| Term | Definition |
|---|
| CO2, aspartate, glutamine | building blocks of pyrimidines |
| second | all ring atoms are present after ____ step |
| after the ring is formed | in contrast to purine synthesis, ribose is added _______ |
| PRPP. | The source of the ribose in pyrimidine biosynthesis |
| UTP, CTP, and TMP. | The three major end products of pyrimidine biosynthesis |
| carbamoyl phosphate synthetase II | enzyme of step 1 |
| orotic acid | first pyrimidine |
| OMP - orotidine monophosphate | first pyrimidine nucleotide |
| UMP | first major end product of pyrimidine biosynthesis |
| 3 | first __ enzymes part of a single protein |
| CPS II, ATC, DHO | enzymes of CAD |
| orotate phosphoribosyl transferase and orotidylic acid decarboxylase (UMP synthase) | enzymes of UMP synthase |
| glutamine | UTP => CTP : amino donor |
| Ribonucleotide reductase- | UDP => dUDP : enzyme |
| thymidylate synthase | dUMP => TMP: enzyme |
| UTP on carbamoyl phosphate synthetase II | feedback inhibition of pyrimidine biosynthesis |
| Compartmentation: two pools of carbamoyl phosphate in mito and cytosol. Metabolic channeling: first three steps catalyzed by same protein, CAD. | feedback inhibition limited to CPS II and not CPS I |
| , carbamoyl phosphate synthetase II, | committed step of pyrimidine biosynthesis |
| CTP synthetase | _____________ uses glutamine as the amino donor and is inhibited by glutamine analogs |
| 5-fluorouracil (5-FU) | is an effective inhibitor of thymidylate synthesis. |
| FdUMP | 5-fluorouracil is converted in the cell into ____________ |
| binds irreversibly to the active site of thymidylate synthase, thereby inactivating the enzyme and blocking thymidylate synthesis. | method of FdUMP |
| block DNA synthesis (block cell growth, cause cell death) | result of blocking thymidylate synthesis |
| CO2, NH3, beta-aminoisobutyrate | 3 end products of pyrimidine catabolism |
| beta-aminoisobutyrate | can be an indicator of DNA degredation and cell death if found in urine in high levels |
| Hereditary Orotic Aciduria | Symptoms: megaloblastic anemia, growth retardation, excess orotic acid in urine |
| Hereditary Orotic Aciduria | The primary clinical problems are due to lack of pyrimidines for DNA and RNA synthesis in rapidly dividing cells. |
| orotidine-5'-P pyrophosphorylase (orotate phosphoribosyl transferase) and orotidine-5'-P decarboxylase | Deficiency in Hereditary Orotic Aciduria |
| lack of pyrimidines for DNA and RNA synthesis in rapidly dividing cells. | The primary clinical problems in Hereditary Orotic Aciduria are due to |
| oral Uridine (which goes to UTP) | treatment for Hereditary Orotic Aciduria |
| ribonucleotide reductase | All four ribonucleotides are converted by the same enzyme |
| T=thioredoxin T(SH)2 | source of reducing power for ribonucleotide reductase |
| dATP | inhibits at the general activity site. |
| dGTP and dTTP | act as inhibitors at the specificity site, by inhibiting reduction of pyrimidine nucleoside diphosphates |
| : dTTP, from thymidine, inhibits reduction of pyrimidine nucleoside diphosphates (Pool of dCTP decreased 10-fold) | Why do high levels of thymidine arrest growth of cells? |
| Thymidylate synthase (not directly from ribonucleotide reductase like dADP, dGDP, dCDP, and dUDP) | dTMP is derived from methylation of dUMP by |
| phosphoribosyl transferase and nucleoside phosphorylase/nucleoside kinase | two types of salvage pathways |
| Adenine (APRT), Guanine/Hypoxanthine (HGPRT), Uracil (UPRT) and none of cytosine | phosphoribosyl transferases |
| HGPRT | enzyme deficient in Lesch-Nyhan |
| Lesch-Nyhan | increased uric acid with self-mutilation and mental retardation |
| brain relies upon salvage pathways for nucleotides | reason for neurological problems in Lesch-Nyhan |
| PRPP | sugar added in slavage pathways (phosphoribosyl transferase type) |
| turns it up. PRPP used for purine synthesis instead of salvage pathway | result of HGPRT deficiency on purine synthesis |
| uracil and thymine only | bases 2nd type (w/ kinase - 2 steps) of salvage pathway works with |
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