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Gene Review

Gmds  -  GDP-mannose 4, 6-dehydratase

Mus musculus

Synonyms: BC031788, C87208, GDP-D-mannose dehydratase, GDP-mannose 4,6 dehydratase, GMD
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Disease relevance of Gmds

  • Intermittent injections of GMDP to Mycobacterium tuberculosis-infected mice reduced the viable bacilli in the lungs, but increased the counts in the spleens at 16 weeks, but not at earlier harvests after infection [1].
  • We used monoclonal antibody, generated against N-acetylglucosaminyl-beta1-4-N-acetylmuramyl-alanyl-d-isoglutamine (GMDP), and phage display libraries of random peptides to select for oligopeptides, that mimic GMDP in their biological activity [2].
  • Meth A fibrosarcoma cells (5 x 10(5) were inoculated intradermally into BALB/c mice on day 0, and compound A-103 and/or GMDP was administered intravenously (i.v.) on days 7 and 9 [3].
  • There was no change in the duration or depth of neutropenia in mice treated with GMDP for 3 consecutive days (2.5 or 25 mg kg-1) starting the day after CY injection [4].

High impact information on Gmds

  • In vitro experiments with extracts of PLR1.3 cells confirmed the failure to convert GDP-mannose to GDP-fucose and indicated that the defect is in GDP-mannose 4,6-dehydratase (EC, the first enzyme in the conversion of GDP-mannose to GDP-fucose [5].
  • By using radioligand analysis, murine peritoneal macrophages were shown to express several hundred high-affinity cell surface GMDP-binding sites (Ka 350 pM) [6].
  • Hybridomas producing monoclonal anti-idiotypic antibodies (anti-id MAbs) to N-acetylglucosaminyl-beta 1-4-N-acetylmuramyl-alanyl-D-isoglutamine (GMDP) were developed [7].
  • Strikingly, the amount of nitrotyrosine measured after LAM plus IFN-gamma, or LAM plus the low molecular weight adjuvant glutamylmuramyl dipeptide (GMDP), increased significantly in the presence of L-NMMA [8].
  • The inhibitory activity of GMDP became even more pronounced when testing macrophages from Mycobacterium bovis BCG-infected mice [1].

Chemical compound and disease context of Gmds


Biological context of Gmds

  • Synergism of GMDP and tuftsin was found in phagocytosis stimulation assay [9].

Anatomical context of Gmds

  • All the GMD compounds except GMD-323 showed potent inducing activities for IL-1 and tumoricidal macrophages, especially GMD-324 and -326, which exhibited much higher activity than GLA-60 [10].
  • Mixing experiments with Lec13 cytosol identified the first enzyme of the conversion pathway (GDP-mannose 4,6-dehydratase, EC as the site of the block [11].
  • However, these results do not explain readily the grounds for the contrasting effects of GMDP on the growth patterns of tubercle bacilli in the lungs and spleens [1].
  • Modulation of Ia expression resulted from direct action of GMDP on macrophages, rather than from effect of cytokines released by T-cells [12].
  • In this study flow cytometry was used to show that macrophages were the major population of murine peritoneal exudate cells (MPEC), increasing Ia expression upon treatment with N-acetylglucosaminyl-beta 1-4-N-acetylmuramyl-alanyl-D-isoglutamine (GMDP) [12].

Associations of Gmds with chemical compounds

  • The constitutively active de novo pathway involves conversion of cellular GDP-D-mannose to GDP-L-fucose by GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (FX) [13].
  • The O2 production by phorbol myristate-induced peritoneal macrophages in vitro was reduced by preinjection of mice with 100 microg of GMDP [1].
  • The modulation of tumour necrosis factor-alpha, interleukin-1 alpha and glucose levels with GMDP and other analogues of muramyl dipeptide [14].
  • With the addition of GMDP, A-103 did not enhance the production of tumor necrosis factor (TNF) on the basis of L929 cell lysis.(ABSTRACT TRUNCATED AT 250 WORDS)[3]
  • In addition, at the doses used, the time of administration of GMDP relative to CY did not alter this response [4].

