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بيوشيمي عموميگروه علوم دامي دانشکده کشاورزي
دانشگاه ياسوجدکتر مختار خواجوی
Amino Acid Metabolism
Role of Amino Acids
• Protein monomeric units• Energy source• Precursors of other
biological molecules
3
In Mammals
Plants and bacteria can
produce all
of them
Amino acids are precursors
4
Amino acids are precursors
5
SOURCE OF EACH ATOM IN THE PURINE RING
N
N
N
N
9
1 8
7 6
5
4
3
2
Glycine
N10-Formyl-FH4
N10-Formyl-FH4
Aspartate (amine)
CO2
Glutamine (amide)
N
N
2
1
3
4
5
6
Aspartate
CO2
Glutamine
SOURCES OF THE ATOMS OF THE PYRIMIDINE RING:
8
Biosynthesis of Amino Acids
The nitrogen cycle
9
Biosynthesis of Amino Acids
Nitrogen Fixation -> Microorganism
10
Major Ammonium ion carrier
Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
11
Biosynthesis of Amino Acids
12
Biosynthesis of Amino Acids in Bacteria and Plants
Essential ones are in bold letters
13
Biosynthesis of Amino Acids in Bacteria and Plants
14
Biosynthesis of Amino Acids: Transaminations
Amino Acid1 + a-Keto Acid2 Amino Acid2 + a-Keto Acid1
NH3+
-O2CCH2CH2CHCO2-
Glutamate
OR-CCO 2
-+
O-O2CCH2CH2CCO 2
-
a-Ketoglutarate
NH2
R-CHCO 2-
+
Pyridoxal phosphate (PLP)-Dependent Aminotransferase
Products of Amino Acid Breakdown
•Glucogenic–Pyruvate–a-
Ketoglutarate–Succinyl-CoA–Fumarate–Oxaloacetate
•Ketogenic –Acetyl-CoA–Acetoacetate
Animals cannot carryout net synthesis of precursors of
gluconeogenesis from acetyl-CoA or acetoacetate
17
Amino Acid Metabolism
18
Fate of the C-Skeleton of Amino Acids
19
Fate of the C-Skeleton of Amino Acids
20
Fate of the C-Skeleton of Amino Acids
Aromatic amino acids need oxygenases + O2
21
Fate of Nitrogen in Different Organism
Classification of Organisms(Nitrogen Excretion Patterns)
• Ammonotelic: ammonia excreting
• Ureotelic: urea excreting• Uricotelic: uric acid excreting
Overall Urea Cycle(Liver)
NH3 + HCO 3– +
H2NC
NH2
O
H3N C COO–
H2C
H
COO–
3ATP 2ADP + 2P i + AMP + PP i
+HC COO–
CH–OOC
Aspartate Urea Fumarate
+
Carbamyl Phosphate Synthetase (CPS)
•CPSI (Mitochondria)–Uses NH3
–Urea Cycle•CPSII (Cytosol)
–Uses Glutamine–Pyrimidine Biosynthesis
Carbamyl Phosphate Synthetase (CPS)
Mechanism
Activation of HCO3– by ATP
HO C
O
O–
Bicarbonate (CO2)
+ –O P
O
O–
O ADP
ADP
HO C
O
OP
Carbonyl-P
Displacement of Phosphate by NH3
HO C
O
OP + NH3
Pi
H2N C
O
O–
CarbamateCarbonyl-P
Phosphorylation of Carbamate by ATP
H2N C
O
O–
ATP ADP
H2N C
O
OP
Carbamyl PhosphateCarbamate
Ornithine Transcarbamylase (OTC)
(Mitochondrion)
H2N C
O
OP + +H3N C COO–
H
(CH2)3
NH3+
Ornithine
Pi
+H3N C COO–
H
(CH2)3
NH
CO NH2
CitrullineCarbamoyl P
Non-standard amino acids (not present in proteins)
Citrulline Carrier(Ornithine Antiport)
Argininosuccinate Synthetase(Cytosol)
+H3N C COO–
H
(CH2)3
NH
CO NH2
Citrulline
+ C+H3N COO–
H
H2C COO–
Aspartate
ATP AMP + PP i
+H3N C COO–
H
(CH2)3
NH
CH2N
H N C
H
COO–
H2C COO–
Argininosuccinate
Mechanism
+H3N C COO–
H
(CH2)3
NH
CO NH2
Citrulline
CH2N COO–
H
H2C COO–
Aspartate
+H3N C COO–
H
(CH2)3
NH
CH2N
H N C
H
COO–
H2C COO–
Argininosuccinate
AMP P P
PPi
+H3N C COO–
H
(CH2)3
NH
CO NH2AMP
Citrullyl-AMP
AMP
+
Activation of oxygen atom as a leaving group
33
Ammonium Ion is Converted into Urea
Urea cycle
34
The Urea Cycle is Linked to the Citric Acid Cycle
NH4+
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