ABSTRACT
I. Introduction .....................................................................................................381 II. Metabolic Associations ................................................................................. 382
A. Methionine Synthase and Methionine Synthase Reductase .................... 382 B. 5,10-Methylenetetrahydrofolate Reductase ..............................................384 C. Biochemical Utilization of 5-Methyl-THF ................................................386 D. Remethylation of Hcy .............................................................................. 386 E. Utilization of Folic Acid .......................................................................... 388
III. Potential Links to Disease Risk .................................................................... 389 A. Folate-Vitamin B12-Related Metabolites in Severe B12 De ciency .......389 B. Folate-Vitamin B12-Related Metabolites in “Subclinical” or Moderate B12 De ciency .........................................................................390 C. Effects of Concomitant Low Vitamin B12 and High Folate Status .........390 D. Pregnancy Complications ........................................................................ 393 E. Folate-Vitamin B12 Interactions and Osteoporosis ................................ 394
IV. Summary .........................................................................................................394 Acknowledgments ......................................................................................... 395 References ..................................................................................................... 395
The link between folate and vitamin B12 (cobalamin) metabolism has been known for decades. Early studies of the biochemistry of the sulfur-containing amino acids (cysteine, homocysteine [Hcy], and methionine) led to the discovery that transmethylation pathways exist in both rats and humans [1,2], that “biologically labile methyl groups” can be synthesized, and that the dietary requirement for methionine can be met by feeding Hcy plus folate and vitamin B12 [3,4]. The discovery, puri cation, and early kinetic studies of cobalamin-dependent methionine synthase (MS) were later accomplished by work from a number of laboratories, thus clarifying the metabolic connection between folate and vitamin B12 [5,6]. This chapter summarizes the research in the past decade that has led to our current understanding of the reaction synthesized by this unique enzyme.
