UDP galactose

UDP-Glucose Galactose 1-phosphate -p UTP Galactose 1-phosphate -P UDP-glucose 

Three different enzymes may catalyze the formation of UDP-galactose (1) UDP-glucose 4-epimerase (UDP-galactose 4-epimerase) (2) UDP-galactose pyrophosphorylase and (3) galactose 1-phosphate uridyl 

Since the aspects of galactose metabolism which have been touched upon briefly above are covered in many reviews (see above), the following discussion will be concaned mainly with some recent work on the mechanism of the UDP-glucose 4-epimerase reaction. 

In the early studies of this reaction it was observed that the enzyme from calf liver requires the addition of a catalytic amount of DPN for activity, whereas DPNH causes inhibition (Maxwell, 1956). In contrast, the purified yeast enzyme does not need exogenous DPN, nor is it inhibited by DPNH. It is now clear that the enzymes of plant and animal tissues need exogenous DPN, whereas in microorganisms (e.g., yeast and . coli) DPN is tightly bound. 

Evidence for cleavage of the C4 — H bond of the hexose moiety in the course of epimerization was obtained in studies of the reaction rates of UDP-glucose 4[ H] and UDP-galactose [ H], These tritiated substrates showed a positive isotope effect with a relative reaction rate of about 0.5 as compared to the normal species, when tested with either the E. coli or the yeast epimerase (Nelsestuen and Kirkwood, 1970a). These results were in contrast to those obtained in a previous experiment in which the tritiated species reacted considerably faster than the normal nucleotide sugars (Bevill et al., 1965). 

In a system where UDP-Gal regeneration is the goal, the inclusion of a one-step conversion of UTP to UDP-Gal using the enzyme UDP-Gal pyrophosphorylase would be ideal. Unfortunately, this enzyme is not commercially available, nor is it easy to prepare from biological sources [8]. Luckily, an alternative biosynthetic pathway to UDP-Gal exists. In nature, UDP-Glc is a central intermediate for the biosynthesis of UDP-Gal and UDP-GlcUA, as well as other sugar nucleotides. The enzyme UDP-Glc pyrophosphorylase (UDPGP EC 2.1.1.9) required for the conversion of UTP to UDP-Glc can be purchased. The UDP-Gal 4-epimerase 

Other groups have used routes based on this initial concept for the synthesis of oligosaccharides [10]. A similar recycling system was reported by Auge et al. for 

The UDP-Gal epimerase system was also one of the early methods to employ pyruvate kinase (PK EC 2.7.1.40) for the conversion of UDP to UTP, with the simultaneous formation of pyruvate from phospho(enol)pyruvate (PEP). Previous kinase systems employed were either more expensive (nucleoside diphosphate kin-ase(EC 2.7.4.6)/ATP) or were thermodynamically less favorable (acetate kinase(EC 2.7.2.1)/acetyl phosphate). Another potentially usefid kinase system has recently been described. Noguchi and Shiba have utilized polyphosphate kinase (PPK) for the formation of UTP from UDP in a UDP-Gal recycling system [13]. Previously, PPK was shown to catalyze the reversible transfer of phosphate from ATP to ADP. Recently, it has been discovered that PPK will also accept other NDP and NTP substrates. For application to recycling systems, poly(phosphate) is more affordable than PEP as a phosphoryl donor. Synthetically, replacement of PK with PPK in the UDPGE-based recycling system efficiently provided LacNAc from GlcNAc on a multi-gram scale. 

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Galactose, a constituent of the disaccharide lactose found in dairy products, is metabolized by a patiiwav that includes the isomerization of UDP-galactose to UDP-glucose. where UDP = uridylyl diphosphate. The enzyme responsible for the transformation uses NAD+ as cofactor. Propose a mechanism. 

P2Y14 Placenta, adipose tissue, stomach, intestine, discrete brain regions UDP glucose = UDP-galactose Gq/Gu... 

Stable and potent P2Y2 receptor agonists are being administered by inhalation as a potential treatment for cystic fibrosis. P2YH receptors are unusual in that they are activated by UDP-glucose, UDP galactose and UDP-N-acetylglucosamine [22],... 

The first, definitive identification of KDO as a constituent of the LPS from Escherichia colt 0111-B4 (and from its UDP-galactose-4-epi-merase-less mutant, J-5) was reported by Heath and Ghalambor.29 When analyzing their LPS preparations for 3,6-dideoxy-L-xyZo-hex-... 

Sprang, H., Kruithof, B., Leijendekker, R., Slot, J. W., van Meer, G., and van der Sluijs, P., 1998, UDP-galactose ceramide galactosyltransferase is a class 1 integral membrane protein of the endoplasmic reticulum. J Biot Chem 273 25880-25888. 

Nobel and Wang reported that the permeability of the outer membranes of chloroplasts was increased by exposure to ozone (at 30 ppm for 5 min). They hypothesized that the effect was lipid oxidation. Freebaim showed that ozone inhibited respiratory activities of isolated mitochondria, and Lee found that the effect of ozone on oxidative phosphorylation was greater than on oxygen uptake. Mudd et reported that the metabolism of UDP-galactose by isolated... 

This enzyme [EC 2.4.1.46], also referred to as UDP-galactose 1,2-diacylglycerol 3 -/3-galactosyltransferase,... 

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