Moyzis1-Nucleic acids

Question 1

How much do we use amino acids every day?

Answer 1

• 400g for protein synthesis
• 30g for other molecules (purine, pyrimidines, creatine, amines, NO, glutathione, porphyrins-heme

Question 2

What are the differences between cytosine, uracyl, and thymidine?

Answer 2

Question 3

What are the two purines?

Answer 3

Question 4

What is a nucleoside, and how they numbered?

Answer 4

Nitrogenous base and a pentose monosaccharide

Ex. adenosine, deoxythymidine

Question 5

What are nucleotides?

Answer 5

• Mono-, di-, tri-phosphate esters of nucleosides
• 1P (NMP, AMP, GMP)
• 2P (NDP, ADP, GDP)
• 3P (NTP, ATP, GTP)
• First phosphate is attached by an ester linkage to the 5’-OH of the pentose

Question 6

How are purine nucleotides synthesized?

Answer 6

-The atoms of the purine ring are contributed by: CO2, formate, aspartic acid, glycine, & glutamine.

Question 7

What are the steps of purine synthesis?

Answer 7

1) Synthesis of PRPP by PRPP synthetase
2) Sequential addition of components: PRP + glutamine –> 5’-phosphoribosylamine (commited step) –> IMP
3) IMP –(GTP)–> **AMP, ** IMP—(ATP)—-> GMP
4) Conversion of nucleoside mono-P–> di-P –> tri-phosphates w/ nucleoside monophosphate kinases.

*Adenylate kinase: maintains equilibrium among AMP, ADP, & ATP

*NDPs & NTPs are interconverted by nucleoside diphosphate kinase (broad specificity)

Question 8

How do sulfonamides work?

Answer 8

• Inhibit the growth of rapidly dividing organisms by blocking synthesis of folic acid by dyhydrofolate reductase
• Folic acid’s derivative THF is a coenzyme required for purine synthesis
• Humans cannot synthesize folic acid

Question 9

How does methotrexate work?

Answer 9

• Structural analog of folic acid & inhibitor of dyhydrofolate reductase & thus thymidine synthesis
• Used to control the spread of cancer
• Interfers w/ nt synthesis of any rapidly dividing cell (bone marrow, GI tract, etc)

Question 10

What is Mycophenolic acid (MPA)?

Answer 10

• Reversible inhibitor of IMP dehydrogenase
• Usedto prevent graft rejection bc rapidly proliferating cells (B & T-cells) are deprived of a key component of nucleic acids

Question 11

What are some basic characteristics of pyrimidine synthesis?

Answer 11

• Unlike purines, pyrimidine ring is synthesized before being attached to ribose-5-P
• The source of atoms are glutamine, CO2, aspartic acid.

Question 12

What are the steps of pyrimidines synthesis?

Answer 12

1) Synthesis of carbamoyl phosphate (regulated step)
2) Formation of carbamoyl aspartate
3) Ring closure to dihydroorotate
4) Oxidation to produce orotate (orotic acid)
5) Ring is converted to OMP, using PRP
6) Conversion to UMP w/ OMP carboxylase

Question 13

What is orotic aciduria?

Answer 13

• Rare genetic defect caused by a deficiency of the last 2 steps in the pyrimidine synthesis, results in orotic acid in the urine.
• Diet rich in uridine results in partial improvement.

Question 14

What is ribonucleotide reductase?

Answer 14

• Enzyme that converts ribonucleotide diphosphates (UDP) into 2’-deoxyribonucleotides (dUDP)
• Uses THF, which donated 2 hydrogens and 1 carbon
• Activated by ATP, inactivated by dATP

Question 15

What is 5-FU?

Answer 15

• Anti tumor agent that works by inhibiting thymidilate synthetase. It is converted to 5-FdUMP, which binds permanently to the inactivated enzyme. “Suicide” inhibitor.

Question 16

What is gout?

Answer 16

• Type of arthritis. It occurs when uric acid (Needle-shaped crystals of sodium urate) builds up in blood and causes inflammation in the joints and tissues.
• Treatment with allopurinol results in an accumulation of more soluble hypoxanthine and xanthine
• Should consume only modest amounts of foods high in nucleic acids

Question 17

What is Adenine deaminase (ADA) deficiency?

Answer 17

• Results in increased dATP and inhibition of DNA synthesis
• Lymphocytes have the highest ADA activity, so T and B cells cannot replicate(SCID)
• The first genetic disease successfully treated by gene therapy.

Question 18

How is Uric acid formed?

Answer 18

1) amino group removed from AMP gives IMP
2) IMP & GMP converted to inosine & guanosine
3) converted to bases: guanine & hypoxanthine
4) Guanine delaminated to Xanthine, Hypoxanthine oxidized to Xanthine
5) Xanthine oxidized to Uric acid

Question 19

What are allopurinol and uloric?

Answer 19

Drugs used to treat gout. Inhibit Xanthine oxidase, which results in an accumulation of more soluable hypoxanthine and xanthine instead of Uric acid.

Question 20

What is Lesch-Nyhan syndrome?

Answer 20

• X-chromosome linked recessive disorder
• complete deficiency of HPRT
• Inability to salvage hypoxanthine or guanine results in excessive uric acid.
• Increased PRPP, & decreased IMP & GMP. cause de novo purine synthesis increase
• Severe heritable form of gout. Patients produce urate kidney stones & have neurological features (self-mutilation & involuntary movements)

Question 21

What are catecholamines?

Answer 21

• Dopamine(nt), NE, and epinephrine-adrenalin
• Biologically active amines
• Outside the nervous system, NE & epinephrine regulate carbohydrate & lipid metabolism
• Released from storage vesicles in the adrenal medulla in response to fright, exercise, cold & low glucose levels
• They increase the degradation of glycogen and increase blood pressure and heart output.

Question 22

What is serotonin?

Answer 22

• It is a neurotransmitter with multiple roles: pain perception, affective disorders, regulation of sleep, temperature, & BP
• Also called 5-hydroxytryptamine

Question 23

What is methylphenidate?

Answer 23

• Treats ADHD & narcolepsy
• This medicine is a stimulant; blocks dopamine transporter

Question 24

What are Paxil and Prozac?

Answer 24

-Antidepressants; work by blocking the serotonin transporter (like methylphenidate blocks the dopamine transporter), which increases synaptic serotonin levels.