Name: China Supplier High Quality Best Price 1-Methyl-L-4,5-dihydroorotic acid CAS 103365-69-1
Brand: Wuhan Fortuna Chemical Co., Ltd.

1-Methyl-L-4,5-dihydroorotic acid is a synthetic, non-natural analog of a key biological intermediate in the de novo biosynthesis of pyrimidine nucleotides (which are the building blocks of RNA and DNA). Its primary significance is as a specific inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH).

1. Breaking Down the Name

To understand what it is, let's dissect its name:

Orotic acid: A natural compound (vitamin B13) and a central intermediate in the pyrimidine biosynthesis pathway.
4,5-Dihydroorotic acid: This is the immediate biological precursor to orotic acid. It is the substrate for the enzyme DHODH, which converts it to orotic acid.
1-Methyl: This indicates a methyl group (-CH₃) has been attached to the nitrogen atom at the 1-position of the dihydroorotic acid ring. This modification is not found in the natural molecule.
L-: This refers to the specific three-dimensional stereochemistry (spatial arrangement) of the molecule, which is the same as the natural, biologically active form.

In essence, it is a slightly modified version of the natural substrate (dihydroorotic acid).

2. Biological Context and Function: The Pyrimidine Pathway

To understand its role, we need to look at the pathway it interrupts:

The de novo pyrimidine biosynthesis pathway is a multi-step process to build uracil, cytosine, and thymine nucleotides. A crucial step is the oxidation of dihydroorotate to orotate, catalyzed by the enzyme dihydroorotate dehydrogenase (DHODH).

1-Methyl-L-4,5-dihydroorotic acid is designed to mimic the natural substrate, dihydroorotate. It binds very tightly to the active site of the DHODH enzyme but cannot be processed. By occupying the enzyme's active site, it competitively inhibits DHODH, bringing the entire pyrimidine biosynthesis pathway to a halt.

3. Key Uses and Significance

Scientific Research: It is a classic and specific tool used in biochemistry and cell biology labs to:

Study the pyrimidine biosynthesis pathway.
Probe the function of DHODH.
Arrest cell proliferation in experiments. Since rapidly dividing cells (e.g., immune cells, cancer cells) have a high demand for nucleotides, inhibiting DHODH effectively stops their growth and division.
Validate the mechanism of action of other DHODH inhibitors.

DHODH as a Drug Target: The discovery that this compound inhibits DHODH highlighted the enzyme's importance and validated it as a potential drug target for diseases involving hyperproliferative cells.

Autoimmune Diseases: The drug Leflunomide (and its active metabolite Teriflunomide) is a well-known DHODH inhibitor used to treat diseases like rheumatoid arthritis and multiple sclerosis. It works by inhibiting pyrimidine synthesis in overactive immune cells, thereby suppressing the immune response.
Cancer: DHODH inhibitors are being investigated for their potential as anti-cancer therapies.
Antiviral and Antimicrobial: Some viruses and parasites rely heavily on the host's pyrimidine pathway, making DHODH a potential target for infectious disease drugs.

4. Properties

Solubility: It is typically soluble in water and aqueous buffers.
Stability: It should be stored as recommended, usually at -20°C, to maintain stability over time.

Analogy

Think of the DHODH enzyme as a very specific lock, and its natural substrate (dihydroorotate) is the correct key that fits and turns. 1-Methyl-L-4,5-dihydroorotic acid is like a key that fits into the lock perfectly but has been slightly altered so it cannot turn. It jams the lock, preventing the correct key from entering and doing its job.

In a Nutshell:

1-Methyl-L-4,5-dihydroorotic acid is not a natural metabolite but a purpose-built biochemical tool. Its main function is to potently and specifically inhibit the enzyme DHODH, which is a crucial step in making the building blocks for RNA and DNA. This makes it invaluable for research and has helped establish DHODH as an important target for drugs treating autoimmune diseases and cancer.