The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose

@article{Frey1996TheLP,
  title={The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose},
  author={Perry Allen Frey},
  journal={The FASEB Journal},
  year={1996},
  volume={10},
  pages={461 - 470}
}
  • P. Frey
  • Published 1 March 1996
  • Biology, Chemistry
  • The FASEB Journal
ABSTRACT: The biological interconversion of galactose and glucose takes place only by way of the Leloir pathway and requires the three enzymes galactoki‐ nase, galactose‐1‐P uridylyltransferase, and UDP‐ galactose 4‐epimerase. The only biological importance of these enzymes appears to be to provide for the interconversion of galactosyl and glucosyl groups. Galactose mutarotase also participates by producing the galactokinase substrate α‐D‐galactose from its β‐anomer. The galacto/gluco… 

Structure and Function of Enzymes of the Leloir Pathway for Galactose Metabolism*

Recent advances in the understanding of the structure and function of the Leloir pathway are presented, highlighting their important metabolic role in normal galactose metabolism.

Sugar recognition by human galactokinase

The sugar specificity of the enzyme and the kinetic consequences of mutating residues in the sugar-binding site are investigated in order to improve the understanding of substrate recognition by this enzyme.

Identification of a mutarotase gene involved in D‐galactose utilization in Aspergillus nidulans

It is concluded that GalmB is the physiologically relevant mutarotase for the utilization of D‐galactose in A. nidulans.

UDP‐galactose 4‐epimerase from Kluyveromyces  fragilis – catalytic sites of the homodimeric enzyme are functional and regulated

Dissimilar kinetic patterns of the reconstituted enzyme after treatment with p‐chloromercuribenzoate indicated stability of the dimeric enzyme against fast association–dissociation, which could otherwise generate multiple forms of the enzyme with functional heterogeneity.

Structural basis for the reaction mechanism of UDP-glucose pyrophosphorylase

Isothermal titration calorimetry analyses demonstrated that Mg2+ ion plays a key role in the enzymatic activity of UGPase by enhancing the binding of U GPase to UTP or UDP-glucose, suggesting that this reaction is catalyzed by an ordered sequential Bi Bi mechanism.
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References

SHOWING 1-10 OF 53 REFERENCES

The molecular structure of UDP‐galactose 4‐epimerase from Escherichia coli determined at 2.5 Å resolution

The molecular structure of UDP‐galactose 4‐epimerase from Escherichia coli has now been solved to a nominal resolution of 2.5 Å.

Remodeling hexose-1-phosphate uridylyltransferase: mechanism-inspired mutation into a new enzyme, UDP-hexose synthase.

The mutant H166G catalyzes this reaction, as well as the reverse reaction, by a sequential kinetic mechanism involving ternary complexes as intermediates, and the substrate Km values for the mutant enzyme are similar to those for hexose-1-P uridylyltransferase.

Identification of lysine 153 as a functionally important residue in UDP-galactose 4-epimerase from Escherichia coli.

It is concluded that lysine 153 plays an important role in increasing the chemical reactivity of enzyme-bound NAD+ in the uridine nucleotide-dependent conformational change associated with reductive inactivation and the catalytic activity of UDP-galactose 4-epimerase.

Galactose-1-phosphate uridylyltransferase: isolation and properties of a uridylyl-enzyme intermediate.

It is concluded that the uridylyl-enzyme contains at least one essential sulfhydryl group which is not located in the active site in such a way as to be shielded by substrates.

The importance of binding energy in catalysis of hydride transfer by UDP-galactose 4-epimerase: a 13C and 15N NMR and kinetic study.

The distortion of NAD+ by the binding of UDP is a long-range effect that is transmitted from the substrate binding site to the coenzyme through the protein conformational change, which apparently distorts the pi-electron distribution in the nicotinamide ring and reduces the activation energy for its reduction.

Galactose-1-phosphate uridylyltransferase. Purification of the enzyme and stereochemical course of each step of the double-displacement mechanism.

Results support the authenticity of the isolated uridylyl-enzyme as the true reaction intermediate and show that reaction of the enzyme with (RP)-[2- 14C]UDP alpha S-glucose produces a [2-14C]uridyly l alpha S -enzyme that can be converted by base-catalyzed cyclization to (RP-[ 2-14 C]cUMPS.

The pathway of the adaptive fermentation of galactose by yeast.

Certain yeasts can ferment galactose by the formation of an adaptive 'galactozymase' when placed in aqueous solutions of galactose and in the apparent absence of cell division (Stephenson & Yudkin,
...