DHFR gene

The human DHFR gene is part of the folate family of genes, meaning it works to process folate that gets delivered through the MTHFR gene. The human DHFR gene, which encodes the enzyme human dihydrofolate reductase, is also connected directly to the Biopterin cycle so it can affect both physical and mental health.

Once the folates pass through the FOLR genes (folate receptor genes), folates get converted to Dihydrofolate (DHF) via the DHFR genes (in Red) above.

In addition, the gene DHFR, which is part of the folate family of genes (MTHFR), is directly connected to the folate receptor, that feeds the biopterin cycle in your brain.

When the folate receptor is compromised (as per the image below showing homozygous or double copies of the DHFR gene mutation) and the DHFR has mutations and or is compromised with folic acid, ECGC, GSE and or radiation, the side effect is the disruption of making biopterin and neurotransmitters properly, essentially blocking the ability to feeling happy and healthy mentally.

Because the DHFR gene works directly in the folate process, symptoms of a compromised or gene mutation in DHFR can look like a MTHFR gene problem or a folate deficiency as per the following symptoms:

Introduction

Dihydrofolate reductase (DHFR) is an enzyme that plays a crucial role in folate metabolism, a process essential for the synthesis of nucleic acids and amino acids. The DHFR gene, located on chromosome 5, encodes for the DHFR enzyme, which is responsible for the reduction of dihydrofolate to tetrahydrofolate. Tetrahydrofolate is a crucial cofactor for the synthesis of nucleic acids and amino acids. In this article, we will discuss the biological context, function and structure, clinical significance, diagnosis and treatment, and research and future directions of the DHFR gene.

Biological Context

The DHFR gene is a key player in the folate metabolism pathway, which is vital for the synthesis of nucleic acids and amino acids. This pathway begins with the conversion of folic acid to dihydrofolate, which is then reduced to tetrahydrofolate by the DHFR enzyme. Tetrahydrofolate acts as a cofactor in various biochemical reactions, including the synthesis of nucleic acids and amino acids. The DHFR gene is expressed in various tissues, including peripheral blood, underscoring its essential role in maintaining normal cellular function.

Folate Metabolism and the DHFR Gene

Folate metabolism is a cornerstone of human health, and the dihydrofolate reductase (DHFR) gene is pivotal in this intricate pathway. The DHFR gene encodes the enzyme dihydrofolate reductase, which is essential for converting dihydrofolate into tetrahydrofolate. This conversion is crucial because tetrahydrofolate acts as a cofactor in the synthesis of nucleic acids and amino acids, the building blocks of our DNA and proteins.

Located on chromosome 5, the DHFR gene comprises six exons and is highly conserved across different species, underscoring its fundamental role in biology. In mammalian cells, the expression of the DHFR gene is tightly regulated to ensure proper cellular function. When this regulation falters, it can lead to dihydrofolate reductase deficiency, a rare genetic disorder marked by impaired folate metabolism. This deficiency manifests in severe conditions such as megaloblastic anemia, cerebral folate deficiency, and significant neurological diseases.

Moreover, the DHFR gene is linked to various cancers, including breast, colorectal, lung, and leukemia. Gene polymorphisms, particularly single nucleotide polymorphisms (SNPs), in the DHFR gene can alter the enzyme’s expression and function, thereby affecting folate metabolism and increasing disease risk. Understanding these polymorphisms provides valuable insights into the genetic underpinnings of folate metabolism disorders.

Interestingly, the human DHFR gene shares similarities with other dihydrofolate reductase-like genes, and its activity is regulated by multiple factors, including transcriptional and post-transcriptional mechanisms. The enzyme’s activity is also subject to feedback inhibition by tetrahydrofolate, ensuring a balanced folate metabolism pathway.

In summary, the DHFR gene is indispensable for folate metabolism, and its dysfunction can lead to a spectrum of diseases. Ongoing research is crucial to unravel the genetic basis of DHFR gene polymorphisms and their broader impact on human health.

Function and Structure

The DHFR enzyme is a 21-kDa protein composed of 187 amino acids. It has a unique structure featuring a binding site for dihydrofolate and a catalytic site for its reduction to tetrahydrofolate. This functional dihydrofolate reductase gene is indispensable for the synthesis of nucleic acids and amino acids. Additionally, the enzyme is involved in the de novo synthesis of purines and pyrimidines, which are the building blocks of DNA and RNA.

