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The mysterious power of dihydrofolate reductase: How does it affect cell growth?
In the basic construction of life, dihydrofolate reductase (DHFR) plays an indispensable role. This enzyme is responsible for converting dihydrofolate into tetrahydrofolate, which affects the cell's ability to grow and reproduce. With in-depth research on this enzyme, scientists have gradually uncovered its profound impact on cell growth.
"Dihydrofolate reductase is considered a key control point in cellular metabolism."
DHFR exists in similar structures in humans and other organisms, making it a focus of research. The DHFR gene located on chromosome 5 is responsible for the production of this enzyme and plays a key role in cell metabolism. Its main function is responsible for the synthesis of tetrahydrofolate, which is essential for the removal of newly synthesized purines, thymidylate and certain amino acids.
Tetrahydrofolate and its derivatives play an important role in regulating nucleic acid synthesis within cells. This further confirmed the necessity of DHFR for cell growth when mutant cells lacking DHFR were found to require other components such as glycine and thymidine to survive. In further studies, this enzyme was also shown to play a role in the recovery of tetrahydrobiopterin from dihydrobiopterin.
"The active site of DHFR contains a central structure composed of eight antiparallel β-strands connected by spaced α-helices."
Structurally, the main feature of DHFR is its eight antiparallel β-strands, which provide support and flexibility for its function. This allows DHFR to rapidly adjust its shape to more efficiently catalyze the conversion of dihydrofolate. Its catalytic mechanism involves the transfer of hydrogen provided by NADPH to dihydrofolate, and the Pro-Trp dipeptide plays an important role in this process.
The catalytic cycle of DHFR relies on several key intermediates, and changes in shape are crucial to its catalytic process. During the catalytic process, the opening and closing of the Met20 loop can affect the binding of substrates and the release of products, which has a direct impact on cell reproduction and growth.
"DHFR mutations may lead to dihydrofolate reductase deficiency, leading to rare folate metabolism disorders."
Clinically, DHFR mutations can lead to dihydrofolate reductase deficiency, a rare genetic disorder that may result in megaloblastic anemia and other health problems. These conditions can be corrected by supplementing with reduced forms of folic acid, such as the amino acid folate.
The therapeutic application of DHFR has also attracted widespread attention. Due to its central role in the synthesis of DNA precursors, many drugs such as methotrexate and TRIMETHOPRIM are designed to inhibit this enzyme, thereby limiting the growth of cancer cells. In addition, inhibition of DHFR can also effectively target bacterial infections, showing its potential in antibiotic development.
In cancer treatment, DHFR is considered a major target because of its direct impact on leucovorin levels. Eye-catching research shows that a range of treatment options focus on inhibiting DHFR activity to prevent tumor expansion and growth.
"Studies in patients with colorectal cancer show that combination with 5-fluorouracil and doxorubicin may extend survival."
For the treatment of infections, bacterial-specific DHFR inhibitors such as TRIMETHOPRIM have demonstrated activity against a variety of Gram-positive bacteria, but resistance has emerged over time, reminding the fragility and evolution of drug systems.
In addition, BHDFR is also considered to have potential applications in the treatment of anthrax, making it a hot topic in current research. With its special structure, the enzyme is less sensitive to antibiotic resistance in other species and has higher catalytic efficiency.
In experimental studies, DHFR is used as a tool to detect protein interactions. Its use in CHO cells has become a new way to produce recombinant proteins. These cells can only grow in an environment lacking thymidine, further promoting their application and exploration by scientists.
Research on dihydrofolate reductase not only reveals its key role in cell growth, but also demonstrates its diversified application potential in medical treatment and scientific research. So will future medical advances depend on further research on this enzyme?
