Target type: biologicalprocess
The chemical reactions and pathways involving uracil, 2,4-dioxopyrimidine, one of the pyrimidine bases occurring in RNA, but not in DNA. [GOC:go_curators]
Uracil metabolism is a fundamental biological process that involves the synthesis, degradation, and salvage of uracil, a pyrimidine base that is a key component of RNA. This process is crucial for maintaining the integrity of nucleic acids, which play critical roles in cellular function and heredity.
**Uracil Synthesis:**
Uracil is synthesized de novo from aspartate and carbamoyl phosphate. This process involves a series of enzymatic reactions catalyzed by aspartate transcarbamylase, dihydroorotase, and orotate phosphoribosyltransferase. The end product of this pathway is UMP (uridine monophosphate), the precursor to all other uracil nucleotides.
**Uracil Degradation:**
Uracil is degraded via the pyrimidine catabolic pathway. This pathway begins with the conversion of uracil to dihydrouracil by dihydropyrimidine dehydrogenase (DPD). Dihydrouracil is then further degraded to β-alanine and β-aminoisobutyrate. These byproducts are subsequently metabolized to other compounds.
**Uracil Salvage:**
Salvage pathways provide an alternative route for the production of uracil nucleotides. Uracil can be directly salvaged from the environment or from the breakdown of RNA. The salvage pathway involves the conversion of uracil to UMP by uracil phosphoribosyltransferase (UPRT).
**Regulation of Uracil Metabolism:**
Uracil metabolism is tightly regulated to ensure the optimal levels of uracil nucleotides for cellular processes. Regulation occurs at multiple levels, including:
- **Enzyme activity:** The activities of key enzymes involved in uracil metabolism are subject to allosteric regulation. For example, aspartate transcarbamylase is inhibited by CTP (cytidine triphosphate) and activated by ATP (adenosine triphosphate).
- **Gene expression:** The expression of genes encoding enzymes involved in uracil metabolism is regulated by various transcription factors.
- **Nutrient availability:** The availability of nutrients, such as aspartate and carbamoyl phosphate, can affect the rate of uracil synthesis.
**Clinical Significance:**
Disruptions in uracil metabolism can lead to various diseases, including:
- **Hereditary orotic aciduria:** A rare genetic disorder caused by deficiencies in the enzymes involved in uracil biosynthesis.
- **Cancer:** Uracil metabolism plays a role in the development and progression of certain cancers.
- **Immune system disorders:** Uracil metabolism is involved in the function of the immune system.
**Conclusion:**
Uracil metabolism is a complex and essential process that plays a vital role in cellular function and homeostasis. Understanding this process is crucial for developing new therapies for diseases associated with dysregulated uracil metabolism.'
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Protein | Definition | Taxonomy |
---|---|---|
Thymidylate synthase | A thymidylate synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P04818] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
phenolphthalein | Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. | phenols | |
trimethoprim | trimethoprim : An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge. Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported. | aminopyrimidine; methoxybenzenes | antibacterial drug; diuretic; drug allergen; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; environmental contaminant; xenobiotic |
1,8-naphthalenedicarboxylic acid anhydride | 1,8-naphthalenedicarboxylic acid anhydride: used as seed protector from herbicides | cyclic dicarboxylic anhydride | |
fluorodeoxyuridylate | Fluorodeoxyuridylate: 5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine. | pyrimidine 2'-deoxyribonucleoside 5'-monophosphate | |
2'-deoxyuridylic acid | 2'-deoxyuridylic acid: RN given refers to parent cpd | deoxyuridine phosphate; pyrimidine 2'-deoxyribonucleoside 5'-monophosphate | Escherichia coli metabolite; metabolite; mouse metabolite |
dansyl hydrazine | |||
methotrexate | dicarboxylic acid; monocarboxylic acid amide; pteridines | abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent | |
n-(4-(n-((2,4-diaminofuro(2,3-d)pyrimidin-5-yl)methyl)amino)benzoyl)glutamic acid | N-(4-(N-((2,4-diaminofuro(2,3-d)pyrimidin-5-yl)methyl)amino)benzoyl)glutamic acid: structure given in first source | ||
n-4-hydroxy-2'-deoxycytidylic acid | N-4-hydroxy-2'-deoxycytidylic acid: reversibly binds to thymidylate synthetase | ||
flavin mononucleotide | flavin mononucleotide; vitamin B2 | bacterial metabolite; coenzyme; cofactor; human metabolite; mouse metabolite | |
folic acid | folcysteine: used to promote fertility in chickens vitamin B9 : Any B-vitamin that exhibits biological activity against vitamin B9 deficiency. Vitamin B9 refers to the many forms of folic acid and its derivatives, including tetrahydrofolic acid (the active form), methyltetrahydrofolate (the primary form found in blood), methenyltetrahydrofolate, folinic acid amongst others. They are present in abundance in green leafy vegetables, citrus fruits, and animal products. Lack of vitamin B9 leads to anemia, a condition in which the body cannot produce sufficient number of red blood cells. Symptoms of vitamin B9 deficiency include fatigue, muscle weakness, and pale skin. | folic acids; N-acyl-amino acid | human metabolite; mouse metabolite; nutrient |
raltitrexed | N-acyl-amino acid | ||
nolatrexed | nolatrexed: structure given in first source; RN given refers to dihydrochloride | ||
ici 198583 | ICI 198583: RN & structure given in first source | ||
n-(4(n-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)benzoyl)-l-glutamic acid | |||
1843u89 | 1843U89: structure given in first source; a folate analog | ||
5,11-methenyltetrahydrohomofolate | |||
pemetrexed | pemetrexed disodium : An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). | N-acyl-L-glutamic acid; pyrrolopyrimidine | antimetabolite; antineoplastic agent; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; EC 2.1.1.45 (thymidylate synthase) inhibitor; EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor |
n(10)-methylfolate | folic acids | ||
cb 3717 | N-acyl-L-glutamic acid | ||
cb 30865 | |||
ag 85 | AG 85: structure given in first source | ||
cb 3705 | CB 3705: inhibitor of dihydrofolate reductase & thymidylate synthetase | ||
2-desamino-2-methyl-5,8-dideazaisofolic acid | 2-desamino-2-methyl-5,8-dideazaisofolic acid: structure given in first source | ||
(5)n,(8)n-deaza-(10)-n-methylfolate | (5)N,(8)N-deaza-(10)-N-methylfolate: structure |