Biochemistry
6th Edition
ISBN: 9781305577206
Author: Reginald H. Garrett, Charles M. Grisham
Publisher: Cengage Learning
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Chapter 26, Problem 3P
Allosteric Regulation of Purine and Pyrimidine Biosynthesis Illustrate the key points of regulation in (a) the biosynthesis of IMP, AMP, and GMP; (b) E. coli pyrimidine biosynthesis; and (c) mammalian pyrimidine biosynthesis.
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Why is de novo biosynthesis of purines markedly elevated in patients with a
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5-Fluoruracil is converted to methotrexate by a DPD deficiency, leading
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HGPRT increases pyrimidine salvage and thereby increases purine
biosynthesis as a result.
Increased purine biosynthesis is the result of ATP hydrolysis during the
production of cyclic AMP.
3) Histone deacetylases (HDACs) are zinc-dependent enzymes that catalyse the conversion of
acetyllysine to lysine.
e)
HN
a) Propose the mechanism for the HDAC-catalysed reaction.
b) What is the role of zinc ion in HDAC catalysis?
c)
d)
f)
HDAC
NH₂
Draw the pH-activity profile for HDAC-catalysed conversion of acetyllysine to lysine.
Explain.
Suggest two acetyllysine analogues that are substrates for HDACs. One should be a better
substrate than acetyllysine, whereas the other one should be a worse substrate than
acetyllysine. Explain.
Mutations in the HDAC sequence could lead to a loss of the catalytic function. Which
mutations are problematic?
Lysine acetylation is a reversible reaction using acetyl-CoA as a co-substrate. Which
coenzymes are required for synthesis of acetyl-CoA in nature? Propose the mechanism.
Chymotrypsin, trypsin, and elastase all share the same catalytic mechanism, but have different
specificities.
(a) These proteases are considered serine proteases because the active sites contain serine, histidine
and aspartate. Describe the roles that each of these amino acid residues play in hydrolyzing protein
substrates.
(b) The active site pockets of chymotrypsin, trypsin, and elastase are shown in the image below.
Based on the image, which side chain of the amino acids would they prefer to cleave respectively, Ala,
Arg, or Trp? Explain your answers.
Val 216
Val 190
Asp 189
Chymotrypsin
Trypsin
Elastase
Chapter 26 Solutions
Biochemistry
Ch. 26 - Prob. 1PCh. 26 - Prob. 2PCh. 26 - Allosteric Regulation of Purine and Pyrimidine...Ch. 26 - Inhibition of Purine and Pyrimidine Metabolism by...Ch. 26 - Prob. 5PCh. 26 - Allosteric Regulation of Ribonucleotide Reductase...Ch. 26 - Prob. 7PCh. 26 - Prob. 8PCh. 26 - Prob. 9PCh. 26 - Prob. 10P
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