Biochemistry - Lecture 5 - Nucleotide Metabolism

Front 1

What makes up a Nucleotide?

Back 1

-Nitrogenous Base
-Pentose Monosaccharide
-Phosphate Groups (1,2, or 3)

Front 2

Describe the Composition of Purines.

Back 2

2 Rings Fused Together
-5-Membered Ring
-6-Membered Ring

Front 3

Describe the Composition of Pyrimidines.

Back 3

Single, 6 Membered Ring

Front 4

Which Nucleotides are Purines?

Back 4

Pure As Gold
-Adenine
-Guanine

Front 5

Which Nucleotides are Pyrimidines?

Back 5

CUT they Py
-Cytosine
-Thymine (Uracil in RNA)

Front 6

What is a Nucleoside? How is this different from a Nucleotide?

Back 6

-Base + Pentose
-Nucleoside = Nucleotide - Phosphate Groups

Front 7

What types of Pentose Sugars are usually found attached to Nucleotides and Nucleosides?

Back 7

-Ribose
-2-Deoxyribose

Front 8

What type of Bond forms when a Nucleoside binds with Phosphate? What does this result in?

Back 8

-Ester
-Nucleotide

Front 9

How, in general (very), are purines synthesized?

Back 9

Series of Reactions that add Carbon and Nitrogen to Ribose 5-Phosphate

Front 10

What is PRPP? What role does it play in Purine Synthesis?

Back 10

-5-Phosphoribosyl-1-Pyrophosphate
-Synthesized in the 1st step of Purine Synthesis

Front 11

How PRPP synthesized?

Back 11

-Ribose 5-Phosphate is Phosphorylated with 2 Phosphates
-ATP donates the Phosphates
-Results in PRPP
-Catalyzed by PRPP Synthetase

Front 12

Which Enzyme catalyzes the Formation of PRPP?

Back 12

PRPP Synthetase

Front 13

What is the 1st step in the Synthesis of Purines? Describe this step.

Back 13

Formation of PRPP
-Ribose 5-Phosphate is Phosphorylated with 2 Phosphates
-ATP donates the Phosphates
-Results in PRPP
-Catalyzed by PRPP Synthetase

Front 14

What Activates PRPP Formation? Inhibits?

Back 14

-Activators – Phosphate
-Inhibitors – Purine Ribonucleotides (Negative Feedback)

Front 15

What is IMP? How is it formed? When?

Back 15

-Inosine Monophosphate
-5'Phosphoribosylamine + 4 ATP > IMP
-3rd Step in the Synthesis of Purines

Front 16

Which step of Purine Synthesis do PABA Analogs act? What do they do?

Back 16

Inhibitors of Purine Synthesis
-PABA Analogs - Slow down formation of THF (In Bacteria, Coenzyme for many reactions)
-Folic Acid Analogs (Methotrexate) - Inhibit Reduction of DHF to THF

Front 17

What catalyzes the formation of IMP?

Back 17

THF

Front 18

What do Folic Acid Analogs do to Purine Synthesis? What effect do they have on all Cells? What are they used to Treat?

Back 18

-Inhibit Reduction of DHF to THF, which is used as a cofactor in many reactions
-Toxic to All Dividing Cells (especially fast dividing)
-Used to Treat Cancer

Front 19

What is IMP converted to before we can make Nucleoside Di and Triphosphates?

Back 19

AMP and GMP

Front 20

What role do AMP and GMP play in Purine Synthesis?

Back 20

Formed from IMP before Nucleosides can be formed

Front 21

What inhibits the formation of AMP and GMP

Back 21

The Product!!!! - AMP and GMP

Front 22

What the fuck is so cool about Mycophenolic Acid?

Back 22

Nothing (Another flashcard later/earlier)

Front 23

What the fuck is so cool about Mycophenolic Acid?

Back 23

-Reversible Uncompetitive Inhibitor of IMP Dehydrogenase
-Prevents Formation of GMP

Front 24

What acts on IMP Dehydrogenase to prevent formation of GMP?

Back 24

Mycophenolic Acid

Front 25

What is Lesch-Nyhan Syndrome? How does it occur?

Back 25

-Deficiency of HGPRTase which catalyzes formation of Guanine
-Results in Increased PRPP, Less IMP and GMP, Increased De Novo Synthesis of Purines
-Excess Production of Uric Acid

Front 26

What is the Salvage Pathway's purpose?

Back 26

What do you think?
To salvage Nucleotides

Front 27

What is disease is deficiency of HGPRTase associated with? What does it normally do?

Back 27

-Lesch-Nyhan Syndrome
-Deficiency of HGPRTase - Catalyzes formation of Guanine

Front 28

What do we see an increase of if Lesch Nyhan Syndrome? Why?

