Target type: biologicalprocess
The chemical reactions and pathways resulting in the formation of UTP, uridine (5'-)triphosphate. [ISBN:0198506732]
The biosynthesis of uridine 5'-triphosphate (UTP) is a crucial metabolic pathway in all living organisms. UTP serves as a precursor for RNA synthesis, nucleotide sugar synthesis for glycosylation reactions, and various other cellular processes. The biosynthesis of UTP involves a series of enzymatic reactions that convert the nucleotide uridine monophosphate (UMP) into UTP.
**Step 1: UMP Kinase (UMPK) converts UMP to UDP**
UMP kinase (UMPK) catalyzes the phosphorylation of UMP to uridine 5'-diphosphate (UDP) using ATP as the phosphate donor. This reaction is reversible and is driven by the hydrolysis of ATP.
**Step 2: Nucleoside Diphosphate Kinase (NDPK) converts UDP to UTP**
Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that catalyzes the transfer of a phosphate group from ATP to UDP, generating UTP. NDPK is highly specific for nucleoside diphosphates and can utilize other nucleoside diphosphates as substrates.
**Overall Reaction:**
UMP + 2 ATP → UTP + 2 ADP
**Regulation of UTP Biosynthesis:**
The biosynthesis of UTP is tightly regulated to meet the cellular demand for this essential nucleotide. Several factors influence the activity of UMPK and NDPK, including:
* **Substrate availability:** The concentration of UMP and ATP influences the activity of both UMPK and NDPK.
* **Product inhibition:** UTP can inhibit the activity of UMPK, providing feedback regulation of the pathway.
* **Cellular energy status:** The availability of ATP influences the overall rate of UTP biosynthesis.
**Importance of UTP Biosynthesis:**
The biosynthesis of UTP is essential for various cellular processes, including:
* **RNA synthesis:** UTP is a key building block for RNA molecules, which are involved in protein synthesis, gene regulation, and other cellular processes.
* **Nucleotide sugar synthesis:** UTP is a precursor for the synthesis of nucleotide sugars, such as UDP-glucose and UDP-galactose, which are essential for glycosylation reactions.
* **Other cellular processes:** UTP is involved in various other cellular processes, including signal transduction, cell signaling, and the regulation of enzyme activity.
**Disruption of UTP Biosynthesis:**
Defects in UTP biosynthesis can lead to various diseases, including:
* **Inherited metabolic disorders:** Genetic mutations in UMPK or NDPK can cause severe metabolic disorders.
* **Cancer:** Increased UTP biosynthesis can contribute to the growth and proliferation of cancer cells.
* **Neurological disorders:** Dysregulation of UTP biosynthesis has been implicated in some neurological disorders.
In summary, the biosynthesis of UTP is a fundamental metabolic pathway that is essential for various cellular processes. The pathway is tightly regulated to maintain appropriate levels of UTP, and disruptions in the pathway can lead to various diseases.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| CAD protein | A multifunctional protein CAD that is encoded in the genome of human. [PRO:DNx, UniProtKB:P27708] | Homo sapiens (human) |
| Nucleoside diphosphate kinase B | A nucleoside diphosphate kinase B that is encoded in the genome of human. [PRO:DAN, UniProtKB:P22392] | Homo sapiens (human) |
| Nucleoside diphosphate kinase A | A nucleoside diphosphate kinase A that is encoded in the genome of human. [PRO:DNx, UniProtKB:P15531] | Homo sapiens (human) |
| Putative nucleoside diphosphate kinase | A protein that is a translation product of the NME2P1 gene in human. [PRO:DNx, UniProtKB:O60361] | Homo sapiens (human) |
| Nucleoside diphosphate kinase, mitochondrial | A nucleoside diphosphate kinase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00746] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| ureidosuccinic acid | N-carbamoylaspartic acid : An N-carbamoylamino acid that is aspartic acid with one of its amino hydrogens replaced by a carbamoyl group. ureidosuccinic acid: RN given refers to (DL)-isomer | aspartic acid derivative; C4-dicarboxylic acid; N-carbamoyl-amino acid | Escherichia coli metabolite; human metabolite; Saccharomyces cerevisiae metabolite |
| balsalazide | balsalazide : A monohydroxybenzoic acid consisting of 5-aminosalicylic acid (mesalazine) linked to 4-aminobenzoyl-beta-alanine via an azo bond. balsalazide: a mesalamine 5-aminosalicylate prodrug; 99% of ingested drug remains intact through the stomach and is delivered to and activated in the colon; used for inflammatory bowel disease, ulcerative colitis and radiation-induced proctosigmoiditis but avoided in patients with known hypersensitivity reaction to salicylates or mesalamine; structure in first source | ||
| thymidine 5'-diphosphate | dTDP : A thymidine phosphate having a diphosphate group at the 5'-position. thymidine 5'-diphosphate: see also record for thymidine 3',5'-diphosphate, RN 2863-04-9 | pyrimidine 2'-deoxyribonucleoside 5'-diphosphate; thymidine phosphate | Escherichia coli metabolite; mouse metabolite |
