Picture cards

Question 1

Recall the structure of glutamine and glutamate

Answer 1

Question 2

Recall the transaminase reaction mechanism

Answer 2

Question 3

What is the biosynthetic origin of purine ring atoms?

Answer 3

• C4, C5 and N7 come from a single glycine molecule
• The other atoms are derived from independent precursors
• Formate: 10-formyl-tetrahydrofolate from diet
  
  • Bacterial folate synthesis is inhibited by sulfonamide
  • Humans are not effected by this antibiotic

Question 4

There is tight regulation of pathways synthesizing IMP, ATP and GTP. This controls the production of purine nucleotides and coordinates relative amounts of ATP and GTP.

Give the INHIBITORY effectors for the following points of production

Synthesis of IMP

• PRPP
• 5-phosphoribosylamine

Branch point after IMP

• Synthesis of AMP and GMP
• Synthesis of ATP (excitatory)
• Synthesis of GTP (excitatory)

Answer 4

Synthesis of IMP

• PRPP
  
  • ADP, GDP
• 5-phosphoribosylamine
  
  • ATP, ADP, AMP, GTP, GDP, GMP

Branchpoint after IMP

• AMP and GMP
  
  • AMP, GMP
• ATP
  
  • GTP (stimulates)
• GTP
  
  • ATP (stimulates)

Question 5

Recall the biosynthetic origins of pyrimidine ring atoms

Answer 5

Question 6

Recall the structure of ribonucleotide reductase

Answer 6

Question 7

Give the mechanism for ribonucleotide reductase’s reduction of ribose to deoxyribose

Answer 7

1. The first step involves the abstraction of the 3’- H of substrate 1 by radical Cys439.
2. Subsequently, the reaction involves the elimination of one water molecule from carbon C-2’ of the ribonucleotide, catalyzed by Cys225 and Glu441.
3. In the third step there is a hydrogen atom transfer from Cys225 to carbon C-2’ of the 2’-ketyl radical 3, after previous proton transfer from Cys462 to Cys225. At the end of this step, a radical anionic disulfide bridge and the closed-shell ketone intermediate 4 are obtained. This intermediate has been identified during the conversion of several 2’-substituted substrate analogues, as well as with the natural substrate[14] interacting with enzyme mutants.
4. The next step is the oxidation of the anionic disulfide bridge, with concomitant reduction of the substrate, generating 5.
5. The spin density shifts from the sulphur atoms to the C-3’ atom of the substrate, with simultaneous proton transfer from Glu441 to carbon C-3’.
6. The last step is the reverse of the first step and involves a hydrogen transfer from Cys439 to C-3’, regenerating the initial radical and resulting in the final product 6.

Question 8

How is ribonucleotide reductase regulated?

Answer 8

• Regulation of RNR is designed to maintain balanced quantities of dNTPs. Binding of effector molecules either increases or decreases RNR activity.
• When ATP binds to the allosteric activity site, it activates RNR. In contrast, when dATP binds to this site, it deactivates RNR.
• In addition to controlling activity, the allosteric mechanism also regulates the substrate specificity and ensures the enzyme produces an equal amount of each dNTP for DNA synthesis
  
  • In all classes, binding of ATP or dATP to the allosteric site induces reduction of CDP and UDP
  • dGTP induces reduction of adenosine 5’-diphosphate ADP
  • dTTP induces reduction of GDP

Question 9

Draw the structure of cholesterol

Answer 9

Question 10

Recall a schematic of the synthesis of adrenal steroids (in yellow) and other steroids from cholesterol.

Answer 10