Nucleotide Metabolism
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Created by:
nicolie424 on February 2, 2012
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62 terms
Terms | Definitions |
|---|---|
 Purine | has a two ringed base; adenine and guanine |
| Pyrimidine | has a single ringed base; thyamine,cytosine, uracil |
| Nucleoside | base with no phosphate at the 5' end |
| Nucleotide | base with a phosphate at the 5' end |
| Purine Bases | degraded to uric acid which causes Gout at high levels |
| Pyrimidine Bases | degraded to soluble products |
| Synthesis of Nucleotides | substrates include amino acids, sugars, phosphate, CO2, and 1-carbon units from THF |
| Purine Synthesis Substrates | begins with amino acids, glycine, an amine from aspartate, two 1-carbons from THF, and two amines from glutamate |
| PRPP | source of the ribose-phosphate moiety in de novo and salvage synthesis of purines and pyrimidines |
| PRPP Synthetase | converts ribose 5-phosphate to PRPP; activated by free phosphate, inhibited by purine di- and tri-phosphate nucleotides; dependent on HMP pathway |
| PRPP-Amino Transferase | catalyzes the committed step in purine biosynthesis; transfers an amine from glutamine to make 5-Phosphoribosylamine; inhibited by AMP, GMP, and IMP |
| Allopurinolribonucleotide | drug treatment for gout that, when broken down, acts as an inhibitor for PRPP-Amino Transferase to stop the production of purines |
| IMP | the parent purine from which all other purines are made; synthesized in many steps from PRPP |
| AMP | derived from IMP and is created using an amine from aspartate, releasing fumarate; made when GTP is high |
| GMP | derived from IMP and is created using an amine from glutamine; made when ATP is high |
| Adenylate Kinase | phosphorylates AMP to make it ADP and then ATP |
| Guanylate Kinase | phosphorylated GMP to make it GDP and then GTP |
| THF | needed for purine synthesis because it provides a source of 1-carbon units |
| Poly Glu | when attached, traps compounds inside cells; works in some cancers to keep them from spreading |
| Methotrexate | folate analog that inhibits dihydrofolate reductase, limiting the amount of THF available for purine synthesis; can kill all dividing cells |
| Sulfonamides | sulfa drugs that competitively inhibit folic acid in bacteria, stopping its synthesis as well as purine synthesis |
| Trimethoprim | drug that binds much more tightly to bacterial DHFR than to mammalian DHFR, so it is useful as an antibacterial agent |
| Salvage Pathway | recycles purine bases in an energy efficient manner; uses PRPP as the source of ribose-P; important in tissues with low de novo synthesis (aka the brain) |
| Adenosine Phosphoribosyl Transferase (APRT) | salvage enzyme that makes adenine and PRPP into AMP |
| HGPRT | salvage enzyme that makes IMP from hypoxanthine and PRPP AND makes GMP from guanine and PRPP |
| Lesch-Nyhan Syndrome | X-linked recessive disorder where HGPRT is deficient, causing increased PRPP and decreased IMP and GMP, with increased purine synthesis; get excessive production of uric acid and self mutilation and involuntary movements |
| Allopurinol for Lesch-Nyhan | used as a treatment for Lesch-Nyhan and reduces the features shared with gout but not the neurological or behavioral manifestations |
| Adenosine Deaminase (ADA) Deficiency | causes abnormalities in purine metabolism that selectively kills lymphocytes, leading to severe combined immunodeficiency (SCID); have high levels of dATP; infants usually die of overwhelming infections |
| AMP Deaminase | breaks down AMP into IMP |
| Adenosine Deaminase (ADA) | breaks down adenosine to inosine |
| Muscles and AMP | aspartate and fumarate are biproducts of the buildup and breakdown of AMP, and muscles use these as their way of making TCA cycle intermediates to power their needs |
| Purine Nucleoside Phosphorylase (PNP) | converts nucleosides to bases (aka inosine to hypoxanthine and guanosine to guanine) |
