Methionine proton production

This enzyme s role in humans is to assist the detoxification of propionate derived from the degradation of the amino acids methionine, threonine, valine, and isoleucine. Propionyl-CoA is carboxylated to (5 )-methylmalonyl-CoA, which is epimerized to the (i )-isomer. Coenzyme Bi2-dependent methylmalonyl-CoA mutase isomerizes the latter to succinyl-CoA (Fig. 2), which enters the Krebs cycle. Methylmalonyl-CoA mutase was the first coenzyme B -dependent enzyme to be characterized crystallographically (by Philip Evans and Peter Leadlay). A mechanism for the catalytic reaction based on ab initio molecular orbital calculations invoked a partial protonation of the oxygen atom of the substrate thioester carbonyl group that facilitated formation of an oxycyclopropyl intermediate, which connects the substrate-derived and product-related radicals (14). The partial protonation was supposed to be provided by the hydrogen bonding of this carbonyl to His 244, which was inferred from the crystal structure of the protein. The ability of the substrate and product radicals to interconvert even in the absence of the enzyme was demonstrated by model studies (15). 

Figure 4-4. Intestinal absorption of dietary folates (THF-[Gluy and foUc acid (F) from fortified cereal products and vitamin supplements. In the duodenum and upper jejunum, extra glutamate residues are cleaved by conjugases (y-glutamyl carboxypeptidases). Folate (F) and reduced folate (THF) are absorbed by a proton-coupled, high affinity folate transporter into the mucosal cell, converted to N -methyl THF and exported into the portal circulation. N -methyl THF is taken up into cells by facilitative diffusion, converted to THF by the Bj -requiring methionine synthase and then converted to a polyglutamate.

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