Term
| Briefly describe what is required in the formation of inosinic acid. |
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Definition
| 1) PRPP (from R5P + ATP): 2) 2 N's from glutamines ß (-) Azaserine); 3) 2 formate C's (from 10-formyl THF ß (-) Sulfonamide); 4) N-C=C from Glycine; 5) N from Aspartate. |
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Term
| Why aren't many purines synthesized de novo? |
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Definition
| Cost of making IMP is very expensive and it's a crazy long pathway. 90% of nucleotides come from salvage pathways. |
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Term
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Definition
| 1) de novo: IMP + Asp à ATP + Fum (uses GTP); 2) Salvage: a) Adenine + PRPP à AMP + PPi (APRT), b) Adenosine + ATP à AMP + ADP (Nucleoside kinase-only adenosine in humans and not widely used) |
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Term
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Definition
| 1) de novo: IMP + H2O + Gln à GMP + Glu (uses NAD+ and ATP); 2) Salvage: Guanine + PRPP à GMP + PPi (HGPRT (gout, lech-nyon)); 3) ADP + GDP à ATP + GMP (Nucleoside monophosphate kinase) |
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Term
| Briefly describe how UDP and CTP are formed. |
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Definition
| Carbamoyl phosphate (from CPSII using Gln + CO2) + Asp + PRPP à UMP (5 step RXN by one big enzyme). UMP à UDP (ATP) à UTP (ATP) à CTP (ATP, GlnàGlu). This is part of keeping balance in the pool. |
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Term
| True or false: Most cells don't make deoxyribonucleotides at any one time. |
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Definition
| True. Only dividing cells and cells carrying out DNA damage response make them. |
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Term
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Definition
| UDP à dUDP (reductase) à dUTP (rare) à dUMP à dTMP (thymidylate synthase with 5,10-methylene THFàDHF) à dTTP (2 ATP) |
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Term
| What does hydroxyurea do? |
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Definition
| It blocks the action of reductase so that deoxyribonucleotides aren't synthesized. (Feedback inhibition does this too.) |
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Term
| True or false: There are two salvage pathways for thymine deoxyribonucleotides. |
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Definition
| True: 1) Thymine + dR1P à Thymidine + Pi; 2) Thymidine + ATP à dTMP + ADP |
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Term
| True or false: 5-Fluorouracil is an anticancer agent that prevents DHF from reconverting to THF? |
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Definition
| False. That's what methotrexate, the folic acid analog, does. 5-Fluorouracil prevents the conversion of dUMP to dTMP by forming F-dUMP, binding 5,10-methylene THF/thamidylate synthase, and permanently inhibiting thamidylate synthase. Both methotrexate and 5-Fluorouracil should be administered at just sub-lethal doses. |
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Term
| Name two types of enzymes that are involved in the degradation of purine and pyramidine nucleotides. |
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Definition
| 1) Nucleotidases (remove phosphates). 2) Nucleoside phosphorylases (add phosphate then cleave both phosphate and ribose). |
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Term
| True or false: All purines are eventually degraded to uric acid by way of Xanthine. |
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Definition
| True. Xanthine oxidase catalyzes this RXN. |
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Term
| True or false: All pyrimidines are eventually degraded to B-Aminoisobutyric Acid by way of Thymine. |
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Definition
| False: B-Aminoisobutyric Acid through Thymine is one way. The other is B-Alanine through Uracil. |
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Term
| True or false: Reductase converts purines and pyrimidines to their deoxyribose forms when they are DP's. |
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Definition
| True for A, G, C, U. Thymidine works through Uracil (UDP à dUDP à dUMP à dTMP (5,10-methylene THF) à dTTP |
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Term
| What do B-Alanine and B-Aminoisobutyric Acid form when transaminated? |
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Definition
| B-Alanine forms Malonyl CoA and B-Aminoisobutyric Acid forms Methyl Malonyl CoA. Malonyl CoA is also a product of FA synthesis (from acetyl CoA (C4)) and an inhibitor of carnitine palmitoyl transferase (C17). |
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Term
| What's the deal with hypoxanthine? |
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Definition
| It's involved in purine degradation and salvaging. Degradation: AMP à Adenosine à Inosine à Hypoxanthine (-R1P) à Xanthine (extra -OH by Xanthine Oxidase, generation of superoxide) à Uric Acid (again: extra -OH by way of Xanthing oxidase, generation of superoxide) |
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Term
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Definition
| Elevated uric acid levels because purines are being over-produced. Can be caused by PRPP synthetase not responding to feedback inhibition by purine nucleoside diphosphatases or by deficiency of HGPRT leading to increased PRPP activity. Rx = Allopurinol (blocks production of uric acid). |
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Term
| What's Lesch-Nyhan Syndrom? |
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Definition
| Complete HGPRT activity deficiency so hyoxanthine and guanine are not salvaged. Rx = allopurinol to stop uric acid production; however this doesn't help neurological symptoms, which remain largely unexplained. X-linked. |
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Term
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Definition
| ADA = Adenosine Deaminase. Conversion to deoxyinositine and inositine isn't happening. White blood cells can't proliferate. Associated with Severe Combined Immunodeficiency (SCID). Tx = bone marrow transplant. |
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