| PNP Deficiency | immunodeficiency caused by the lac of this enzyme that is associated with impaired T cell function |
| Uric Acid | the end product of purine degradation; catalyzed by xanthine oxidase; excreted in the urine |
| Goat | excess of uric acid that causes excruciatingly painful joint inflammation and kidney disease |
| Primary Hyperuricemia | caused by an inborn error in uric acid metabolism; usually have normal urinary output but increased serum levels |
| Secondary Hyperuricemia | uric acid accumulation due: chronic renal insufficiency, glucose 6-phosphatsase deficiency (gives increased purine biosynthesis), or leukemia |
| Glucose 6-Phosphatase Deficiency | gives increased availability of g6-P and thus increased rate of ribose 5-P production; this increases PRPP and then stimulates purine biosynthesis |
| Allupurinol | analog of hypoxanthine that acts as a substrate and then as an inhibitor of xanthine oxidase. stopping the release of uric acid; the material allupurinol makes can then be excreted |
| Xanthine Oxidase | breaks down xanthine in the last step of purine degradation to make uric acid |
| Allopurinal and HGPRT | serves as a substrate for HGPRT and reacts with PRPP to be converted into a nucleotide, decreasing the level of PRPP and thus purine synthesis |
| Probenecid | inhibits renal tubular absorption of urate; used as a gout treatment |
| Ribonucleotide Reductase | converts ribonucleotides to deoxyribonucleotides; increases during G1/S for DNA synthesis; uses NADPH |
| Ribonucleotide Reducatase Inhibitors | inhibited by high levels of dATP as well as by hydroxyurea |
| Carbamoyl Phosphate Synthetase II | cytosolic enzyme that is the regulated step in pyrimidine synthesis; makes carbamoyl phosphatase from ATP, CO2, and Glutamine; activated by ATP and PRPP and inhibited by UTP |
| Aspartate Transcarbamoylase | replaces the phosphate group on carbamoyl phosphate with an asparatate, helping to form the pyrimidine ring structure |
| Dihydroorotase | takes carbamoyl aspartate and closes the ring using water to make dihydroorotate |
| Dihyroorolate Dehydrogenase | irreversibly oxidizes dihydroorotate to orotate in the mitochondria; makes NADH |
| UMP Synthase | multifunctional enzyme that both transfers a ribose to orotate and then decarboxylates it to make UMP |
| Orotic Aciduria | caused by the mutation of UMP synthase, resulting in megaloblastic anemia (from rapidlyy dividing marrow cells) and excretion of large amounts of orotate; fixes itself with a diet rich in uridine or cytidine |
| Agent 6-Azauridine | antineoplastic agent gives an acquired form of orotic aciduria |
| CTP Synthase | enzyme that aminates UTP, making CTP |
| UTP Synthesis | occurs from UMP; occurs by sequential actions of a nucleoside monophosphate kinase and a nucleoside diphosphate kinase |
| dCMP Deaminase | enzyme that catalyzes the deamination of dCMP to dUMP |
| dUTP Diphosphohydrolase | enzyme that removes diphosphohydrolase, removing pyrophosphate from dUTP and releasing dUMP |
| Thymidilate Synthase | catalyzes the conversion of dUMP to TMP by making a methyl transfer; uses 5,10-methylene THF to do so |
| Thymidilate Kinase | catalyzes the conversion of TMP to TDP using ATP |
| Thymidine Kinase | enzyme that catalyzes the breakdown of thymidine to TMP; elevated in growing tissues |
| Fluorouracil | blocks the synthesis of TMP; binds to thymidylate synthase in the presence of THF; die a :thymineless death" |
| Viral Infection | needs a source of nucleotides; if it occurs in non-dividing cells than the pool is low; if you use AZT, this mimics that |
| Herpes Virus | encodes for thymidine kinase, ribonucleotide reductase, and dUTPase so that it can accomodate for a low nucleotide pool |
| Acyclovir | targets thymidine kinase; gets incorporated in viral DNA so that DNA replication can no longer occur |
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