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MetaCyc Enzyme: trehalose-6-phosphate synthase

Gene: TPS1 Accession Number: G-454 (MetaCyc)

Synonyms: GGS1, CIF1, BYP1, FDP1, GLC6, TSS1, α,α-trehalose-phosphate synthase [UDP-forming] 56 kDa subunit, general glucose sensor subunit 1, glycogen metabolism control protein GLC6, trehalose synthase complex catalytic subunit TPS1

Species: Saccharomyces cerevisiae

Component of: trehalose synthase complex (extended summary available)

Summary:
The apparent molecular mass of the polypeptide was determined by SDS-PAGE [Chaudhuri08].

TPS1 is part of the trehalose synthase protein complex (see trehalose synthase complex). Isolation of the TPS1 polypeptide from the complex showed that it can also function independently as a trehalose-6-phosphate synthase [Chaudhuri08, Chaudhuri09].

The native, uncomplexed TPS1 was purified and shown to be active as a trehalose-6-phosphate synthase, although it was unstable when separated from the complex. It appeared to be regulated by association and dissociation with other protein components [Chaudhuri08]. Its substrate specificity and factors for optimal activity have been determined [Chaudhuri09].

A purified, recombinant GST-TPS1 fusion protein expressed in Escherichia coli also showed high trehalose-6-phosphate synthase activity, and a H223Y mutant showed increased trehalose-6-phosphate synthase activity as compared with wild-type [De01].

TPS1 was shown to be required for α,α-trehalose synthesis and for growth on D-glucose and D-fructose. Mutant studies suggested that a portion of TPS1 may occur in uncomplexed form in vivo [Bell98]]|. TPS1 activity was inhibited by phosphate when TPS1 was in the trehalose synthase complex, but phosphate stimulated the monomeric form of TPS1 [Bell98].

Gene Citations: [Vuorio93]

Molecular Weight of Polypeptide: 56.148 kD (from nucleotide sequence), 59.0 kD (experimental) [Chaudhuri08 ]

Unification Links: ArrayExpress:Q00764 , DIP:DIP-744N , Entrez-gene:852423 , Mint:MINT-618278 , ModBase:Q00764 , Pride:Q00764 , Protein Model Portal:Q00764 , SMR:Q00764 , String:4932.YBR126C , Swiss-Model:Q00764 , UniProt:Q00764

Relationship Links: CAZy:IN-FAMILY:GT20 , InterPro:IN-FAMILY:IPR001830 , InterPro:IN-FAMILY:IPR012766 , Pfam:IN-FAMILY:PF00982

Gene-Reaction Schematic: ?

Credits:
Revised 07-Feb-2012 by Fulcher CA , SRI International


Enzymatic reaction of: trehalose-6-phosphate synthase

Synonyms: UDP-glucose-glucosephosphate glucosyltransferase

EC Number: 2.4.1.15

UDP-α-D-glucose + α-D-glucose 6-phosphate <=> UDP + α,α-trehalose 6-phosphate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for α-D-glucose 6-phosphate: α-D-mannose 6-phosphate [Chaudhuri09 ] , β-D-fructofuranose 6-phosphate [Chaudhuri09 ]

In Pathways: chitin biosynthesis , trehalose biosynthesis I

Summary:
TPS1 activity was inhibited by phosphate when TPS1 was in the trehalose synthase complex, but phosphate stimulated the monomeric form of TPS1 [Bell98].

Enzyme activity was stimulated by the polyanions heparin and chondroitin sulfate. GDP-α-D-glucose or dTDP-α-D-glucose could substitute for UDP-α-D-glucose as D-glucose donor but were less effective, and ADP-α-D-glucose showed very little activity. Maximum activity was see with α-D-glucose 6-phosphate as glucosyl acceptor. followed by α-D-mannose 6-phosphate and β-D-fructofuranose 6-phosphate, while D-glucosamine 6-phosphate was not effective as a glucosyl an acceptor [Chaudhuri09].

Metal cofactors were not essential for activity, but Mn2+ and Zn2+ stimulated activity. Less stimulation was found with Cu2+, Fe2+ and Co2+. However, Pb2+, Ag+, Ba2+, Ca2+, Mg2+ and Cd2+ reduced activity to below control levels. Thiol modification reagents and metal chelators showed little reduction in activity and some were slightly stimulatory depending on concentration [Chaudhuri09].

An intrinsic isomerase activity was also observed that converted β-D-fructofuranose 6-phosphate to D-glucopyranose 6-phosphate, and α-D-mannose 6-phosphate to D-glucopyranose 6-phosphate [Chaudhuri09].

Activators (Unknown Mechanism): Mn2+ [Chaudhuri09] , Zn2+ [Chaudhuri09] , β-D-fructofuranose 6-phosphate [Londesborough93]

Inhibitors (Unknown Mechanism): phosphate [Londesborough93]

Primary Physiological Regulators of Enzyme Activity: phosphate

Kinetic Parameters:

Substrate
Km (μM)
Citations
UDP-α-D-glucose
2000.0
[Chaudhuri09]
α-D-glucose 6-phosphate
4500.0
[Chaudhuri09]

T(opt): 40 °C [Chaudhuri09]

pH(opt): 8.5 [Chaudhuri09]


Subunit of: trehalose synthase complex

Species: Saccharomyces cerevisiae

Subunit composition of trehalose synthase complex = [TPS3][TSL1][TPS2][TPS1]
         trehalose synthase complex regulatory subunit TPS3 = TPS3 (summary available)
         trehalose synthase complex regulatory subunit TSL1 = TSL1 (summary available)
         trehalose-6-phosphate phosphatase = TPS2 (summary available)
         trehalose-6-phosphate synthase = TPS1 (extended summary available)

Summary:
In Saccharomyces cerevisiae, α,α-trehalose and glycogen are major storage carbohydrates. α,α-trehalose is also involved in resistance to heat, dessication, and osmolarity changes. Changes in α,α-trehalose biosynthesis affect growth, glycogen accumulation and sporulation (in [De01]).