Back 28

-PRPP
-Deficiency of HGPRTase - Catalyzes formation of Guanine

Front 29

Excessive Production of Uric Acid is a feature in what disease?

Back 29

Lesch-Nyhan Syndrome

Front 30

How are Deoxyribonucleotides Synthesized? What is this Catalyzed by?

Back 30

-Basically we just remove a Hydroxyl Group from the Oxy Form
-Ribonucleotide Reductase and Thioredoxin Reductase

Front 31

Were are Nucleic Acids Degraded? What do they form?

Back 31

-Small Intestine
-Uric Acid

Front 32

What enzyme is responsible for the Breakdown of Purines in the pathway that will ultimately go to Uric Acid?

Back 32

Purine Nucleoside Phosphorylase

Front 33

What does Purine Nucleoside Phosphorylase do?

Back 33

Breaks down Purines to Products that will go to Uric Acid

Front 34

What happens if a patient has a Deficiency of Purine Nucleoside Phosphorylase?

Back 34

-Can't get to Hypoxanthine or Xanthine
-Excess Inosine and Guanin
-Can't Produce Uric Acid

Front 35

What does Adenosine Deaminase (ADA) do?

Back 35

Convert Adenosine to Inosine

Front 36

What enzyme converts Adenosine to Inosine?

Back 36

Adenosine Deaminase (ADA)

Front 37

What type of Cells usually have the highest activity of ADA?

Back 37

Lymphocytes

Front 38

What happens if a patient has a Deficiency of ADA?

Back 38

-Accumulation of Adenosine (Can't be converted to Inosine)
-Increased dATP Levels due to Adenosine Shunting
-Inhibits Ribonucleotide Reductase
-DNA Synthesis is Inhibited

Front 39

What effects does ADA Deficiency have on the Immune System? Why?

Back 39

-DNA Synthesis is impaired
-Impairment of DNA Repair
-Leads to Accumulation of DNA Breaks in the Cell Genome
-Eventually Triggers Apoptosis of T and B Cells

Front 40

What are some ways to Treat ADA Deficiency?

Back 40

-Bone Marrow or Stem Cell Transplants
-Injection of ADA
-Gene Therapy

Front 41

What is Gout? Why does it result?

Back 41

-High levels of Uric Acid in the Blood
-Due to Underexcretion or Overproduction

Front 42

If a patient has Sodium Urate Crystals in their Kidney and/or Joints, what should you suspect?

Back 42

Gout

Front 43

What causes Gout?

Back 43

-Mutation in PRPP Synthetase Gene
-Defect in Purine Salvage Pathways
-Alcohol

Front 44

How do Mutations in PRPP Synthetase Genes result in Gout?

Back 44

-Results from Enzyme Resistance to Feedback from Purines
-Higher PRPP Levels
-Leads to Increased Synthesis of Purines
-High Levels of Uric Acid

Front 45

How do Defects in Purine Salvage Pathways result in Gout?

Back 45

-Deficiency of HGPRTase
-Accumulation of Uric Acid

Front 46

What are some symptoms of Lesch-Nyhan Syndrome?

Back 46

-Neurological Features
-Self-Mutilation
-Involuntary Movements

Front 47

What drugs are used to treat Gout?

Back 47

-Colchicine
-Allopurinol
-Probenecid and Sulfinpyrazone

Front 48

How are Pyrimidines Synthesized? How is this different from Purine Synthesis?

Back 48

-Synthesized before Addition of Ribose-5-Phosphate
-Not built upon it after Ribose-5-Phosphate Addition as for Purines

Front 49

What are the 3 Steps in Pyrimidine Synthesis?

Back 49

-1 - Synthesis of Carbamoyl Phosphate
-2 - Synthesis of Orotic Acid
-3 - Formation of Pyrimidine Nucleotide

Front 50

What is the Committed Step in Pyrimidine Synthesis? What is it Catalyzed by?

Back 50

-Synthesis of Carbamoyl Phosphate
-CPS II - Carbamoyl Phosphate Synthetase II

Front 51

What enzyme catalyzes the formation of Carbamoyl Phosphate?

Back 51

CPSII (Carbamoyl Phosphate Synthetase II)

Front 52

What is Orotic Aciduria? How does it result?

Back 52

-Deficiency in the Combination Enzyme that Metabolizes Orotate
-UMP Synthase is Deficient
-Results in Accumulation of Orotic in the Urine

Front 53

What happens if a patient is deficient in the enzyme UMP Synthase

Back 53

-Orotic Aciduria
-UMP is a Combination Enzyme that Metabolizes Orotate to Uric Acid
-Results in Accumulation of Orotic in the Urine

Front 54

How is dUMP converted to dTMP?

Back 54

Thymidylate Synthase

Front 55

What inhibits Thymidylate Synthase? What is this used to treat?

Back 55

-5-Fluorouracil
-Inhibits Tumor Growth