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23 Cards in this Set
- Front
- Back
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What is the difference between nucleotides and nucleosides?
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Nucleotides contain a phosphate group and nucleosides are just a ribose sugar or deoxyribose sugar plus a base.
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The small intestine breaks down nucleic acids to nucleotides and nucleosides which then breakdown into parts which travel to the ___ and break down further ___.
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Pyrimidines, purines, and pentose travel to the liver where pyrimidines break down into beta-alanine, beta-aminoisobutyrate, and CO2 + urea. Purines break into uric acid and travel to the kidney.
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PRPP is the source of ribose moiety for the synthesis of nucleosides and nucleotides. It is made from ___ and ___ and it's synthesis is inhibited by ___.
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PRPP is made from Ribose-5-Phosphate via glucose from the pentose phosphate shunt. It also requires two phosphates from ATP (note ATP to AMP). It is inhibited by pyrimidines and purines (IMP, AMP, and GMP).
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PRPP goes to 5-phosphoribosyl-1-amine via ___. It is also inhibited by ____.
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PRPP glutamyl amidotransferase. This is inhibited by IMP, AMP, and GMP (products).
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IMP is the first purine nucleotide formed and is the branch point for ___ and ___ which are made from ___ and ___ respectively.
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AMP from aspartate
GMP from glutamine Note: these feedback inhibit their production from IMP. They are phosphorylated and/or converted to deoxynucleotides to make ATP, GTP, dATP, and dGTP for RNA and DNA biosynthesis. |
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ADP/GDP goes to dADP/dGDP via what enzyme? Which requires what cofactor? What enzyme reduced the cofactor back?
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ribonucleotide reductase
thioredoxin thioredoxin reductase (using NADPH) |
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AMP can be degraded in two ways. One was deaminates AMP to IMP which is broken down into inosine. What is the other way to break down AMP to IMP?
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AMP can be dephosphorolated to adenosine which is subsequently deaminated by adenosine deaminase (ADA) releasing NH4+. ADA is a clinical correlate!!
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Adenosine deaminase deficiency (ADA).
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With ADA deficiency adenosine cannot deaminate to inosine to breakdown AMP. This causes a buildup of adenosine and deoxyadenosine which leads to severe combined immunodef. disease or SCIDs. Human gene therapy is now utilized for this.
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GMP is broken down into ____.
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Guanosine
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Inosine and Guanosine break down into ____ and ____.
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Inosine = Hypoxanthine
Guanosine = Guanine |
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Guanine and Hypoxanthine are either deaminated or oxidized respectively into ____.
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Xanthine
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Xanthine is broken down into ___ which is catalyzed by ____ and inhibited by what drug?
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Xanthine goes to Uric Acid via xanthine oxidase. It is inhibited in gout by a drug called allopurinol.
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Uric acid aka Urate breakdown into ___.
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Urine.
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Hyperuricemia (Gout).
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Excessive uric acid levels in the blood due to INCREASED purine degradation. Urate can crystallize because it's not as soluble as xanthine or hypoxanthine and causes damage to joints and kidneys. Allopurinol is used to treat gout and inhibits xanthine oxidase.
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Purine Salvage Pathway. What key enzyme?
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Hypoxanthine and guanine react with PRPP to form IMP and GMP. Enzyme = HGPRT or hypoxanthine-guanine phosphoribosyltransferase.
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HGPRT deficiency
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No purine salvage pathway. Cannot rebuild GMP and IMP which causes severe neuronal problems. Lesch-Nyhan Syndrome = mental deficiency, self-destructive behavior, and gout.
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Explain the rate limiting step of pyrimidine synthesis.
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Glutamine, CO2 and 2ATP synthesize carbamoyl phosphate via the enzyme CPS-II (carbamoyl phophate II). This is negatively regulated by UTP (downstream product) and positively regulated by PRPP. Location is cystol. Compare with CPS-I.
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Hereditary Orotic Aciduria.
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Genetic defect in orotate phophoribosyltransferase and/or orotidine decarboxylase. High levels of orotic acid excretion, anemia, and growth retardation. Treat with supplement uridine in diet (bypass bottleneck). Uridine converts to UTP which blocks CPS-II.
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Pyrimidines are broken down to ___ and ___.
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Uracil and thymine.
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Uracil and thmine breakdown to ___ and ___ respectively.
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Beta-alanine and beta-aminoisobutyrate.
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The breakdown products are ___ unlike purines.
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highly soluble and don't precipitate.
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Beta-alanine and beta-amino... are excreted in ___.
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Urine or further metabolized to CO2, H2O and NH4+.
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Reduction of the nucleoside into the deoxynucleoside occurs at the ___ level.
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diphosphate
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