Methylenetetrahydrofolate Reductase Deficiencies

A project by Jennifer Stanley & Elizabeth Garrett

Bios364--Molecular Genetics

Dr. Chet Fornari, Professor

DePauw University

May 10,  2001

Human methylenetetrahydrofolate reductase (MTHFR) is a key cytoplasmic enzyme in the folate metabolism pathway (Figure 1).  It utilizes the cofactor flavin adenine dinucleotide (FAD) and substrate NADPH to catalyze the conversion of 5,10-methylenetetrahydrofolate (CH2-H4folate) to 5-methyltetrahydrofolate (CH3-H4folate):

CH2-H4folate  +  NADPH    CH3-H4folate  +  NADP +

The CH3-H4folate product is then used by methionine synthase as a methyl donor in the reaction converting homocysteine to methionine.  Any failure of MTHFR to adequately perform its reaction causes a low supply of this necessary methyl donor and leads to a build-up of homocysteine. 

Several conditions have been linked to a deficiency in MTHFR.  The purpose of this web page is to describe the genetic, molecular, and biochemical basis of these conditions.   Please select a topic from the links below to learn all about it!!

Folate pathway Initial Discovery Clinical Aspects Gene Cloning Chromosome Locus Gene Structure Inheritance Mutation & Frequency Protein Properties Diagnosis&Treatment Works Cited MTHFR Links