In early work on α,α-trehalose biosynthesis in Saccharomyces cerevisiae, trehalose-6-phosphate synthase was shown to transfer the D-glucose residue from UDP-α-D-glucose to α-D-glucose 6-phosphate, producing α,α-trehalose 6-phosphate and UDP. Dephosphorylation of α,α-trehalose 6-phosphate by trehalose-6-phosphate phosphatase produced α,α-trehalose [CABIB58]. Subsequent work identified a high molecular weight protein complex in Saccharomyces cerevisiae known as the trehalose synthase complex which contained both trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase activities [CABIB58, Londesborough91, Vandercammen89, Londesborough93].

Currently, characterization of the exact subunit composition and subunit stoichiometry in the trehalose synthase complex remains incomplete. The trehalose-6-phosphate synthase product of gene TPS1 (TSS1), the trehalose-6-phosphate phosphatase product of gene TPS2, and two regulatory protein products of genes TSL1 and TPS3 are known to be components of the 630-800 kDa trehalose synthase protein complex. The presence of all components is necessary for optimal activity [Londesborough91, Vandercammen89, Bell98], although both TPS1 and TPS2 are also functional as monomers. The reason for the existence of the complex, and its role in metabolism, remain incompletely defined [Chaudhuri08].

Credits:
Created 06-Feb-2012 by Fulcher CA , SRI International


Enzymatic reaction of: trehalose-6-phosphate phosphatase (trehalose synthase complex)

EC Number: 3.1.3.12

α,α-trehalose 6-phosphate + H2O <=> α,α-trehalose + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: chitin biosynthesis , trehalose biosynthesis I


Enzymatic reaction of: trehalose-6-phosphate synthase (trehalose synthase complex)

EC Number: 2.4.1.15

UDP-α-D-glucose + α-D-glucose 6-phosphate <=> UDP + α,α-trehalose 6-phosphate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: chitin biosynthesis , trehalose biosynthesis I


References

Bell98: Bell W, Sun W, Hohmann S, Wera S, Reinders A, De Virgilio C, Wiemken A, Thevelein JM (1998). "Composition and functional analysis of the Saccharomyces cerevisiae trehalose synthase complex." J Biol Chem 273(50);33311-9. PMID: 9837904

CABIB58: CABIB E, LELOIR LF (1958). "The biosynthesis of trehalose phosphate." J Biol Chem 231(1);259-75. PMID: 13538966

Casu89: Casu, B. (1989). "in Heparin: Chemical and Biological Properties, Clinical Applications." Lane, D. A., and Lindahl, U., Eds, pp 25-49, CRC Press, Boca Raton, FL.

Chaudhuri08: Chaudhuri P, Basu A, Ghosh AK (2008). "Aggregation dependent enhancement of trehalose-6-phosphate synthase activity in Saccharomyces cerevisiae." Biochim Biophys Acta 1780(2);289-97. PMID: 18166160

Chaudhuri09: Chaudhuri P, Basu A, Sengupta S, Lahiri S, Dutta T, Ghosh AK (2009). "Studies on substrate specificity and activity regulating factors of trehalose-6-phosphate synthase of Saccharomyces cerevisiae." Biochim Biophys Acta 1790(5);368-74. PMID: 19289151

De01: De Silva-Udawatta MN, Cannon JF (2001). "Roles of trehalose phosphate synthase in yeast glycogen metabolism and sporulation." Mol Microbiol 40(6);1345-56. PMID: 11442833

Gatti79: Gatti, G., Casu, B., Hamer, G. K., Pelin, A. S. (1979). Macromolecules 12:1001-1007.

Londesborough91: Londesborough J, Vuorio O (1991). "Trehalose-6-phosphate synthase/phosphatase complex from bakers' yeast: purification of a proteolytically activated form." J Gen Microbiol 1991;137 ( Pt 2);323-30. PMID: 1849964

Londesborough93: Londesborough J, Vuorio OE (1993). "Purification of trehalose synthase from baker's yeast. Its temperature-dependent activation by fructose 6-phosphate and inhibition by phosphate." Eur J Biochem 1993;216(3);841-8. PMID: 8404904

Vandercammen89: Vandercammen A, Francois J, Hers HG (1989). "Characterization of trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase of Saccharomyces cerevisiae." Eur J Biochem 182(3);613-20. PMID: 2546763

Vuorio93: Vuorio OE, Kalkkinen N, Londesborough J (1993). "Cloning of two related genes encoding the 56-kDa and 123-kDa subunits of trehalose synthase from the yeast Saccharomyces cerevisiae." Eur J Biochem 1993;216(3);849-61. PMID: 8404905


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, biocyc12.