ABSTRACT
Since the initial description in 1972 by Freeman, Mudd and their colleagues [1-3], more than 40 patients have been reported with deficiency of MeFH4 reductase (EC 1.5.1.20) (MIM 236250) [4,5].
One-carbon units, critical for the synthesis of purines, thymidylate, serine and methionine, are transferred from their predominantly glycine and serine sources by way of folic acid intermediates. Entry into the pool is via 5,10-methylene FH4. This compound serves directly the synthesis of thymidylate. It is oxidized to formyl-FH4 for the de novo synthesis of purines. In the synthesis of methionine, the methylene, MeFH4 is reduced to 5-methyl-FH4 (Figure 23.1). The reductase reaction involves the conversion of the nicotinamide-adenine dinucleotide (NADPH) cofactor to NADP. The methyl-FH4 product is the donor of the methyl group to homocysteine to form methionine.