| alvocidib | alvocidib : A synthetic dihydroxyflavone that is 5,7-dihydroxyflavone which is substituted by a 3-hydroxy-1-methylpiperidin-4-yl group at position 8 and by a chlorine at the 2' position (the (-)-3S,4R stereoisomer). A cyclin-dependent kinase 9 (CDK9) inhibitor, it has been studied for the treatment of acute myeloid leukaemia, arthritis and atherosclerotic plaque formation. alvocidib: structure given in first source | dihydroxyflavone; hydroxypiperidine; monochlorobenzenes; tertiary amino compound | antineoplastic agent; antirheumatic drug; apoptosis inducer; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor |
| saracatinib | aromatic ether; benzodioxoles; diether; N-methylpiperazine; organochlorine compound; oxanes; quinazolines; secondary amino compound | anticoronaviral agent; antineoplastic agent; apoptosis inducer; autophagy inducer; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; radiosensitizing agent | |
| vx 702 | VX 702: a p38 MAP kinase inhibitor | phenylpyridine | |
| chir-265 | aromatic ether | ||
| pf-562,271 | indoles | ||
| buparlisib | NVP-BKM120: a pan class I PI3 kinase inhibitor with antineoplastic activity; structure in first source | aminopyridine; aminopyrimidine; morpholines; organofluorine compound | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| pha 848125 | N,1,4,4-tetramethyl-8-((4-(4-methylpiperazin-1-yl)phenyl)amino)-4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline-3-carboxamide: a cyclin dependent kinase inhibitor | ||
| gdc 0941 | pictrelisib : A sulfonamide composed of indazole, morpholine, and methylsulfonyl-substituted piperazine rings bound to a thienopyrimidine ring. | indazoles; morpholines; piperazines; sulfonamide; thienopyrimidine | EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| cudc 101 | 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide: a histone deacetylase inhibitor; structure in first source | ||
| mln 8237 | MLN 8237: an aurora kinase A inhibitor | benzazepine | |
| pci 32765 | ibrutinib : A member of the class of acrylamides that is (3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine in which the piperidine nitrogen is replaced by an acryloyl group. A selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase, it is used for treatment of B-cell malignancies. ibrutinib: a Btk protein inhibitor | acrylamides; aromatic amine; aromatic ether; N-acylpiperidine; pyrazolopyrimidine; tertiary carboxamide | antineoplastic agent; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor |
| tak 733 | |||
| entrectinib | entrectinib : A member of the class of indazoles that is 1H-indazole substituted by [4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino)benzoyl]amino and 3,5-difluorobenzyl groups at positions 3 and 5, respectively. It is a potent inhibitor of TRKA, TRKB, TRKC, ROS1, and ALK (IC50 values of 0.1 to 1.7 nM), and used for the treatment of NTRK, ROS1 and ALK gene fusion-positive solid tumours. entrectinib: inhibits TRK, ROS1, and ALK receptor tyrosine kinases; structure in first source | benzamides; difluorobenzene; indazoles; N-methylpiperazine; oxanes; secondary amino compound; secondary carboxamide | antibacterial agent; antineoplastic agent; apoptosis inducer; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
| gsk 2126458 | omipalisib : A member of the class of quinolines that is quinoline which is substituted by pyridazin-4-yl and 5-[(2,4-difluorobenzene-1-sulfonyl)amino]-6-methoxypyridin-3-yl groups at positions 4 and 6, respectively. It is a highly potent inhibitor of PI3K and mTOR developed by GlaxoSmithKline and was previously in human phase 1 clinical trials for the treatment of idiopathic pulmonary fibrosis and solid tumors. omipalisib: inhibitor of mTOR protein | aromatic ether; difluorobenzene; pyridazines; pyridines; quinolines; sulfonamide | anticoronaviral agent; antineoplastic agent; autophagy inducer; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; mTOR inhibitor; radiosensitizing agent |
| gsk 1363089 | GSK 1363089: a multikinase inhibitor that acts on Met, RON, Axl, and VEGFR; structure in first source | aromatic ether | |
| osimertinib | osimertinib : A member of the class of aminopyrimidines that is 4-(1-methylindol-3-yl)pyrimidin-2-amine in which one of the amino hydrogens is replaced by a 2-methoxy-4-[2-(dimethylamino)ethyl](methyl)amino-5-acrylamidophenyl group. Used (as the mesylate salt) for treatment of EGFR T790M mutation positive non-small cell lung cancer. osimertinib: an EGFR tyrosine kinase inhibitor | acrylamides; aminopyrimidine; biaryl; indoles; monomethoxybenzene; secondary amino compound; secondary carboxamide; substituted aniline; tertiary amino compound | antineoplastic agent; epidermal growth factor receptor antagonist |