Folate (vitamin B9) deficiency or dihydrofolate reductase deficiency symptoms


  • ADD/ADHD



  • Addictive behaviors



  • Alcoholism



  • Allergies



  • Alzheimer’s



  • Anxiety



  • Autism



  • Autism



  • Bipolar



  • Cancer



  • Cardiovascular disease – Heart attack, atherosclerosis, elevated cholesterol, hypertension, stroke, fat metabolism issues



  • Chemical sensitivity



  • Chronic fatigue syndrome



  • Chronic viral infection



  • Cleft palate



  • Congenital Heart defects



  • Depression



  • Diabetes



  • Downs syndrome



  • Fibromyalgia



  • Immune deficiency



  • Infertility



  • Insomnia



  • MS (multiple sclerosis)



  • Neural tube defects



  • Neuropathy



  • Nutritional disorders (Vitamin & mineral imbalances that lead to disease)



  • Panic attacks



  • Parkinsons



  • Pulmonary embolisms



  • Recurrent miscarriage



  • Schizophrenia



  • Spina bifida



  • Electromagnetic sensitivity



  • Thyroid dysfunction


As you can see this one gene mutation can cause serious health problems, but it doesn’t stop there.  When you have a nutritional break in folate due to DHFR gene mutations, the bigger problem is that folate works with all other B complex vitamins.

As you can imagine, just having active gene mutations in DHFR can lead to a cascade of nutritional breaks in all B complex vitamins and it gets more complex, this is because B complex vitamins work with hundreds of other biochemical reactions in the body and brain.

Clinical Significance

Mutations in the DHFR gene can lead to dihydrofolate reductase deficiency, a rare genetic disorder characterized by megaloblastic anemia, cerebral folate deficiency, and severe neurological disease. The DHFR gene is also linked to various cancers, including breast cancer, colorectal cancer, lung cancer, and leukemia. Gene polymorphisms involved in the DHFR gene can affect the expression and function of the enzyme, increasing the risk of cancer.

Human DHFR gene and radiation

The DHFR gene is also susceptible to EMF radiation which is now 100 million times more prevalent today than just 100 years ago. Studies on various cell lines have shown that the DHFR gene’s susceptibility to EMF radiation can lead to significant disruptions in folate processing. This means that many people now have problems processing their folate through the DHFR gene, which has led to many mental health problems.

Diagnosis and Treatment

Diagnosis of dihydrofolate reductase deficiency typically involves genetic testing methods such as polymerase chain reaction (PCR) and DNA sequencing. Treatment often includes supplementation with folic acid and other essential nutrients to manage symptoms. In some cases, gene therapy may be explored as a means to restore normal DHFR enzyme function.

Research and Future Directions

Research on the DHFR gene and its integral role in folate metabolism is a dynamic and evolving field. Scientists are delving into several promising areas to better understand and address the implications of DHFR gene mutations.

One key research focus is the identification of novel gene polymorphisms within the DHFR gene and their associations with various diseases. By pinpointing these genetic variations, researchers aim to uncover how they influence the enzyme’s function and contribute to health conditions.

Another significant area of study involves examining DHFR expression across different cell lines and tissues. This research seeks to elucidate how the regulation of DHFR expression impacts folate metabolism and overall cellular health. Understanding these regulatory mechanisms could pave the way for new therapeutic strategies.

The development of advanced diagnostic tools and treatments for dihydrofolate reductase deficiency is also a priority. Techniques such as polymerase chain reaction (PCR) and other molecular methods are being refined to detect DHFR gene mutations more accurately, facilitating early diagnosis and intervention.

Additionally, the potential of DHFR inhibitors as therapeutic agents is being explored, particularly in the context of cancer treatment. Researchers are working on developing inhibitors that can selectively target cancer cells while sparing normal cells, offering a promising avenue for more effective and less toxic cancer therapies.

Furthermore, the study of DHFR gene polymorphisms in diverse populations is gaining traction. This research aims to understand the genetic basis of folate metabolism disorders across different genetic backgrounds, ultimately leading to the development of personalized therapies tailored to individual genetic profiles.

Overall, ongoing research on the DHFR gene is vital for deepening our understanding of the genetic factors influencing folate metabolism and for developing innovative treatments for related diseases. Continued exploration in this field holds the promise of significant advancements in medical science and improved health outcomes.

 

Russell Browne
Researched and verified by Russell Browne SNHS Dip. (Advanced Nutrition) – specialist expertise in epigenetics, and nutrigenomics (genetic mutation specialist).