Disease relevance of trehalose

• A high incidence of tumor regression was observed in guinea pigs bearing transplantable, line-10 hepatocellular carcinomas when synthetic muramyl dipeptides combined with trehalose dimycolate in oil-in-water emulsions were injected directly into the tumors [1].
• Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence [2].
• Using a genetically engineered mutant of Staphylococcus aureus alpha-hemolysin to create pores in the cellular membrane, we were able to load trehalose into cells [3].
• We have now expressed the otsA and otsB genes of Escherichia coli, which encode trehalose biosynthetic enzymes, in human primary fibroblasts using a recombinant adenovirus vector [4].
• Trehalose synthesis is induced upon exposure of Escherichia coli to cold and is essential for viability at low temperatures [5].

Psychiatry related information on trehalose

• Oral administration of trehalose, the most effective of these disaccharides, decreased polyglutamine aggregates in cerebrum and liver, improved motor dysfunction and extended lifespan in a transgenic mouse model of Huntington disease [6].
• Disruption of insulin pathways alters trehalose level and abolishes sexual dimorphism in locomotor activity in Drosophila [7].
• We show here that glycerol, the sugar alcohol erythritol, the disaccharide trehalose and its breakdown product glucose reduce the rate of polymerization of wild-type neuroserpin and the Ser49Pro mutant that causes dementia [8].

High impact information on trehalose

• Recent studies clarified the unusual structures of arabinogalactan as well as of extractable cell wall lipids, such as trehalose-based lipooligosaccharides, phenolic glycolipids, and glycopeptidolipids [9].
• Overexpression of the Tre1 gene restored the taste sensitivity to trehalose in the Tre1 deletion mutant [10].
• Upon return to 30 degrees C, TPS1, TPS2, and HSP104 mRNAs, trehalose levels and tolerance to freezing fall dramatically within minutes [11].
• Multiple effects of trehalose on protein folding in vitro and in vivo [12].
• Transgenic rescue experiments showed that Gr5a confers response to trehalose [13].

Chemical compound and disease context of trehalose

• Trehalose-6-phosphate phosphorylase is part of a novel metabolic pathway for trehalose utilization in Lactococcus lactis [14].
• We have isolated and purified to homogeneity an alpha,alpha'-trehalose 6-monomycolate:alpha,alpha'-trehalose mycolyltransferase (trehalose mycolyltransferase) from Mycobacterium smegmatis that catalyzes the exchange of a mycolyl group between trehalose, trehalose 6-monomycolate (TM), and trehalose 6,6'-dimycolate (TD) [15].
• N-acylkansosamine. A novel N-acylamino sugar from the trehalose-containing lipooligosaccharide antigens of Mycobacterium kansasii [16].
• In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette-Guérin is due principally to trehalose mycolates [17].
• TmMBP is able to bind maltose, maltotriose and trehalose with dissociation constants in the nanomolar to micromolar range, combining the substrate specificities of the homologs from the mesophilic bacterium E. coli and the hyperthermophilic archaeon Thermococcus litoralis [18].

Biological context of trehalose

• These findings reconcile conflicting reports on the role of trehalose in stress tolerance, provide a novel tool for accessing protein folding intermediates, and define new parameters for modulating stress tolerance and protein aggregation [12].
• Trehalose synthase: guard to the gate of glycolysis in yeast [19]?
• Overexpression of RGS2 generates phenotypes consistent with low activity of cAMP-dependent protein kinase A (PKA), such as enhanced accumulation of trehalose and glycogen, enhanced heat resistance and elevated expression of STRE-controlled genes [20].
• Although this accumulation of trehalose did not influence growth at 16 degrees C, it enhanced cell viability when the temperature fell further to 4 degrees C. Before the trehalose build-up, levels of mRNA encoding OtsA/OtsB increased markedly [5].
• A hydrophobic pocket and tunnel extending 21 A into the core of the protein indicates the location of a probable trehalose monomycolate binding site [21].

Anatomical context of trehalose

• Thus the interpretation placed on the finding that trehalose can stabilize dry membranes must be regarded from this perspective as well [22].
• Human primary fibroblasts expressing trehalose could be maintained in the dry state for up to five days [4].
• Low concentrations (0.2 M) of trehalose permitted long-term post-thaw survival of more than 80% of 3T3 fibroblasts and 70% of human keratinocytes [3].
• The discovery informs about the evolution of plant metabolism and how chloroplasts of prokaryotic origin use an intermediate of the ancient trehalose pathway to report the metabolic status of the cytosol [23].
• We demonstrate by heterologous expression in a Drosophila S2 cell line that Gr5a encodes a receptor tuned to trehalose [24].

Associations of trehalose with other chemical compounds

• In two different mutants that carry deletions in Gr5a, electrophysiological and behavioral responses to trehalose were diminished but the response to sucrose was unaffected [13].
• The pH optimum; Michaelis constant; electrophoretic mobility in starch; thermal denaturation at pH 4.0 and 7.0; and inhibition by turanose, alpha-methylglucoside and trehalose were the same in purified enzyme from normal and mutant cells [25].
• Crystal structure of MalK, the ATPase subunit of the trehalose/maltose ABC transporter of the archaeon Thermococcus litoralis [26].
• Many organisms that withstand desiccation express the disaccharide trehalose [4].
• Here we show that isoniazid induced several genes that encode proteins physiologically relevant to the drug's mode of action, including an operonic cluster of five genes encoding type II fatty acid synthase enzymes and fbpC, which encodes trehalose dimycolyl transferase [27].

Gene context of trehalose

• One such mutation was further characterized and the affected gene was shown to be identical to TPS2 which encodes trehalose phosphate phosphatase, an enzyme catalysing the second step in trehalose biosynthesis [28].
• Tpk2 negatively regulates genes involved in iron uptake and positively regulates genes involved in trehalose degradation and water homeostasis [29].
• The neutral trehalase is responsible for intracellular hydrolysis of trehalose, in contrast to the acid trehalase, which is responsible for utilization of extracellular trehalose [30].
• The role of the putative trehalase Nth2p in trehalose metabolism is not known [30].
• Deletion of TPS1 totally abolished TPS activity and measurable trehalose, whereas deletion of any of the other genes in most cases reduced both [31].

Analytical, diagnostic and therapeutic context of trehalose

• Regression of tumors in guinea pigs after treatment with synthetic muramyl dipeptides and trehalose dimycolate [1].
• Of tardigrades, trehalose, and tissue engineering [32].
• Trehalose-based reagents may be important for bedside testing and in developing countries where refrigeration is unreliable [33].
• Trehalose expression confers desiccation tolerance on human cells [4].
• We report that the introduction of low concentrations of intracellular trehalose can greatly improve the survival of mammalian cells during cryopreservation [3].

References