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29 Cards in this Set
- Front
- Back
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Nucleotides/Functions |
-Nucleotides polymerize to make DNA and RNA -Tripolymers make Energy for cell (AMP->ATP) -Carry active intermediates in metabolic pathways such as SAM and UDP-glucose -Component of many coenzymes |
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Nucleotide Salvaging |
Nucleotides are salvaged from degradation of nucleic acids or made available through our diets. =Non hepatic tissues rely on salvage pathway |
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Nucleotide DeNovo Synthesis |
Nucleotide synthesis from scratch |
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DeNove Synthesis onset |
Biosynthesis of purine nucleotides begins with Ribose sugar must be activated by something high energy being added to it. -In this case it is pyrophosphate, and the product is PRPP via PRPP synthetase |
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Active forms of folate in purine synthesis |
N10 Formyl FH4 (C8) and (C2) |
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AMP and GMP Synthesis |
-IMP is precursor for both -AMP- Aspartate donates an amine and fumarate leaves -GMP-C2 is oxidized and O is replaced by N from glutamine |
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Regulation of DeNove Purine synthesis |
IMP biosynthesis is energetically expensive and AXP, GXP production block enzymes in pathway -PRPP synthetase is inhibited by ADP and GDP -Glutamine PRPP Amidotransferase by all 3 isoforms |
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Cross Regulation in AMP and GMP synthesis |
-AMP inhibits adenylosuccinate synthetase -GMP inhibits IMP dehydrogenase -Synthesis of AMP req. GTP -Synthesis of GMP req ATP |
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deoxyGDP and deoxyADP |
Ribonucleotide Reductase (RR) reduces the 2' hydroxyl group to make deoxy isoforms |
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Human Catabolism of Purines |
-Adenosine and Guanosine are converted to Uric Acid in humans -Adenosine is first converted to inosine via adenosine deaminase -Both pathways meet up and Xanthine Oxidase and guanine deaminase form XANTHINE -Xanthine oxidase the converts Xanthine to uric acid |
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Problem with purine catabolism |
Uric acid is in a ring structure and humans do not possess the enzyme necessary to open that ring to make more plasma-soluble -Accumulation=Gout |
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Gout |
-Overproduction or underexcretion -UE- Uric acid is generated but lactic acidosis from drinking effects on kidneys compete for excretion. Lactate is always preferred. -OP- DNA degradation in high turnover cells |
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Gout Tx |
Allopurinol- Analog of hypoxanthine and inhibits xanthine oxidase limiting uric acid. Causes build up in Hypoxanthine and Xanthine which are easier to excrete than Uric Acid |
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Purine Salvage Pathway |
Synthesis from the nucleosides that become available Non hepatic tissues use this as main form of synthesis |
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Explanation of PSP |
-After formation of IMP, AMP or GMP are made -PRPP adds phosphate group back to get ATP, GTP -Key enzyme is hypoxanthine Guanine phosphoribyl transferase (HGPRT) |
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Lesch-Nyhan Syndrome |
X linked (male dominant) genetic mutation that decreases or abolishes HGPRT activity PRPP levels increase and purines are synthesized in excess and therefore more broken down- Uric acid urinated Affected children- Mental retardation self mut. |
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ADA Deficiency |
ADA deaminase is first step that converts adenosine to inosine in degradation. No ADA, adenosine accumulation leads to SCID because of inhibition of RR via adenosine- rapidly dividing cells in bad trouble |
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Pyrimidine Synthesis |
Pyrimidine ring is formed first and then combined w/ PRPP to form initial UMP nucleotide |
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Steps involved in pyrimidine synthesis |
CPSII in cytosol catalyzes carboamoyl phosphate formation from CO2 and nitrogen/glutamine -Aspartate transcarbamoylase catalyzes formation of NCA, and dehydration/dehydrogenation makes orotate -Orotate+PRPP = UMP |
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Regulation Pyrimidine synthesis |
UTP and UDP inhibits CPSII and PRPP feeds it |
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CPSI v CPSII |
CPSI- Urea Cycle, NH4 nitrogen source, mitochondrial and activated by NAG CPSII- Pyrimidine, Glutamine nitrogen source, Cytosolic, PRPP activated and inhibited by UTP |
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CTP synthesis |
CTP synthetase makes CTP from UTP, and RR makes it dCTP |
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Methylation of Uracil |
Catalyzed by thymidylate synthase to form dTMP and dUMP dUMP converted to dTMP by receiving a methyl group from FH4 |
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Inhibition of thymidylate synthase |
5-Fluorouracil inhibits -Is a pyrimidine analog, converted to FdUMP which causes thymineless death |
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Catabolism of pyrimidines |
Pyrimidine rings can be cleaved unlike purines No intermediates can really build up because everything is very soluble |
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Orotic Aciduria |
Caused by orotate build up and UMP production screws with CPS2 and it makes orotate constantly |
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CPS I Deficiency |
-Carbamoyl phosphate not made because CPS1 not work -Hyperammonemia present -No Orotic Acid build up -Low BUN |
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OTC deficiency |
-Orotic Acid present, Hyperammonemia, and low BUN |
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CPSII deficiency |
-No hyperammonemia -Normal BUN |
