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. 1974 Jan;9(1):8–14. doi: 10.1128/iai.9.1.8-14.1974

Isolation and Biochemical Activities of Trehalose-6-Monomycolate of Mycobacterium tuberculosis

Masahiko Kato a,1, Jiro Maeda a
PMCID: PMC414756  PMID: 4271721

Abstract

A monoester of trehalose linked at the 6-position with mycolic acids (trehalose-6-monomycolate) was isolated from the wax D fraction of virulent human Mycobacterium tuberculosis, and its biochemical action on host-cell mitochondria was studied. Trehalose-6-monomycolate showed a delayed toxicity for mice. The 50% lethal dose at 2 weeks was 452 μg. It induced in vitro a swelling of mouse liver mitochondria and uncoupled respiration and phosphorylation in the nicotinamide adenine dinucleotide pathway of the electron transport chain. The site of functional damage was located specifically at coupling site II. Mitochondrial adenosine triphosphatase was slightly stimulated by trehalose-6-monomycolate. These findings indicate that trehalose-6-monomycolate affects mitochondrial oxidative phosphorylation in a similar manner to, but to a lesser extent than, trehalose-6, 6′-dimycolate (cord factor) of M. tuberculosis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRADLEY L. B., JACOB M., JACOBS E. E., SANADI D. R. Uncoupling of oxidative phosphorylation by cadmium ion. J Biol Chem. 1956 Nov;223(1):147–156. [PubMed] [Google Scholar]
  2. Goren M. B. Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv. I. Purification and properties. Biochim Biophys Acta. 1970 Jun 9;210(1):116–126. doi: 10.1016/0005-2760(70)90067-6. [DOI] [PubMed] [Google Scholar]
  3. Goren M. B. Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv. II. Structural studies. Biochim Biophys Acta. 1970 Jun 9;210(1):127–138. doi: 10.1016/0005-2760(70)90068-8. [DOI] [PubMed] [Google Scholar]
  4. Kato M., Asselineau J. Chemical structure and biochemical activity of cord factor analogs. 6,6'-Dimycoloyl sucrose and methyl 6-mycoloyl- -D-glucoside. Eur J Biochem. 1971 Oct 14;22(3):364–370. doi: 10.1111/j.1432-1033.1971.tb01553.x. [DOI] [PubMed] [Google Scholar]
  5. Kato M. Site II-specific inhibition of mitochondria oxidative phosphorylation by trehalose-6,6'-dimycolate (cord factor) of Mycobacterium tuberculosis. Arch Biochem Biophys. 1970 Oct;140(2):379–390. doi: 10.1016/0003-9861(70)90079-2. [DOI] [PubMed] [Google Scholar]
  6. Kato M. Site of action of lipid A on mitochondria. J Bacteriol. 1972 Oct;112(1):268–275. doi: 10.1128/jb.112.1.268-275.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kato M. Studies of a biochemical lesion in experimental tuberculosis in mice. XI. Mitochondrial swelling induced by cord factor in vitro. Am Rev Respir Dis. 1969 Jul;100(1):47–53. doi: 10.1164/arrd.1969.100.1.47. [DOI] [PubMed] [Google Scholar]
  8. Kato M., Tanaka A. Studies of a biochemical lesion in experimental tuberculosis in mice. V. Further study on a toxic lipid fraction in firmly bound lipids. Am Rev Respir Dis. 1967 Sep;96(3):460–468. doi: 10.1164/arrd.1967.96.3.460. [DOI] [PubMed] [Google Scholar]
  9. LARDY H. A., WELLMAN H. Oxidative phosphorylations; rôle of inorganic phosphate and acceptor systems in control of metabolic rates. J Biol Chem. 1952 Mar;195(1):215–224. [PubMed] [Google Scholar]
  10. Maeda J. [Isolation and characterization of toxic glycolipids from the firmly bound lipids of human tubercle bacilli]. Nihon Saikingaku Zasshi. 1972 May;27(3):469–475. doi: 10.3412/jsb.27.469. [DOI] [PubMed] [Google Scholar]
  11. NOLL H., BLOCH H. A toxic lipid component of the tubercle bacillus (cord factor). II. Occurrence in chloroform extracts of young and older bacterial cultures. Am Rev Tuberc. 1953 Jun;67(6):828–852. doi: 10.1164/art.1953.67.6.828. [DOI] [PubMed] [Google Scholar]
  12. NOLL H., BLOCH H. Studies on the chemistry of the cord factor of Mycobacterium tuberculosis. J Biol Chem. 1955 May;214(1):251–265. [PubMed] [Google Scholar]
  13. NOLL H. The chemistry of cord factor, a toxic glycolipid of M. tuberculosis. Bibl Tuberc. 1956;(10):149–183. [PubMed] [Google Scholar]
  14. NOLL H. The chemistry of some native constituents of the purified wax of Mycobacterium tuberculosis. J Biol Chem. 1957 Jan;224(1):149–164. [PubMed] [Google Scholar]
  15. ROE J. H. The determination of sugar in blood and spinal fluid with anthrone reagent. J Biol Chem. 1955 Jan;212(1):335–343. [PubMed] [Google Scholar]
  16. TREVELYAN W. E., HARRISON J. S. Studies on yeast metabolism. I. Fractionation and microdetermination of cell carbohydrates. Biochem J. 1952 Jan;50(3):298–303. doi: 10.1042/bj0500298. [DOI] [PMC free article] [PubMed] [Google Scholar]

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