Anabolism of Nitrogen Compounds

1
Anabolism of Nitrogen Compounds
2
Nitrogen CycleFig. 22-1 Lehninger POB 4th Ed.
3
Nitrogenase is a Very Important Enzyme

• FeS complexes as seen before
• MoFe complexes
• Mg2 cofactor
• doesnt occur in aerobic environment plant
  produces leghemoglobin

4
Movement of NH4

• Just like catabolism, distribution is through Glu
  and Gln
• Glu not synthesized de novo in mammals, instead
  ?KG is aminated via glutamate dehydrogenase, a
  mitochondrial enzyme.

5
Glutamine Synthetase is Control Point for
Nitrogen Anabolism

• Heavily regulated allosteric inhibition by
  carbamoyl phosphate, Trp, AMP, CTP, His, Gly,
  Ala, glucosamine-6-phosphate

6
2nd Mechanism of Glutamine Synthetase Regulation
Unique AMP Attached to TyrFig. 22-7(a)
Lehninger POB 4th Ed.

• Adenylated form is inactive form
• Cascade leads to adenylation as shown in 22-7(b)

7
Essential Amino Acids

• PVT TIM HALL

8
Number of Enzymes Required to Synthesize Amino
AcidsTable 30-2, Harpers ROB, 24th Ed.

• Essential
• Phe 10
• Val 1 (7shared)
• Trp 5 (8 shared)
• Thr 6
• Ile 8 (6 shared)
• Met 5 (4 shared)
• His 6
• Arg 7
• Lys 8
• Leu 3 (7 shared)
• Total 59

• Nonessential
• Ala 1
• Asp 1
• Asn 1
• Glu 1
• Gln 1
• Pro 3
• Ser 3
• Gly 1
• Cys 2
• Tyr 1
• Total 15

9
Semiessential Amino Acid
10
Cys Synthesis
11
Cys Synthesis
12
Cys SynthesisHomocysteine Generation
13
Creatine Synthesis
14
Creatine Synthesis
15
Creatine Function
16
Creatine Degradation
17
Serotonin (5HT)
18
DOPA/Dopamine
19
Questions from last time
20
Epinephrine
21
Histamine
22
Polyamines
23
Polyamines
24
Polyamines
25
Polyamines
26
Glutathione Synthase
27
Heme Metabolism(Liver Mitochondria)
28
Heme Metabolism(Liver Cytoplasm)
29
Heme Metabolism
30
Heme Metabolism
31
Heme Metabolism
32
Conjugation

• Bilirubin diglucuronide
• Glucuronic acid
• Added in open chain form
• Added to propyl groups
• Increases water solubility

33
De novo Purine Synthesis 1
34
De novo Purine Synthesis 2
35
De novo Purine Synthesis 3
36
De novo Purine Synthesis 4
37
De novo Purine Synthesis 5
38
De novo Purine Synthesis 6
39
De novo Purine Synthesis 7
40
De novo Purine Synthesis 8
41
De novo Purine Synthesis 9
42
De novo Purine Synthesis 10
43
De novo Purine Synthesis 11
44
De novo Purine Synthesis 12a
45
De novo Purine Synthesis 13a
46
De novo Purine Synthesis 12b
47
De novo Purine Synthesis 13b
48
De novo Pyrimidine Synthesis 1
49
De novo Pyrimidine Synthesis 2
50
De novo Pyrimidine Synthesis 3
51
De novo Pyrimidine Synthesis 4
52
De novo Pyrimidine Synthesis 5
53
De novo Pyrimidine Synthesis 6
54
De novo Pyrimidine Synthesis 7
55
De novo Pyrimidine Synthesis 8
56
Loose Ends Ribonucleotide Reductase
57
Loose Ends T Synthesis
58
Loose Ends T Synthesis
59
Loose Ends T Synthesis
60
Summary of Nucleotide Synthesis

• Purines built up on ribose
• PRPP synthetase key step
• 13 enzyme activities on 3 polypeptides (to IMP)
• Pyrimidine rings built, then ribose added
• Carbamoyl phosphate synthetase II key step
• Multifunctional enzyme (mammals) all but
  dihydroorotate DH (CAD)
• Salvage is importantrapid turnover of mRNA

61
Summary of Nucleotide SynthesisSource of Atoms
62
Purine Salvage Occurs by Two Mechanisms From
Bases
63
Purine Salvage Occurs by Two Mechanisms From
Nucleosides
64
Pyrimidine Salvage Occurs Only From the
Nucleosides
65
Regulation is Complex

• PRPP pool size is a major point of de novo
  synthesis
• PRPP stimulates pyrimidine synthesis
• TDP inhibits PRPP production

66
AMP, GMP and IMP Feedback Inhibit Allosterically
67
AMP and GMP Inhibit Their Own Synthesis From IMP
68
Ribonucleotide Reductase is Heavily
RegulatedFig. 22-40(a) Lehninger POB 4th Ed.

• Note dimeric protein
• Complicated mechanism involving free radicals
• Overall activity controlled by ATP/dATP

69
Ribonucleotide Reductase is Heavily
RegulatedFig. 36-10, Harpers ROB, 24th Ed.

• Note dimeric protein
• Complicated mechanism involving free radicals
• Overall activity controlled by ATP/dATP
• Allosteric control

70
Pyrimidine Synthetic Enzyme Gene Expression is
Also Regulated

• Multifunctional protein (dihydroorotate
  dehydrogenase separate)
• coordinate repression and derepression (will talk
  about later)