Metabolism of purines and pyrimidines - exercise -

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Metabolism of purines and pyrimidines- exercise -

• Vladimíra Kvasnicová

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Purine nucleotides

1. include an aromatic cycle in the structure
2. can contain either adenine or thymine
3. include N-glycosidic bond
4. are composed of a nucleoside bound to phosphoric
   acid by an anhydride bond

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Purine nucleotides

1. include an aromatic cycle in the structure
2. can contain either adenine or thymine
3. include N-glycosidic bond
4. are composed of a nucleoside bound to phosphoric
   acid by an anhydride bond

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PURINE BASES
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
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ribonucleoside deoxyribonucleoside
N-glycosidic bond
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
6
ribonucleotide deoxyribonucleotide
ester bond
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
7
Pyrimidine nucleotides

1. include an imidazol ring in the structure
2. include thymidine- and cytidine monophosphate
3. contain an ester bond
4. can include 3 phosphate groups in their structure

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Pyrimidine nucleotides

1. include an imidazol ring in the structure
2. include thymidine- and cytidine monophosphate
3. contain an ester bond
4. can include 3 phosphate groups in their structure

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PYRIMIDINE BASES
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
10
ribonucleosides deoxyribonucleoside
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
11
Ribonucleotides N-glycosidic bond ester
bond anhydride bond
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
12
Purine and pyrimidine nucleotides can be used

1. as nucleoside triphosphates for nucleic acid
   synthesis
2. in energetic metabolism of cells
3. for activation of metabolic intermediates of
   saccharides and lipids
4. in enzymatic reactions some coenzymes are
   nucleotides

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Purine and pyrimidine nucleotides can be used

1. as nucleoside triphosphates for nucleic acid
   synthesis
2. in energetic metabolism of cells
3. for activation of metabolic intermediates of
   saccharides and lipids
4. in enzymatic reactions some coenzymes are
   nucleotides

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Synthesis of nucleotides

1. uses products of pentose cycle
2. includes phosphoribosyl diphosphate (PRDP PRPP)
   as a substrate
3. needs derivatives of folic acid
4. proceeds in a cytoplasm only

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Synthesis of nucleotides

1. uses products of pentose cycle
2. includes phosphoribosyl diphosphate (PRDP PRPP)
   as a substrate
3. needs derivatives of folic acid H4 folate (THF)
4. proceeds in a cytoplasm only

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• pentose cycle

PRPP PRDP
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
17
Synthesis of purine nucleotides

1. uses ammonia as a nitrogen donor
2. proceeds in a cytoplasm
3. can start from nucleosides produced by
   degradation of nucleic acids
4. includes uric acid as an intermediate

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Synthesis of purine nucleotides

1. uses ammonia as a nitrogen donor
2. proceeds in a cytoplasm
3. can start from nucleosides produced by
   degradation of nucleic acids
4. includes uric acid as an intermediateuric acid
   is the end product of purine ring degradation

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Synthesis of purine nucleotides
CYTOPLASM
Obrázek prevzat z http//web.indstate.edu/thcme/mw
king/nucleotide-metabolism.html (leden 2007)
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IMP
AMP
GMP
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
21
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
22
Synthesis of pyrimidine nucleotides

1. starts by the reaction PRDP glutamine
2. proceeds only in a cytoplasm of cells
3. includes orotic acid as an intermediate
4. includes inosine monophosphate as an intermediate

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Synthesis of pyrimidine nucleotides

1. starts by the reaction PRDP glutamine
2. proceeds only in a cytoplasm of cells
3. includes orotic acid as an intermediate
4. includes inosine monophosphate as an intermediate

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Synthesis of pyrimidine nucleotides
CYTOPLASM
mitochondrion
Obrázek prevzat z http//web.indstate.edu/thcme/mw
king/nucleotide-metabolism.html (leden 2007)
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Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
26
Synthesis of 2-deoxyribonucleotides
enzyme ribonucleotide reductase
small protein thioredoxin
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
27
Synthesis of thymidine monophosphate
Obrázek je prevzat z ucebnice Devlin, T. M.
(editor) Textbook of Biochemistry with Clinical
Correlations, 4th ed. Wiley-Liss, Inc., New York,
1997. ISBN 0-471-15451-2
28
In a regulation of nucleotide synthesis
participate

1. 5-phosphoribosyl-1-diphosphate (PRDP)
2. feed back inhibition
3. enzyme carbamoyl phosphate synthetase
   II(synthesis of pyrimidines)
4. enzyme xanthine oxidase(synthesis of purines)

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In a regulation of nucleotide synthesis
participate

1. 5-phosphoribosyl-1-diphosphate (PRDP)
2. feed back inhibition
3. enzyme carbamoyl phosphate synthetase
   II(synthesis of pyrimidines)
4. enzyme xanthine oxidase(synthesis of purines)
   enzyme of purine degradation

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Regulation of nucleotide synthesis
regulatory enzyme activation inhibition
glutamine-PRPP amidotransferase (purines) PRPP IMP, GMP, AMP (allosteric inhibition)
carbamoylphosphatesynthetase II cytosolic (pyrimidines) PRPP ATP UTP
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In a degradation of purine nucleotides

1. ammonia is released
2. CO2 is produced
3. the enzyme xanthine oxidase participates
4. uric acid is produced as the end product

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In a degradation of purine nucleotides

1. ammonia is released
2. CO2 is produced
3. the enzyme xanthine oxidase participates
4. uric acid is produced as the end product

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Degradation of purines
uric acid
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In a degradation of pyrimidine nucleotides

1. ?-amino acids are produced
2. the enzyme xanthine oxidase participates
3. orotic acid is formed
4. ammonia is produced

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In a degradation of pyrimidine nucleotides

1. ?-amino acids are produced
2. the enzyme xanthine oxidase participates
3. orotic acid is formed
4. ammonia is produced

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Degradation of pyrimidines
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Principal differences between metabolism of
purines and pyrimidines
purines pyrimidines
formation of N-glycosidic bond in 1st step of their biosynthesis (PRDP is the 1st substrate) a heterocyclic ring is formed first, then it reacts with PRDP
location of biosynthesis cytoplasm cytoplasm 1 enzymeis in a mitochondrion
products of degradation uric acid (poor solubility in H2O), NH3 CO2, NH3, ?-AMK (soluble in H2O)