Interaction of folylpolyglutamates with enzymes in one-carbon metabolism.
Of all the coenzymes, tetrahydrofolate exhibits the most structural diversity. The relationship of these structural forms to physiological function is under intense study by numerous research groups. In textbooks, tetrahydrofolate (tetrahydropteroylmonoglutamate) is shown as the coenzyme of one-carbon metabolism, but it has been known for several decades that the physiologically active forms of the coenzyme contain from 4 to 7 glutamyl residues linked by amide bonds through the gamma-carboxyl group. These glutamyl residues do not serve a direct function in transferring the one-carbon group. The tetrahydrofolylpolyglutamates were originally thought to be simply storage forms of the coenzyme, but studies now show that the polyglutamate chain of the coenzyme affects the transport properties of the coenzyme, alters the kinetic properties of many enzymes in one-carbon metabolism, and results in channeling of the coenzyme between several enzymes. In general, the dissociation constants of this group of enzymes for the tetrahydrofolylpolyglutamates are very low, in the 0.1 to 1 microM range. The concentration of the coenzyme in the cell appears to be similar to the concentration of folate-utilizing enzymes, suggesting that the concentration of unbound coenzyme in the cell may be very low. Several of the enzymes in one-carbon metabolism are either multifunctional proteins or multienzyme complexes. An active area of research is to determine if there is a functional relationship between these multifunctional enzymes and the polyglutamate portion of the coenzyme.
Schirch
V
V
Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond 23298.
Strong
W B
WB
D002244:Carbon / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism; D005492:Folic Acid / Q000031:analogs & derivatives*; D006706:Homeostasis; D007700:Kinetics; D011624:Pteroylpolyglutamic Acids / Q000378:metabolism*
D004798:Enzymes; D011624:Pteroylpolyglutamic Acids; D002244:Carbon; D005492:Folic Acid