Abstract
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydofolate (CH2-H4folate) to 5- methyltetrahydrofolate (CH3-H4folate). The enzyme employs a noncovalently-bound flavin adenine dinucleotide (FAD), which accepts reducing equivalents from NAD(P)H and transfers them to CH2-H4folate. The reaction provides the sole source of CH3-H4folate, which is utilized by methionine synthase in the synthesis of methionine from homocysteine. MTHFR plays a key role in folate metabolism and in the homeostasis of homocysteine; mutations in the enzyme lead to hyperhomocyst(e)inemia. A common C677T polymorphism in MTHFR has been associated with an increased risk for the development of cardiovascular disease, Alzheimer’s disease, and depression in adults, and of neural tube defects in the fetus. The mutation also confers protection for certain types of cancers. This review presents the current knowledge of the enzyme, its biochemical characterization, and medical significance.
Keywords: Flavin, FAD, folate, MTHFR, methylenetetrahydrofolate, methyltetrahydrofolate, homocysteine, C677T polymorphism
Current Pharmaceutical Design
Title:Methylenetetrahydrofolate Reductase: Biochemical Characterization and Medical Significance
Volume: 19 Issue: 14
Author(s): Elizabeth E. Trimmer
Affiliation:
Keywords: Flavin, FAD, folate, MTHFR, methylenetetrahydrofolate, methyltetrahydrofolate, homocysteine, C677T polymorphism
Abstract: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydofolate (CH2-H4folate) to 5- methyltetrahydrofolate (CH3-H4folate). The enzyme employs a noncovalently-bound flavin adenine dinucleotide (FAD), which accepts reducing equivalents from NAD(P)H and transfers them to CH2-H4folate. The reaction provides the sole source of CH3-H4folate, which is utilized by methionine synthase in the synthesis of methionine from homocysteine. MTHFR plays a key role in folate metabolism and in the homeostasis of homocysteine; mutations in the enzyme lead to hyperhomocyst(e)inemia. A common C677T polymorphism in MTHFR has been associated with an increased risk for the development of cardiovascular disease, Alzheimer’s disease, and depression in adults, and of neural tube defects in the fetus. The mutation also confers protection for certain types of cancers. This review presents the current knowledge of the enzyme, its biochemical characterization, and medical significance.
Export Options
About this article
Cite this article as:
E. Trimmer Elizabeth, Methylenetetrahydrofolate Reductase: Biochemical Characterization and Medical Significance, Current Pharmaceutical Design 2013; 19 (14) . https://dx.doi.org/10.2174/1381612811319140008
DOI https://dx.doi.org/10.2174/1381612811319140008 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Antithrombotic Therapy After TAVR
Current Vascular Pharmacology Patent Selections
Recent Patents on Cardiovascular Drug Discovery Low-Cost Anti-HIV Compounds: Potential Application for AIDS Therapy in Developing Countries
Current Pharmaceutical Design Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Assessment of Response to Treatment and Follow-Up in Gastroenteropancreatic Neuroendocrine Neoplasms
Endocrine, Metabolic & Immune Disorders - Drug Targets Molecular Pharmacological Approaches to Effects of Capsaicinoids and of Classical Antisecretory Drugs on Gastric Basal Acid Secretion and on Indomethacin-Induced Gastric Mucosal Damage in Human Healthy Subjects (Mini Review)
Current Pharmaceutical Design Human Heart Cardiomyocytes in Drug Discovery and Research: New Opportunities in Translational Sciences
Current Pharmaceutical Biotechnology Update on Anti-TNF-Alpha Treatment in Rheumatic Diseases
Current Drug Therapy Current Drugs and Nutraceuticals for the Treatment of Patients with Dyslipidemias
Current Pharmaceutical Design Cellular Membrane Microparticles: Potential Targets of Combinational Therapy for Vascular Disease
Current Vascular Pharmacology The Beneficial Role of Vitamin D in Human Immunodeficiency Virus Infection
Current HIV Research Inhibitors of Catechol-O-methyltransferase in the Treatment of Neurological Disorders
Central Nervous System Agents in Medicinal Chemistry The Management of Thymoma - A Review of the Status Quo with Practical Treatment Recommendations
Current Respiratory Medicine Reviews Immune Response to Native Lipoproteins Induces Visceral Obesity and Aortic Wall Injury in Rats: The Role of Testosterone
Endocrine, Metabolic & Immune Disorders - Drug Targets Thrombolysis in Ischemic Stroke: Focus on New Treatment Strategies
Recent Patents on Cardiovascular Drug Discovery Analytical Procedures for Secondary Metabolites Determination: Recent Trends and Future Perspectives
Letters in Drug Design & Discovery Pain Management in Hematological Patients with Major Organ Dysfunctions and Comorbid Illnesses
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial [Hot Topic: New Drug Targets for the Treatment of Asthma (Guest Editor: D. Knight)]
Current Drug Targets Aptamers: Molecular Tools for Medical Diagnosis
Current Topics in Medicinal Chemistry Novel Carriers for Coenzyme Q10 Delivery
Current Drug Delivery Reactive Oxygen Species and Antioxidants in the Pathophysiology of Cardiovascular Disease: Does the Actual Knowledge Justify a Clinical Approach?
Current Vascular Pharmacology