058 CHAPTER 27 Nucleosides, Nucleotides, and Nucleic Acids
ANTIBIOTICS THAT ACT BY
INHIBITING TRANSLATION
Puromycin is a naturally occurring antibiotic. It is
one of several antibiotics that act by inhibiting translation.
Puromycin mimics the -CCA-aminoacyl portion of a tRNA.
If, during translation, the enzyme is fooled into transferring the
growing peptide chain to the amino group of puromycin rather
than to the amino group of the incoming -CCA-aminoacyl
tRNA, protein synthesis stops. Because puromycin blocks pro-
tein synthesis in eukaryotes as well as in prokaryotes, it is poi-
sonous to humans and therefore is not a clinically useful
antibiotic. To be clinically useful, an antibiotic must affect pro-
tein synthesis only in prokaryotic cells.
3 ¿
3 ¿
O
N
H
OH
N N
N
H 3 CCH 3
N
N
HO
O
CH 2 CHC
NH 2
puromycin
CH 3 O
Clinically useful
antibiotics Mode of action
Tetracycline Prevents the aminoacyl-tRNA from binding to the ribosome
Erythromycin Prevents the incorporation of new amino acids into the protein
Streptomycin Inhibits the initiation of protein synthesis
Chloramphenicol Prevents the new peptide bond from being formed
27.14 Why DNA Contains Thymine Instead of Uracil
In Section 25.8 we saw that dTMP is formed when dUMP is methylated, with coenzyme
-methylenetetrahydrofolate supplying the methyl group. Because the incorpora-
tion of the methyl group into uracil oxidizes tetrahydrofolate to dihydrofolate, dihydrofo-
late must be reduced back to tetrahydrofolate to prepare the cofactor for another catalytic
cycle. The reducing agent is NADPH. Every NADPH formed in a biological organism
can drive the formation of three ATPs, so using an NADPH to reduce dihydrofolate
comes at the expense of ATP. This means that the synthesis of thymine is energetically
expensive, so there must be a good reason for DNA to contain thymine instead of uracil.
The presence of thymine instead of uracil in DNA prevents potentially lethal muta-
tions. Cytosine can tautomerize to form an imine, which can be hydrolyzed to uracil
(Section 18.6). The overall reaction is called a deaminationsince it removes an amino
group.
tautomerization
cytosine uracil
N
O
NH 2
N
H
N
H
N
H
HN
+ NH 3
H 2 O
O
NH
HN
O
O
N^5 ,N^10
N
R′
dUMP
R′ = 2 ′-deoxyribose-5-P
HN + N (^5) ,N (^10) -methylene-THF + dihydrofolate
thymidylate
synthase
O
O
N
R′
HN
O
CH 3
O
dihydrofolate + NADPH + H+ tetrahydrofolate + NADP+
dihydrofolate
reductase
dTMP