Q17-73E - Organic Chemistry (Mcmurry)

Question

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

Step-by-Step Solution

Answer

Conversion occur in two step:

• Deprotonation and NAD⁺ attack
• NADH attack

Step 1: NAD + as co- factor

If ${\mathbf{NAD}}^{\mathbf{+}}$ is used as a cofactor then it must be oxidizing ${\mathbf{UDP}}^{\mathbf{-}}$ galactose. For this oxidation to occur deprotonation of ${\mathbf{UDP}}^{\mathbf{-}}$ galactose is must

Step 2: UDP-galactose to UDP-glucose conversion mechanism

The mechanism for conversion of UDP-galactose to UDP-glucose involves two steps: 

 

Step 1: For deprotonation base can be used. It will remove hydrogen ion from UDP-galactose making oxygen negatively charged and this oxygen will create double bond with C4 facilitating hydride ion removal by ${\mathrm{NAD}}^{+}$ and creating a ketone group at C4 and also NADH.

 

Step 2: The NADH formed in step 1 can now attack the molecule at C4 and cause conversion of ketone to hydroxyl group again but now in the hydroxyl group is in inverted configuration at C4 giving UDP-glucose.