DHODH Antibodies

Background

The DHODH gene encodes dihydroorotate dehydrogenase, which is located in the inner mitochondrial membrane and is a key oxidase in the de novo synthesis pathway of pyrimidine nucleotides. It catalyzes the conversion of dihydroorotate to orotate, maintaining the stability of the intracellular pyrimidine pool and thereby supporting basic life activities such as DNA and RNA synthesis. In rapidly proliferating cells (such as immune cells and tumor cells), the activity of DHODH is significantly upregulated, making it an important target for the treatment of autoimmune diseases and cancer. This gene was first identified in the 1970s, and its protein structure was resolved through crystallographic techniques in the 2000s, facilitating the development and application of related inhibitors (such as leflunomide). In-depth studies on the function and regulatory mechanism of DHODH have continuously promoted the development of fields such as cell metabolism, proliferation regulation, and targeted drug development.

Structure Function Application Advantage Our Products

Structure of DHODH

The dihydroxyacetone phosphate dehydrogenase encoded by the DHODH gene is a flavin-dependent mitochondrial enzyme with a molecular weight of approximately 42 kDa. There are slight differences in its molecular weight among different species, mainly due to the variations in the length and composition of the N-terminal mitochondrial targeting sequence.

Species	Human	Mouse	Rat	Yeast (S. cerevisiae)
Molecular Weight (kDa)	~42	~41.5	~42	~43
Primary Structural Differences	Contains an N-terminal mitochondrial targeting sequence and two domains	The N-terminal sequence is slightly different, but the function is highly conserved	The overall structure is highly similar to that of humans	Structure similar to mammals, but low sequence homology

The human DHODH protein consists of 394 amino acids and folds into two main domains: an N-terminal α-helical bundle domain that anchors to the inner mitochondrial membrane; and a C-terminal (α/β)8 barrel-shaped catalytic domain. The catalytic domain is tightly bound to a flavin mononucleotide (FMN) cofactor at its center, serving as an electron transfer agent for the redox reaction, which is the reason for the enzyme's yellow color. Its active site is located at the center of the barrel structure, composed of highly conserved amino acid residues, which binds the substrate dihydroxycomitrate and transfers electrons through the electron transfer chain to ubiquinone to complete the oxidation reaction.

Fig. 1 DHODH and mitochondrial respiratory chain.¹

Key structural properties of DHODH:

Double-domain configuration
Hydrophobic active pocket
Flavin mononucleotide (FMN) cofactor
Arginine and serine residue cluster

Functions of DHODH

The main function of the DHODH gene is to catalyze the key oxidation reactions in the pyrimidine biosynthesis pathway. At the same time, it is deeply involved in a wide range of physiological and pathological processes such as cell proliferation regulation and redox homeostasis maintenance.

Function	Description
Pyrimidine de novo synthesis	In the mitochondria, it catalyzes the oxidation of dihydroorotate to orotate, which is the only oxidation step in the synthesis of uridine monophosphate (UMP), providing raw materials for DNA/RNA synthesis.
Cellular Proliferation Regulation	By controlling the level of the pyrimidine pool, it directly affects the replication ability of "rapidly proliferating cells" (such as activated T cells and cancer cells), making it an important target for immune regulation and cancer treatment.
Redox Coupling	In the catalytic reaction, electrons are transferred from the FMN cofactor to ubiquinone (CoQ), directly connecting pyrimidine synthesis with the electron transfer of the mitochondrial respiratory chain.
Mitochondrial Function Regulation	Its activity affects the redox state and membrane potential of mitochondria, and is closely related to diseases associated with mitochondrial dysfunction (such as heart failure, neurodegenerative diseases).
Inflammation and Immune Response	It is expressed at higher levels in activated immune cells. Inhibitors (such as leflunomide) can effectively suppress the "excessive immune response" by blocking its function, and are used to treat autoimmune diseases such as rheumatoid arthritis.

The catalytic efficiency of DHODH is regulated by the ratio of ubiquinone to ubiquinol within the mitochondria, which makes its activity closely linked to the energy metabolism and oxidative stress state of the cell. This is the structural basis for it to function as a metabolic checkpoint molecule.

Applications of DHODH and DHODH Antibody in Literature

1. Zhou, Yue, et al. "DHODH and cancer: promising prospects to be explored." Cancer & metabolism 9.1 (2021): 22. https://doi.org/10.1186/s40170-021-00250-z

The article indicates that human dihydrolactalate dehydrogenase (DHODH) is a new target for tumor treatment, involved in pyrimidine synthesis and mitochondrial respiratory chain. Its inhibitors have shown potential in cancer treatment, providing a new strategy for clinical translation.

2. Luganini, Anna, et al. "DHODH inhibitors: What will it take to get them into the clinic as antivirals?." Antiviral Research (2025): 106099. https://doi.org/10.1016/j.antiviral.2025.106099

The article indicates that targeting human DHODH is a new broad-spectrum antiviral strategy, exerting a triple effect by inhibiting pyrimidine synthesis, activating innate immunity, and regulating inflammation. In view of the limitations of its monotherapy efficacy, it is necessary to explore combination therapy regimens in the future to promote clinical application.

3. Mullen, Nicholas J., et al. "DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation." Elife 12 (2024): RP87292.https://doi.org/10.7554/eLife.87292

The article indicates that the DHODH inhibitor Brequinar upregulates cancer cell antigen presentation through pyrimidine. When used in combination with immune checkpoint blockade, it can significantly enhance synergistic effects, providing a new strategy for clinical combination therapy.

4. Shir, Jui-Chia, et al. "DHODH Blockade Induces Ferroptosis in Neuroblastoma by Modulating the Mevalonate Pathway." Molecular & Cellular Proteomics 24.7 (2025): 101014. https://doi.org/10.1016/j.mcpro.2025.101014

This study reveals that targeting DHODH can induce ferroptosis in neuroblastoma. The mechanism involves inhibiting the activity of SQLE enzyme and reprogramming lipid metabolism, providing a novel metabolic intervention strategy for the treatment of this childhood solid tumor.

5. Amos, Alvan, et al. "The Warburg effect modulates DHODH role in ferroptosis: a review." Cell Communication and Signaling 21.1 (2023): 100. https://doi.org/10.1186/s12964-022-01025-9

This study reveals that DHODH inhibits ferroptosis by supplementing mitochondrial GPX4, and its inhibitor can block pyrimidine synthesis and promote tumor ferroptosis. This effect is influenced by the Warburg effect and GSH metabolism, providing a new idea for the design of anti-cancer drugs.

Creative Biolabs: DHODH Antibodies for Research

Creative Biolabs specializes in the production of high-quality DHODH antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom DHODH Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our DHODH antibodies, custom preparations, or technical support, contact us at email.

Reference

Zhou, Yue, et al. "DHODH and cancer: promising prospects to be explored." Cancer & metabolism 9.1 (2021): 22. https://doi.org/10.1186/s40170-021-00250-z