Download Amino Acid Metabolism

Role of Amino Acids
• Protein monomeric units
• Energy source
• Precursors of other biological
molecules
In Mammals
Plants and
bacteria can
produce all of
them
3
Amino acids are precursors
4
Amino acids are precursors
5
CO2
Glycine
Aspartate
7
6
(amine)
5
1
N
N
8
2
10
N -Formyl-FH4
N
3
4
N
9
Glutamine (amide)
N10-Formyl-FH4
4
Glutamine
3
5
N
Aspartate
6
2
CO2
N
1
Biosynthesis of Amino Acids
The nitrogen cycle
8
Biosynthesis of Amino Acids
Nitrogen Fixation -> Microorganism
9
Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
Major Ammonium ion carrier
10
Biosynthesis of Amino Acids
11
Biosynthesis of Amino Acids in Bacteria and Plants
Essential ones are in bold letters
12
Biosynthesis of Amino Acids in Bacteria and Plants
13
Biosynthesis of Amino Acids:
Transaminations
Amino Acid1 + a-Keto Acid2
NH3 +
-
O 2 CCH 2 CH 2 CHCO 2 -
Amino Acid2 + a-Keto
Acid1
O
R-CCO 2 -
+
Glutamate
Pyridoxal phosphate (PLP)Dependent Aminotransferase
O
O 2 CCH 2 CH2 CCO 2 a-Ketoglutarate
14
+
NH2
R-CHCO 2 -
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
Amino Acid Metabolism
17
Fate of the C-Skeleton of Amino Acids
18
Fate of the C-Skeleton of Amino Acids
19
Fate of the C-Skeleton of Amino Acids
Aromatic amino acids need oxygenases
+ O2
20
Fate of Nitrogen in Different Organism
21
Overall Urea Cycle
(Liver)
3ATP
NH 3 +
HCO 3–
+
H2C
COO –
C
–
+
H3N
COO
H
Aspartate
2ADP + 2P i + AMP + PP i
O
H2N
C
NH 2
Urea
+
HC
–OOC
COO –
CH
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
O
HO
C
ADP
O
O– +
Bicarbonate
(CO2)
–
O
P
O–
O
ADP
O
HO
C
OP
Carbonyl-P
Displacement of Phosphate by NH3
Pi
O
HO
C
OP
Carbonyl-P
+
NH 3
O
H2N
C
O–
Carbamate
Phosphorylation of Carbamate by ATP
ATP
O
H2 N
C
O–
Carbamate
ADP
O
H2 N
C
OP
Carbamyl Phosphate
Ornithine Transcarbamylase
(OTC)
(Mitochondrion)
O
NH 2
C
NH 3+
O
H2N
C OP +
Carbamoyl P
(CH 2)3
+H N
3
C
COO –
NH
Pi
(CH 2)3
+H N
3
C
COO –
H
H
Ornithine
Citrulline
Non-standard amino acids
(not present in proteins)
Citrulline Carrier
(Ornithine Antiport)
Argininosuccinate Synthetase
(Cytosol)
O
NH 2
H2N
C
NH
ATP
(CH 2)3
+
H3N
C
COO –
H2C
+
+
H3N
C
COO –
COO –
H
H
Citrulline
Aspartate
C
H2C
H
N C
COO –
H
NH
AMP + PP i
COO –
(CH 2)3
+
H3N
C
COO –
H
Argininosuccinate
Mechanism
Aspartate
H 2C
AM P
P
P
O
NH2
3N
AM P O
H2N
C
H
COO–
AM P
H2N
C
NH
NH
NH
(CH2)3
(CH2)3
C
COO–
H
Citrulline
PPi
+H N
3
C
COO–
H
Citrullyl-AMP
Activation of oxygen atom as a leaving group
+H
3N
C
H 2C
H
N C
C
(CH2)3
+H
+
NH2
COO–
C
COO–
COO–
H
COO–
H
Argininosuccinate
Ammonium Ion is Converted
into Urea
Urea cycle
33
The Urea Cycle is Linked to the Citric Acid Cycle
NH4+
34