: Effects of ethanol feeding on liver, kidney and jejunal membranes in micropigs. Hepatology 19: 1229–1240, 1994

    Article  PubMed  CAS  Google Scholar 

  11. Bhandari SD, Joshi SK, McMartin KE: Folate binding and transport by rat kidney brush border membrane vesicles. Biochim Biophys Acta 937: 211–218, 1988

    PubMed  CAS  Google Scholar 

  12. Balinska M, Nimec Z, Galivan J: Characteristics of methotrexate polyglutamate formation in cultured hepatic cells. Arch Biochem Biophys 216: 466–476, 1982

    Article  PubMed  CAS  Google Scholar 

  13. Beck JC, Sacktor B: The sodium electrochemical potential mediated uphill transport of d-glucose in renal brush border membrane vesicles. J Biol Chem 253: 5531–5535, 1978

    PubMed  CAS  Google Scholar 

  14. Bergmeyer HU: Alkaline phosphatase from calf intestine. In: Methods of Enzymatic Analysis, 2nd edn. Academic press, New York, 1974, pp 496–498

    Google Scholar 

  15. Quigley JP, Gotterer GS: Distribution of Na+–K+ stimulated ATPase in rat intestinal mucosa. Biochim Biophys Acta 173: 456–468, 1969

    PubMed  CAS  Google Scholar 

  16. Selhub J, Rosenberg IH: Folate transport in isolated brush border membrane vesicles from rat intestine. J Biol Chem 256: 4489–4493, 1981

    PubMed  CAS  Google Scholar 

  17. Scatchard G: The attraction of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672, 1949.

    CAS  Google Scholar 

  18. Muldoon RT, McMartin KE: Ethanol acutely impairs the renal conservation of 5-methyltetrahydrofolate in the isolated perfused rat kidney. Alcohol Clin Exp Res 18: 333–339, 1994

    PubMed  CAS  Google Scholar 

  19. Kaur J: Chronic ethanol feeding affects intestinal mucus lipid composition and glycosylation in rats. Ann Nutr Metab 46: 38–44, 2002

    Article  PubMed  CAS  Google Scholar 

  20. Eisenga BH, Collins TD, McMartin KE: Effects of acute ethanol on urinary excretion of 5-methyltetrahydrofolic acid and folate derivatives in the rat. J Nutr 119: 1498–1505, 1989

    PubMed  CAS  Google Scholar 

  21. Ross DM, McMartin KE: Effect of ethanol on folate binding by isolated rat renal brush border membranes. Alcohol 13: 449–454, 1996

    Article  PubMed  CAS  Google Scholar 

  22. Koeppen B, Giebisch G, Malnic G: Mechanism and regulation of renal tubular acidification. In: DW Seldin, G Giebisch (eds.). The Kidney: Physiology and Pathophysiology. Raven, New York, 1985, pp 1491–1525

    Google Scholar 

  23. Said HM, Strum WB: A pH-dependent, carrier-mediated system for transport of 5-methyltetrahydrofolate in rat jejunum. J Pharmacol Exp Ther 226: 95–99, 1983

    PubMed  CAS  Google Scholar 

  24. Reisenauer AM, Chandler CJ, Halsted CH: Folate binding and hydrolysis by pig intestinal brush border membranes. Am J Physiol 251: G481–G486, 1986

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jyotdeep Kaur.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hamid, A., Kaur, J. Kinetic characteristics of folate binding to rat renal brush border membrane in chronic alcoholism. Mol Cell Biochem 280, 219–225 (2005). https://doi.org/10.1007/s11010-005-0166-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-0166-0

Keyword

Navigation