Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-1 The biosynthetic origins of purine ring atoms.

Pag

e 10

69

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-2 The metabolic pathway for the de novo biosynthesis of IMP.

Pag

e 10

71

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-3 The proposed mechanism of formylglycinamide ribotide (FGAM) synthetase.

Pag

e 10

72

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-4 IMP is converted to AMP or GMP in separate two-reaction pathways.

Pag

e 10

74

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-5 Control network for the purine biosynthesis pathway.

Pag

e 10

75

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-6 The biosynthetic origins of pyrimidine ring atoms.

Pag

e 10

77

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-7 Metabolic pathway for the de novo synthesis of UMP.

Pag

e 10

77

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-8 Reactions catalyzed by eukaryotic dihydroorotate dehydrogenase.

Pag

e 10

78

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-9 Proposed catalytic mechanism for OMP decarboxylase.

Pag

e 10

79

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-10 Synthesis of CTP from UTP.

Pag

e 10

80

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-11 Regulation of pyrimidine biosynthesis. The control networks are shown for (a) E. coli and (b) animals.

Pag

e 10

80

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-12a Class I ribonucleotide reductase from E. coli. (a) A schematic diagram of its quaternary structure.

Pag

e 10

82

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-12b Class I ribonucleotide reductase from E. coli. (b) The X-ray structure of R22.

Pag

e 10

82

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-12c Class I ribonucleotide reductase from E. coli. (c) The binuclear Fe(III) complex of R2.

Pag

e 10

82

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-12d Class I ribonucleotide reductase from E. coli. (d) The X-ray structure of the R1 dimer.

Pag

e 10

82

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-13 Enzymatic mechanism of ribonucleotide reductase.

Pag

e 10

83

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-14a Ribonucleotide reductase regulation. (a) A model for the allosteric regulation of Class I RNR via its oligomerization.

Pag

e 10

85

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-14b Ribonucleotide reductase regulation. (b) The X-ray structure of the R1 hexamer, which has D3 symmetry, in complex with ADPNP as viewed along its 3-fold axis.

Pag

e 10

85

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-14c Ribonucleotide reductase regulation. (c) The R1·ADPNP hexamer as viewed along the vertical 2-fold axis in Part b.

Pag

e 10

85

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-15 X-Ray structure of human thioredoxin in its reduced (sulfhydryl) state.

Pag

e 10

86

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-16 Electron-transfer pathway for nucleoside diphosphate (NDP) reduction.

Pag

e 10

87

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-17a X-Ray structures of E. coli thioredoxin reductase (TrxR). (a) The C138S mutant TrxR in complex with NADP+.

Pag

e 10

87

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-17b The C135S mutant thioredoxin reductase (TrxR) in complex with AADP+, disulfide-linked to the C35S mutant of Trx.

Pag

e 10

87

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-18a X-Ray structure of human dUTPase. (a) The molecular surface at the substrate binding site showing how the enzyme differentiates uracil from thymine.

Pag

e 10

89

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-18b X-Ray structure of human dUTPase. (b) The substrate binding site indicating how the enzyme differentiates uracil from cytosine and 2-deoxyribose from ribose.

Pag

e 10

89

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-19 Catalytic mechanism of thymidylate synthase.

Pag

e 10

90

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-20 The X-ray structure of the E. coli thymidylate synthase–FdUMP–THF ternary complex.

Pag

e 10

91

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-21 Regeneration of N5,N10-methylenetetrahydrofolate.

Pag

e 10

91

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-22 Ribbon diagram of human dihydrofolate reductase in complex with folate.

Pag

e 10

91

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-23 Major pathways of purine catabolism in animals.

Pag

e 10

93

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-24a Structure and mechanism of adenosine deaminase. (a) A ribbon diagram of murine adenosine deaminase in complex with its transition state analog HDPR.

Pag

e 10

94

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-24b Structure and mechanism of adenosine deaminase. (b) The proposed catalytic mechanism of adenosine deaminase.

Pag

e 10

94

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-25 The purine nucleotide cycle.

Pag

e 10

95

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-26a X-Ray structure of xanthine oxidase from cow’s milk in complex with salicylic acid. (a) Ribbon diagram of its 1332-residue subunit.

Pag

e 10

95

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-26b X-Ray structure of xanthine oxidase from cow’s milk in complex with salicylic acid. (b) The enzyme’s redox cofactors and salicylic acid (Sal).

Pag

e 10

95

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-27 Mechanism of xanthine oxidase.

Pag

e 10

96

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-28 Degradation of uric acid to ammonia.

Pag

e 10

97

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-29 The Gout, a cartoon by James Gilroy (1799).

Pag

e 10

97

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-30 Major pathways of pyrimidine catabolism in animals.

Pag

e 10

98

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-31 Pathways for the biosynthesis of NAD+ and NADP+.

Pag

e 10

99

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-32 Biosynthesis of FMN and FAD from the vitamin precursor riboflavin.

Pag

e 11

00

Voe

t Bio

chem

istr

y 3e

© 2

004

John

Wile

y &

Son

s, In

c.

Figure 28-33 Biosynthesis of coenzyme A from pantothenate, its vitamin precursor.

Pag

e 11

01