Skip to main content
SpringerLink
Log in

Gymnemic acid interacts with mammalian glycerol-3-phosphate dehydrogenase

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

Abstract

In a previous study, we found interaction of gymnemic acid (GA) with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis. We now examined interaction of GA with glycolytic and related enzymes. We found that (1) GA induced a band smearing of glycerol-3-phosphate dehydrogenase (G3PDH) as well as that of GAPDH in SDS-PAGE, (2) GA diminished the G3PDH band detected by an antibody to phosphoserine, and (3) GA inhibited the G3PDH activity. The GA-induced smearing of the G3PDH band was diminished by prior incubation of GA with γ-cyclodextrin. GA gave no effects on the electrophoretic and phosphoserine bands of other glycolytic enzymes. NAD and NADH diminished the GA-induced smearing of the G3PDH and GAPDH bands in different concentration-dependent manner. Pretreatment of G3PDH with heated SDS-containing buffer or pretreatment with hydroxylamine diminished the GA-induced smearing of G3PDH. Deacylation of GA by alkaline hydrolysis diminished the smearing of G3PDH band, thereby indicating that the acyl moieties of GA were necessary for the GA-induced smearing of G3PDH. These results indicated the interaction of GA with G3PDH, an enzyme involved in glycerol metabolism. These studies suggest that GA may have some pharmacological activities including antidiabetic activity and lipid lowering effects via interaction with GAPDH and G3PDH.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Warren RM, Pfaffmann C (1959) Suppression of sweet sensitivity by potassium gymnemate. J Appl Physiol 14:40–42

    PubMed  CAS  Google Scholar 

  2. Kurihara Y (1969) Antisweet activity of gymnemic acid A1 and its derivatives. Life Sci 8:537–543

    Article  PubMed  CAS  Google Scholar 

  3. Yoshikawa M, Murakami T, Matsuda H (1997) Medicinal foodstuffs. X. Structures of new triterpene glycosides, gymnemosides-c, -d, -e, and -f, from the leaves of Gymnema sylvestre R. Br.: influence of gymnema glycosides on glucose uptake in rat small intestinal fragments. Chem Pharm Bull 45:2034–2038

    PubMed  CAS  Google Scholar 

  4. Hirata S, Abe T, Imoto T (1992) Effects of crude gymnemic acid on the oral glucose tolerance test in human being. J Yonago Med Assoc 43:392–396

    CAS  Google Scholar 

  5. Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I (2000) Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. J Asian Nat Prod Res 2:321–327

    Article  PubMed  CAS  Google Scholar 

  6. Izutani Y, Hirai H, Takei T, Imoto T, Ishijima S, Ohnishi M (2002) Studies on the proteins from fungiform papillae of bovine tongue: Glyceraldehyde-3-phosphate dehydrogenase is bound to gymnemic acid-coupling gel. J Biol Macromol 2:60–63

    CAS  Google Scholar 

  7. Izutani Y, Murai T, Imoto T, Ohnishi M, Oda M, Ishijima S (2005) Gymnemic acids inhibit rabbit glyceraldehyde-3-phosphate dehydrogenase and induce a smearing of its electrophoretic band and dephosphorylation. FEBS Lett 579:4333–4336

    Article  PubMed  CAS  Google Scholar 

  8. Sirover MA (1999) New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase. Biochim Biophys Acta 1432:159–184

    PubMed  CAS  Google Scholar 

  9. Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER (1983) Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre, R.Br. J Ethnopharmacol 7:205–234

    Article  PubMed  CAS  Google Scholar 

  10. Suttisri R, Lee I-S, Kinghorn AD (1995) Plant-derived triterpenoid sweetness inhibitors. J Ethnopharmacol 47:9–26

    Article  PubMed  CAS  Google Scholar 

  11. Fondy TP, Ross CR, Sollohub SJ (1969) Structural studies on rabbit muscle glycerol 3-phosphate dehydrogenase and a comparison of chemical and physical determinations of its molecular weight. J Biol Chem 244:1631–1644

    PubMed  CAS  Google Scholar 

  12. Crimmins DL, Mische SM (1995) Chemical cleavage of proteins in solution. In: Coligan JE, Dunn BM, Ploegh HL, Speicher DW, Wingfield PT (eds) Current protocols in protein science. John Wiley & Sons

  13. Izutani Y, Kanaori K, Imoto T, Oda M (2005) Interaction of gymnemic acid with cyclodextrins analyzed by isothermal titration calorimetry, NMR and dynamic light scattering. FEBS J 272:6154–6160

    Article  PubMed  CAS  Google Scholar 

  14. Persaud SJ, Al-Majed H, Raman A, Jones PM (1999) Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol 163:207–212

    Article  PubMed  CAS  Google Scholar 

  15. Luo H, Wang F, Imoto T, Hiji Y (2001) Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine. World J Gastroenterol 7:9–15

    PubMed  CAS  Google Scholar 

  16. Porchezhian E, Dobriyal RM (2003) An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and patents. Pharmazie 58:5–12

    PubMed  CAS  Google Scholar 

  17. Kimura I (2006) Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions. Yakugaku Zasshi 126:133–143

    Article  PubMed  CAS  Google Scholar 

  18. Luo H, Kashiwagi A, Shibahara T, Yamada K (2007) Decreased bodyweight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal. Mol Cell Biochem 299:93–98

    Article  PubMed  CAS  Google Scholar 

  19. Albina JE, Mastrofrancesco B, Reichner JS (1999) Acyl phosphatase activity of NO-inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH): a potential mechanism for uncoupling glycolysis from ATP generation in NO-producing cells. Biochem. J 341:5–9

    Article  PubMed  CAS  Google Scholar 

  20. Lambeir A-M, Loiseau AM, Kuntz DA, Vellieux FM, Michels PA, Opperdoes FR (1991) The cytosolic and glycosomal glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma brucei. Kinetic properties and comparison with homologous enzymes. Eur J Biochem 198:429–435

    Article  PubMed  CAS  Google Scholar 

  21. Warkentin DL, Fondy TP (1973) Isolation and characterization of cytoplasmic L-glycerol-3-phosphate dehydrogenase from rabbit-renal-adipose tissue and its comparison with the skeletal-muscle enzyme. Eur J Biochem 36:97–109

    Article  PubMed  CAS  Google Scholar 

  22. Bornstein P, Balian G (1977) Cleavage at Asn-Gly bonds with hydroxylamine. Methods Enzymol 47:132–145

    Article  PubMed  CAS  Google Scholar 

  23. Yang J, Gibson B, Snider J, Jenkins CM, Han X, Gross RW (2005) Submicromolar concentrations of palmitoyl-CoA specifically thioesterify cysteine 244 in glyceraldehyde-3-phosphate dehydrogenase inhibiting enzyme activity: a novel mechanism potentially underlying fatty acid induced insulin resistance. Biochemistry 44:11903–11912

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Toshiaki Imoto of Tottori University for helpful comments and discussion.

Author information

Authors and Affiliations

  1. Graduate School of Agriculture, Kyoto Prefectural University, Sakyo-ku, Kyoto, 606-8522, Japan

    Sumio Ishijima, Tomoyuki Takashima, Tomo Ikemura & Yusuke Izutani

Authors
  1. Sumio Ishijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomoyuki Takashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomo Ikemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yusuke Izutani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sumio Ishijima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishijima, S., Takashima, T., Ikemura, T. et al. Gymnemic acid interacts with mammalian glycerol-3-phosphate dehydrogenase. Mol Cell Biochem 310, 203–208 (2008). https://doi.org/10.1007/s11010-007-9681-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9681-5

Keywords

Search

Navigation