Galactose epimerization

Upon kinetic analysis UDP-galactose is a competitive inhibitor for TDP-galactose epimerization. 

Synthesis of aldohexoses from 422 (n = 2) telomers was achieved by way of cyanide intermediate s. On treatment with potassium cyanide, each of the dichloromethyl compounds 449 and 451 gave28 5 a pair of epimeric nitriles (463-466) that were converted, in moderate yield, into DL-galactose, DL-altrose, DL-idose, and DL-glucose by conventional procedures involving esterification, reduction, and final hydrolysis of the dichloromethyl group. 

Unsaturated sugars, namely glycals, such as 3,4,6-tri-Oacetyl-l, 5-anhydro-2-dcoxy-D-r//v/-/w7o-hex-1-enetol and the d-/v.yo epimer react with xenon difluoride in the presence of a boron trifluoride-diethyl ether complex to give a mixture of C2 epimeric fluorides.45,46 Tri-O-acctyl-D-galactal treated with xenon difluoride in trichlorofluoromcthane below 5 C forms after hydrolysis (0.5 M HC1) 2-deoxy-2-fluoro-D-galactose in 63% overall yield.47... 

The galactose 1-phosphate is then converted to its epimer at C-4, glucose 1-phosphate, by a set of reactions in which uridine diphosphate (UDP) functions as a coenzyme-like carrier of hexose groups (Fig. 14-11). The epimerization involves first the oxidation of the C-4 —OH group to a ketone, then reduction of the ketone to an —OH, with inversion of the configuration at C-4. NAD is the cofactor for both the oxidation and the reduction. 

L-talaric acid, which could also arise from L-talose or L-altrose. It was possible to eliminate the latter alternative, because talose was known to be the epimer of galactose, l-Talose thus has formula (22), and its enantio-morph is epimeric with D-galactose. Therefore, D-galactose has formula (14). 

It has been postulated (37) that lactulose is formed from lactose by the Lobry de Bruyn and Alberda van Ekenstein transformation, whereby glucose is isomerized to fructose via an enol intermediate. In turn, two mechanisms have been proposed for the degradation of this intermediate (38)- One involves the addition of a proton to the enediol resulting in epimeric aldoses and the original ketose, while the other involves 8-elimination to yield galactose and saccharinic acids. The authors experimental data would tend to better support the second pathway. 

A model reaction in which UDP-D-glucose 4-epimerase was shown20,1698 to form an inactive NADH-enzyme complex on incubation with either D-glucose or D-galactose and UMP has been shown1690 to be unrelated to the epimerization reaction. The label from D-galactose-J-t was transferred to NAD, and D-galactonic acid was isolated. Oxidation therefore occurred at C-l, which is normally involved in combination with UDP. 

Oxidation of the C4 hydroxyl group by NAD+ forms a ketone plus NADH, and reduction of the ketone by NADH yields UDP-galactose. The result is an epimerization at carbon 4 of the pyranose ring. 

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