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Blake_Biochemistry Test II > Blake_Biochem_20-21_Nucleotides > Flashcards

Blake_Biochem_20-21_Nucleotides Flashcards

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1
Q

Nucleotides

A

Phosphate esters of nucleosides

Containe a base, a sugar, and a phosphate

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2
Q

Heirarchy of Nucleic acids

A
  • Nucleic acids (polynucleotides)
    • Covalently-Bonded Nucleotides
    • H-Bond bind complementary Nucleic Acids
  • Nucleotides (base - sugar - phosphate)
    • Nucleosides
    • Phosphoric Acid
  • Nucleosides
    • Bases (purines and pyrimidines)
    • Sugars (ribose and deoxyribose
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3
Q

Nucleosides

A

a base (purine or pyrimidine) with a sugar (ribose or deoxyribose) with NO phosphate

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4
Q

List the Purine bases

A

Adenine*

Guanine*

Hypoxanthine

Xanthine

*involved in genetic code

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5
Q

List the pyrimidine bases

A

Cytosine

Uracil

Thymine

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6
Q

Nucleoside of Hypoxanthine

A

Inosine

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7
Q

How are nucleosides abreviated?

A

Prefix+sine

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8
Q

How are nucleotides abbreviated?

A

Nucleoside monoposphate

eg Inosine -> IMP

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9
Q

how are ribose nucleotides converted to deoxynucleotides?

A

ribonucleotide reductase

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10
Q

what else is required for reduction of ribose by rionucleotide reductase?

A

NADPH

(ATP stimulates)

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11
Q

what inhibits ribonucleotide reductase?

A

dATP

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12
Q

How are sugars (ribose or deoxyribose) attached to bases?

A

N-glycosidic bond

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13
Q

what kinds of bonds attach the first phosphate to the ribose-sugar in a nucleotide?

A

Phosphoric acid ester bonds

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14
Q

what kind of bonds link the 2nd and 3rd phosphates to a nucleotide?

A

Phosphoric acid anhydride bonds

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15
Q

Hydrolysis Energies:

ATP⇒ADP+Pi

ATP⇒AMP+PPi

PPi⇒Pi+Pi

A
  • ATP⇒ADP+Pi (Delta G= -7.3 kcal/mol)
  • ATP⇒ AMP+PPi (DeltaG= -10.9 kcal/mol)
  • PPi ⇒Pi+Pi (DeltaG= -4.0kcal/mol)
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16
Q

How many base pairs per turn of the double helix?

How long is the spacing of one nucleotide pair?

A

10

3.4Å

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17
Q

What is the rate limiting nucleotide in DNA synthesis?

Why?

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A

Thymine

The fact that TTP is almost never synthesized and only dTTP is generated, unlike the other 3. The other 3 are synthesized at a higher concentration because they can be incorporated into RNA and readily available to be reduced to dNTPs for DNA when needed. So, the concentration of dTTP have to reach a level equal to the other dNTPs before DNA synthesis can begin.

18
Q

How is DNA/RNA digested?

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A
  • ribonucleases (RNA); deoxyribonucleases (DNA) separate chains of double helix to leave short oligomers
  • Phosphodiesterase seperates nucleic acids to form Nucleotides (NMP or dNMP)
  • Nucleotidase cleaves phosphate groups to form Nucleosides
  • Nucleosidase cuts N-glycosidic bonds to cleave base and ribose-sugars
19
Q

ADA

Study These Flashcards
A

Adenosine Deaminase

Plays an important role in adenosine homeostasis and modulates signaling by extracellular adensosine and so contributes indirectly to signaling

20
Q

Overproduction of ADA

Study These Flashcards
A

Causes hemolytic anemia (rare). Increased degradatioin of adenosine depletes adenine nucleotide pool and triggers premature destruction of RBCs

21
Q

Underproduction of ADA

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A

associated with the second most comon form of severe combined immunodeficiency (SCID)

22
Q

Xanthine Oxidase

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A
  • Catalyzes the oxidation of hypoxanthine to xanthine AND xanthine to Uric acid
  • Has 2 Flavin adenine dinucleotides (FADs), 2 Mo atoms, and 8 Fe atoms per moledule of enzyme
  • Drug target for Allopurinol in the treatment of Gout
23
Q