Analytical, diagnostic and therapeutic context of Gmds

  • Photoaffinity labeling followed by SDS-PAGE enabled us to identify 32-34 and 38 kDa proteins inside these cells that bound GMDP specifically [6].
  • Injections of GMDP selectively ameliorated also in the lungs the spontaneous relapse of infection following chemotherapy [1].


  1. The effect of glucosaminylmuramyl dipeptide injection to mice on the course of tuberculous infection and in vitro superoxide anion production. Venkataprasad, N., Ledger, P., Ivanyi, J. Int. Arch. Allergy Immunol. (1997) [Pubmed]
  2. Identification of pentadecapeptide mimicking muramyl peptide. Laman, A.G., Shepelyakovskaya, A.O., Berezin, I.A., Boziev, K.M., Rodionov, I.L., Chulina, I.A., Malakhova, G.V., Brovko, F.A., Murashev, A.N., Korpela, T.K., Nesmeyanov, V.A. Vaccine (2007) [Pubmed]
  3. Combined effects of synthetic lipid A analogs or bacterial lipopolysaccharide with glucosaminylmuramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice. Shimizu, T., Iwamoto, Y., Yanagihara, Y., Ikeda, K., Achiwa, K. Int. J. Immunopharmacol. (1992) [Pubmed]
  4. Study on the reduction of chemotherapy induced neutropenia in mice using glucosaminylmuramyl dipeptide. Armstrong, N.A., Bolton, E.J., Morris, D.L. Arzneimittel-Forschung. (1999) [Pubmed]
  5. Mouse lymphoma cell lines resistant to pea lectin are defective in fucose metabolism. Reitman, M.L., Trowbridge, I.S., Kornfeld, S. J. Biol. Chem. (1980) [Pubmed]
  6. Biochemical characterization of glucosaminylmuramyldipeptide binding sites of murine macrophages. Golovina, T.N., Sumaroka, M.V., Samokhvalova, L.V., Shebzukhov YuV, n.u.l.l., Andronova, T.M., Nesmeyanov, V.A. FEBS Lett. (1994) [Pubmed]
  7. Production and characterization of monoclonal anti-idiotypic antibodies to muramylpeptide. Mareeva TYu, n.u.l.l., Kotova, O.V., Golovina, T.N., Nesmeyanov, V.A. FEBS Lett. (1994) [Pubmed]
  8. Nitrotyrosine formation after activation of murine macrophages with mycobacteria and mycobacterial lipoarabinomannan. Venkataprasad, N., Riveros-Moreno, V., Sosnowska, D., Moreno, C. Clin. Exp. Immunol. (1999) [Pubmed]
  9. Synthesis and immunological evaluation of the conjugates composed from a muramyl peptide GMDP and tuftsin. Titov, V.M., Meshcheryakova, E.A., Balashova, T.A., Andronova, T.M., Ivanov, V.T. Int. J. Pept. Protein Res. (1995) [Pubmed]
  10. Adjuvant activities of synthetic lipid A subunit analogues and its conjugates with muramyl dipeptide derivatives. Maeda, H., Saiki, I., Ishida, H., Kiso, M., Hasegawa, A., Azuma, I. Vaccine (1989) [Pubmed]
  11. Two Chinese hamster ovary glycosylation mutants affected in the conversion of GDP-mannose to GDP-fucose. Ripka, J., Adamany, A., Stanley, P. Arch. Biochem. Biophys. (1986) [Pubmed]
  12. N-acetylglucosamine-containing muramyl peptides directly affect macrophages. Khaidukov, S.V., Komaleva, R.L., Nesmeyanov, V.A. Int. J. Immunopharmacol. (1995) [Pubmed]
  13. Differential gene expression of GDP-L-fucose-synthesizing enzymes, GDP-fucose transporter and fucosyltransferase VII. Niittymäki, J., Mattila, P., Renkonen, R. APMIS (2006) [Pubmed]
  14. The modulation of tumour necrosis factor-alpha, interleukin-1 alpha and glucose levels with GMDP and other analogues of muramyl dipeptide. Adeleye, T.A., Moreno, C., Ivanyi, J., Aston, R. APMIS (1994) [Pubmed]
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