SUMMARY PARAGRAPH for MET13
There are two genes in S. cerevisiae with sequence similarity to methylenetetrahydrofolate reductase (MTHFR), MET13 and MET12. MTHFR catalyzes the reduction of N5,N10-methylenetetrahydrofolate to N5-methyltetrahydrofolate. This reaction commits a methyl group from N5,N10-methylenetetrahydrofolate to the synthesis of methionine. In the subsequent reaction, the methyl group is transferred to homocysteine to produce methionine (3). Both Met12p and Met13p have been shown to have MTHFR activity in crude extracts, though for technical reasons, only the reverse reaction was assayed (3). However, by phenotypic analysis, MET13 appears to be the major or sole source of methionine biosynthetic activity in standard laboratory conditions. Disruption of MET13 causes methionine auxotrophy, while disruption of MET12 causes no detectable phenotype (3, 4). In conditions where both MET13 mRNA and Met13p activity are detectable, MET12 mRNA is detectable, but MTHFR activity from Met12p is not (3). In addition, overexpression of MET12 failed to rescue the methionine requirement of the MET13 deletion strain (3). Overexpression of the human MTHFR complements the methionine auxotrophy of met13 cells, but overexpression of the E. coli enzyme does not (3, 4).
Both MET12 and MET13 have sequence similarity to the approximately 300 amino acid catalytic domain of MTHFR from E. coli and from H. sapiens. In addition, both MET12 and MET13 share additional sequence similarity with the human MTHFR gene in the C-terminal region, which contains the binding site for S-adenosyl-methionine, which is known to regulate the human enzyme (3).
Deficiency of MTHFR is the most common genetic defect in folate metabolism in humans, resulting in hyperhomocysteinemia, homocystinuria, and hypomethionemia (3). Homocystinuria is sometimes associated with psychotic symptoms (5). Elevelated levels of homocysteine, due to MTHFR deficiency, are also associated with increased risks of vascular disease and neural tube defects (3).
In early purifications of the mitochondrial ribosome, MET13 was identified as a component of the large mitochondrial ribosomal subunit (2) and was called YmL45 (2) or MRPL45 (6). It has subsequently been shown that this was an error (7).
Last updated: 2008-08-05