GOUT

  • How is gout identified?
  • What are the two types?
  • Why is gout painful?
  • What are preventable causes?
  • What is the standard treatment?
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A
  • high levels of uric acid in the blood
  • Primary hyperuricemia (over production of UA); Secondary hyperuricemia (under-extretion of UA)
  • Sodium Urate precipitate; Phagocytic cells release factors that innitiate and acute inflammatory response
  • Diet: purines: beans, meat, seafood, alchohol
  • colchicine (deceases movement of granulocytes to affected area); Allopurinol (inhibits xanthine oxidase)
24
Q

GOUT

  • What is the normal serum U.A. level?
  • Urinaty U.A.?
Study These Flashcards
A
  • adult males: 4-8.6mg/dL
  • adult females: 3-5.9mg/dL
  • <750mg/24hr
25
**Pyrimidine** Nucleotide Catabolism: UTP ptwy: Substrate/Enzyme
* (d)**UTP**/nucleotidase * ⇒**Uridine** or (DeoxyU)/Uridine phosphorylase * ⇒**Uracil** + ribose 1-P (or 2-deoxyribose 1-P) * ⇒**ß-alanine** * ⇒**Malonyl CoA** (ketogenic)
26
**Pyrimidine** Nucleotide Catabolism: Substrates/Enzymes:
* **dTTP to Deoxythymidine/**nucleotidase * **Deoxythymidine to Thymine**/Uridine phosphorylase * ⇒**Thymine +** 2-deoxyribose 1-P * ⇒**ß-aminoisobutyrate** * ⇒**Methylmalonyl CoA** (glucogenic) +**Succinyl CoA** (glucogenic)
27
Purine Nucleotide Catabolism: GMP ptwy substrate/Enzyme
* **GM​P**/nucleotidase * **Guanosine**/PNP (purine nucleoside phosphorylase * **Guanine** +Ribose 1-P/Guanine deaminase * **Xanthine**/Xanthine oxidase * **Uric Acid**
28
**Pyrimidine** Nucleotide Catabolism: CTP ptwy: Substrate/Enzyme:
* (d)**CTP**/nucleotidase * ⇒**Cytosine** (deoxyC)/ aminohyrolase * ⇒**Uridine** or **Deoxyuridine**/Uridine phosphorylase * ⇒**Uracil** + ribose 1-P (or 2-deoxyribose 1-P) * ⇒**ß-alanine** * ⇒**Malonyl CoA** (ketogenic)
29
**Purine** Nucleotide Catabolism: Adenosine Ptwy Substrate/Enzyme
* **AMP**/nucleotidase * **Adenosine**/Adenosine Deaminase (ADA) * **Inosine/**Purine Nucleoside Phosphorylase (PNP) * **Hypozanthine** + Ribose 1-P/ Xanthine Oxidase * **Xanthine**/ Xanthine Oxidase * **Uric Acid**
30
**Purine** Nucleotide Catabolism IMP ptwy Enzyme/Substrate
* **AMP**/ AMP deaminase * **IMP** + Phosphate * **Inosine**/ PNP * **Hypoxanthine**/ Xanthine Oxidase * **Xanthine**/ Xanthine Oxidase * **Uric Acid**
31
Phase I-III: Purine Synthesis: * Substrate to Products/Enzyme * **+**/**-** * byproducts or additional substrate
* I. **a-D-ribose 5P to PRPP**/PRPP synthease * **+**Pi/ **-** Purine Nucleotides (GMP, AMP, IMP) * ATP⇒AMP * II: **PRPP to PRA**/glutamine PRPP Amidotransferase * **+** PRPP/ **-** Purine Nucleotides (GMP, AMP, IMP) * Gln⇒Glu, ⇒PPi * III: **PRA to IMP/** 9 rxns (tetrahydrofolate: N10-fTHF) * **-** Methotrexate * **​**CO2, Gly, Gln, Asp, N10-fTHF (additional substrates)
32
Methotrexate
