Uroporphyrinogen III bears 8 carboxylic acid groups. Upon conversion into cobalamin, all 8 groups are modified:

• Six of them are amidated by the action of two enzymes
• One is subject to decarboxylation
• One serves as the site of addition of 1-Amino-2-Propanol

Hydrolysis of cobalamin yields the compound cobinamide, which bears the 1-amino-2-propanol moeity. Since cobinamide can feed many mutants defective in cobalamin biosynthesis, it has long been thought that cobinamide serves as an intermediate in cobalamin biosynthesis. The enzymatic activity of a cobinamide kinase (Pseudomonas CobV enzyme, Salmonella CobU enzyme) reinforced this idea. In Salmonella, mutations in the cobD gene are fed aminopropanol. Two pathways have been discussed historically in the literature for the synthesis of 1-amino-2-propanol:

• Decarboxylation of threonine. The failure to detect Threonine Decarboxylase activity has cast a shadow on this pathway.
• Oxidation of threonine to amino-keto-butyrate, spontaneous decarboxylation to amino acetone, and the reduction of this compound to yield aminopropanol

As it turns out, neither of these pathways is likely to be true. Rather, it appears that Threonine-phosphate is decarboxylated to yield 1-Amino-2-propanol phosphate (Brushaber, O"Toole, and Escalante-Semerena. J Biol Chem 273:2684-2691). This compound is likely incorporated to form cobinamide-phosphate directly. The kinase activity of the Cobinamide-phosphate:GTP guanylyltransferase is likely used to incorporate exogenous sources of cobinamide.

Step	Chemical Strcuture	Reactions	Pseudomonas Enzyme	Salmonella Enzyme
1		Kinasing	??	??
2		Decarboxylation	CobC	CobD
3

Last Updated 14 August 2006, by JG Lawrence