Class 1

1. METABOLISMO DE
PIRIMIDINAS

3. N
N
HO
NH2
N
N
HO
O
N
N
HO
O
CH3
N
N
HO
O
COOH
cytosine
thymine
uracyl
orotic acid

7. Orotate Synthesis

9. Atom assembly of pyrimidine ring

11. Interconversion of Nucleotides
The nucleoside monophosphates are the forms synthesized de novo. The triphosphates are the
most commonly used forms.
The monophosphates are converted to the di- and tri-phosphates by the sequential activities of
nucleoside monophosphate kinases and nucleoside diphosphate kinase. The reactions are
reversible, so the nucleoside mono-, di- and triphosphateforms are in equilibrium.
Nucleoside monophosphate kinases:
 convert nucleoside monophosphates to diphosphates, using ATP as phosphate donor
 nucleoside monophosphate kinases show substrate specificity (different enzymes
phosphorylate AMP, GMP, pyrimidines and deoxynucleotides)
Adenylate kinase: AMP + ATP 2 ADP
Thymidylate kinase: TMP + ATP TDP + ADP
Nucleoside diphosphate kinase:
 converts nucleoside diphosphates to triphosphates, using ATP as phosphate donor
 nucleoside diphosphate kinase (NDK) has broad specificity (one enzyme can phosphorylate
purine and pyrimidine ribo-and deoxyribonucletides)
examples:
GDP + ATP GTP + ADP
dGDP + ATP dGTP + ADP
UDP + ATP UTP + ADP

17. 2’-Deoxynucleotide production

18. dTMP Synthesis

24. OROTACIDURIA
inherited disorder of pyrimidine synthesis
caused by a deficiency of the enzyme of
orotate-phosphoribosyltransferase and
decarboxylase.
Symptoms:
–excess of orotic acid and its excretion
with urine (1.0-1.5 g)
-mental and physical retardation
-megaloblastic anemia

25. – Treatment: patients are fed uridine
U  UMP  UDP  UTP
UTP inhibits carbamoyl phosphate synthase II, preventing the
biosynthesis and accumulation of orotic acid
O
OHOH
CH2
O
P
O
P
O
-O
-O
O-
-
O3PO
O
C
NH
O
HN
COOC
C
H
C
O
PPi
Orotate 5-phosphoribosyl-1-pyrophosphate (PRPP)

29. BUILDING BLOCKS

31. Nucleotide Structure
Phosphate (P) lacks
protons at neutral pH,
hence nucleotides
have a negative charge
Phosphate attached
to 5’C in most
nucleotides
Base attached to 1’C
OH attached to 3’C in
both nucleotides and
deoxynucleotides
OH attached to 2’C in
nucleotides BUT H in
deoxynucleotides
1’
3’
4’
5’
2’

32. Purine and Pyrimidine Structure
• Pyrimidines are planar
• Purines are nearly planar
• Numbering is different
Nucleotide Structure
https://skfb.ly/6M8oJ
https://skfb.ly/6Jqn7

33. Nucleotide Structure: Bases
N
N N
H
N
NH2
adenine
NH
N N
H
N
O
NH2
guanine
N
N
HO
NH2
N
N
HO
O
CH3
cytosine uracyl
N
N
HO
O
thymine
Purines Pyrimidines

34. theobromine caffeine
Nucleotide Structure
theophylline thiamine

38. Nucleotide Structure: Sugars

39. Ribose stereochemistry