* Antineoplastic agent * **inhibits DNA** replication/synthesis * **Binds dihydrofolate** reductase 100x more tightly
33
Phase IV Purine Synthesis: GMP ptwy * Substrate to Products/Enzyme * +/- * Byproducts or additional substrates
* **IMP** to **XMP** (xanthosine phosphate)/ IMP dehyrogenase * - GMP * NAD+ ⇒ NADH * **XMP to GMP**/ GMP synthase * Gln ⇒Glu, ATP⇒AMP +PPi * **GMP to GDP/ 2 paths** 1. **​GDP to dGDP/**ribonucleotide reductase * dGDP to dGTP 2. **GDP to GTP**
34
Phase IV Purine Synthesis: AMP ptwy * Substrate to Products/Enzyme * +/- * Byproducts or additional substrates
* **IMP to adenlylosuccinate MP/** adenylosuccinate synthease * -AMP * Asp ⇒, GTP⇒GDP * **Adenylosuccinate MP to AMP** * **​**⇒Fumarate (used in TCA) * **AMP to ADP**/2 paths 1. **ADP to dADP**/ribonucleotide reductase * ​dADP to dATP 2. ​**ADP to ATP**
35
Phase I Pyrimidine Synthesis: 4 steps * Substrate to Products/Enzyme * +/- * Byproducts or additional substrates
* **Gln to Carbamoylphosphate**/Carbaboyl Phosphate Synthease II * +PRPP/-UTP * ⇒Glu, 2ATP⇒2ADP, HCO3-(in), Pi (out) * **Carbanoylphosphate to Carbamoyl Aspartate**/ Aspartate transcarbomylase * Asp(in), Pi (out) * **Carbamoyl Aspartate to Dihydroorotate**/ dihydroorotase * ​H2O (out) * **Dyhydroorotate to Orotate**/ dyhydroorotate dehydrogenase
36
Phase II Pyrimidine Synthesis: 2 steps * Substrate to Products/Enzyme * +/- * Byproducts or additional substrates
* **Orotate to OMP**/ UMP synthase * PRPP (in), PPi (out) * **OMP to UMP**/ UMP synthase * H2O (in), HCO3- (out)
37
Phase III Pyrimidine Synthesis: dTTP 5steps * Substrate to Products/Enzyme * +/- * Byproducts or additional substrates
* **UMP to UDP**/ Phosphorylase * Pi (in) * **UDP to dUDP**/ ribonucleotide reductase * H2O (out) * **dUDP to dUMP**/ UTP kinase * dUDP to dUTP to dUMP/ dUTPase * **dUMP to dTMP**/Thymidylate synthase * N5,N10-mTHF⇒Dihydrofolate * dTMP to dTDP to dTTP
38
Phase III Pyrimidine Synthesis dCTP 5steps * Substrate to Products/Enzyme
* **UMP to UDP**/ ? phosphorylase * **UDP to UTP**/ ? phosphorylase * **UTP to CTP**/ *CTP synthase* * **CTP to CDP**/ ? kinase * **CDP to dCDP**/ *ribonucleotidase reductase* * dCDP to dCTP/ ? phosphorylase
39
Purine Nucleotide Salvage Pathway
* **Adenine to AMP**/ Adenine Phosphoribosyl Transferase (APRT) * PRPP to PPi * **Guanine** (or Hypoxanthine) to **GMP** (or IMP)/ Hypoxanthine-guanine phophorybosyl-transferase (HGPRT) * PRPP to PPi
40
Pyrimidine Nucleotide Salvage Pathway
* Uracil * **Uracil to Uridine**/ Uridine phosphorylase * Ribose 1-P to Pi * ​**Uridine to UMP**/ Kinase * **UMP to UDP to UTP**/ Phoshphorylase * Thymine * **Thymine to Deoxythymidine**/ thymidine phosphorylase * 2-deoxyribose 1-P to Pi * **Deoxythymidine to dTMP**/ thymidine kinase * **dTMP to dTDP to dTTP/** Phosphorylase

Blake_Biochemistry Test II (11 decks)

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