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MBC - Lecture 53

Pyrimidine Metabolism (Mock)

Lecture 53 Pyrimidine Metabolism
UMP is the parent nucleotide for ___ and ___. CTP and dTMP
Formation of UMP is through ___ steps/reactions. 6
Not all reactions are ___ in formation of UMP. cytosolic
UMP is not built on a PRPP donated ___. ribosyl-5-phosphate
PRPP donating ribosyl-5-phosphate is the ___ step in making UMP. last
UMP is forms to ___ before making CTP. UTP
Biosynthesis of carbamoyl phosphate is by ___. CPS II
CPS II works in the ___, and uses ___. cytosol, glutamine
Regulated step in pyrimidine synthesis is ___. CPS II
CPS II is actvated by ___. PRPP
Synthesis of UMP uses two multifunctional ___. enzymes
CAD is encoded by ___ gene(s). 1 gene
Enzymes in CAD are ___, ___, and ___. Carbamoyl phosphate synthase II, aspartate transcarbamoylase, and dihydroorotase.
Enzymes in UMP synthase are ___ and ___. orotate phosphoribosyltransferase and OMP decarboxylase
___ donates C4-6 and N1 to the pyrimidine structure. Aspartate
___ donates C2 to the pyrimidine structure. HCO3- (Bicarbonate)
___ donates N3 to the pyrimidine structure. Glutamine amide
Hereditary orotic aciduria leads to anemia because of: RBC synthesis’ high demand for DNA synthesis
Hereditary orotic aciduria causes anemia and ___. growth retardation
UTP and CTP both negatively feedback to ___. CPS II
___ and ___ up-regulate CPS II. ATP and PRPP
Orotic Aciduria, Type I Defective UMP synthase (both), autosomal recessive, orotic acid crystalluria, FTT, megaloblastic anemia, immunodeficiency
Orotic Aciduria, Type II Defective UMP synthase (orotidylate decarboxylase only), autosomal recessive, orotidinuria and orotic aciduria, megaloblastic anemia, treatable with oral uridine
Ornithine Transcarbamoylase Deficiency Defective OTC, X-linked recessive, protein intolerance, hepatic encephalopathy, mild orotic acidura
UMP to UTP is through two ___ steps. phosphorylation steps (ATP donor)
CTP Synthase Catalyzes synthesis of CTP from UTP by substituting keto group for amino group
The nitrogen donor in CTP synthase is ___, releasing ___. glutamine, releasing glutamate
The phosphate donor group in CTP synthase is ___. ATP
Pyrimidine nucleosides can be salvaged by ___. ATP-requiring kinases
Pyrimidine nucleoside salvaging kinases are: uridine-cytidine kinase, thymidine kinase, deoxycytidine kinase
Nucleoside 5’-Diphosphate Reductase (Ribonucleotide Reductase) Catalyzes synthesis of 2’-deoxyribonucleotide from ribonucleotide (DNA to RNA)
___, ___, and ___ can be formed directly from its precursors by ribonucleotide reductase and phosphorylation. dATP, dGTP, and dCTP
dTTP is not directly synthesized to prevent: accidental incorporation of dUDP into DNA
Synthesis of dTTP can be from precursors ___ or ___. CDP or UDP
CDP → ___ → ___ → ___ → ___ →→ dTTP CDP →dCDP → dCMP → dUMP → dTMP →→ dTTP
UDP → ___ → ___ → ___ →→ DTTP UDP → dUDP → dUMP → dTMP →→ dTTP
Thymidylate Synthase Catalyzes synthesis dTMP from dUMP, requires tetrahydrofolate
Pyrimidine analogs can block ___. DNA synthesis
Cytosine Arabinoside Leukemia & non-Hodkin lymphoma therapy, AraC → AraCMP → AraCTP into DNA, inhibits strand elongation
3’-azido-3’-deoxythymidine (AZT) AZT triphosphate, inhibits HIV DNA polymerase
Methotrexate is a structural analog of ___. folic acid
Methotrexate inhibits ___. dihydrofolate reductase (synthesis of dihydrofolate from folate or regeneration of dihyrdofolate to tetrahydrofolate)
___ cells are especially sensitive to dihyrdofolate reductase inhibitors (i.e. methotrexate). Dividing
β-aminoisobutyrate excretion measures ___. DNA breakdown
Created by: emyang