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Takusagawa’s Note
Chapter 20 (Summary)
Summary of Chapter 20
1. Transamination
• Major problem in amino acid degradation is elimination of -NH2 since NH3 from -NH2 is
very toxic.
• There are two ways to remove -NH2 from amino acids.
1. Transamination: R-NH2 → Glu-NH2 → Asp-NH2 →→ Urea
+
→ α-ketoglutarate + NH →→ Urea
2. Oxidative deamination: R-NH → Glu-NH NAD
2
2
3
• Transaminases contain co-enzyme, pridoxal-5’-phosphate (PLP), which is covalently
attached to the Lys residue of the enzyme via Schiff base linkage (E-Lys-PLP).
• Aminotransferase reaction: AA1 ↔ α-Keto acid1
1. Transimination: E-Lys-PLP + AA1 ↔ [E-PLP-AA1] ↔ E-Lys + PLP-AA1
2. Tautomerization: PLP-AA1 ↔ α-Keto acid1-PMP [PMP = PLP-NH2]
3. Hydrolysis: α-Keto acid1-PMP + H2O ↔ α-Keto acid1 + PMP
• Reverse aminotransferase reaction: α-Keto acid2 ↔ AA2
3’. α-Keto acid2 + PMP ↔ α-Keto acid2-PMP
2’. α-Keto acid2-PMP ↔ PLP-AA2
1’. PLP-AA2 + E-Lys ↔ [E-PLP-AA2] ↔ E-Lys-PLP + AA2
• Ammonia is expeled as urea (amminals) and uric acid (birds).
2. Urea cycle
• Urea is formed from
1. Ammonia (NH3) from oxidative deamination
2. Amine (-NH2) of Asp
3. Bicarbonate (HCO3-)
• Reactions
1. Formation of carbamoyl phosphate by carbamoyl phosphate synthetase.
HCO3- + NH3 + 2ATP → H2N-CO(OPO32-) + 2ADP + Pi
2. Condensation of ornitine and carbamoyl to form citrulline by ornithine transcarbamoylase.
Ornitine + H2N-CO(OPO32-) → Citrulline + Pi
3. Condensation of citrulline and Asp to form argininosuccinate by argininosuccinate
synthetase
Citrulline + Asp + ATP → Argininosuccinate + AMP + PPi
4. Cleavage of argininosuccinate to Arg and fumarate by argininosuccinase
Argininosuccinate → Arg + Fumarate
5. Hydrolysis of Arg to urea and ornitine by arginase
Arg + H2O → Urea + Ornitine
• Overall reaction uses 4 “high energy” phosphate bond hydrolysis.
CO2 + NH3 + Asp + 2H2O + 3ATP → Urea + Fumarate + 2ADP + AMP + 2Pi + PPi (→ 2Pi)
• Oxidation of urea cycle produces 2NADH (= 6ATP).
• Krebs bicycle: Urea cycle and aspartate-argininosuccinate shunt of citric acid cycle.
• Urea cycle is regulated by [N-acetyl-glutamate] which activates carbamoyl phosphate
synthetase.
1. Breakdown of proteins produces amino acids including Glu.
2. Glu is acetylated by acetyl-glutamate synthase.
3. N-acetyl-glutamate activates urea cycle.
1
Takusagawa’s Note
Chapter 20 (Summary)
• Ammonia produced in all tissues are transported by Gln and Ala.
1. NH4+ + Glu + ATP → Gln + ADP + Pi + H+
in tissue
+
+
in liver
Gln + H2O → Glu + NH4 ; NH4 → Urea
2. Glucose-alanine cycle:
Glucose → Pyruvate + Glu → Ala + α-Ketoglutarate
in Tissue

Ala + α-Ketoglutarate → Pyruvate + Glu
 in Liver
Glu → NH3 → Urea

Pyruvate → Glucose
2. Amino acid’s skeleton metabolism
• 20 amino acids are converted to 7 common intermediates. Those are:
Both glucogenic and ketogenic intermediate
1. Pyruvate
Ala, Cys, Gly, Ser, Thr, Tyr
2. α-ketoglutarate
Glucogenic intermediates (form glucose)
3. Succinyl-CoA
Arg, Glu, Gln, His, Pro, Ile, Met, Val, Asp,
4. Fumarate
Phe, Tyr, Asn
5. Oxaloacetate
6. Acetyl-CoA
7. Acetoacetate
Ketogenic intermediates (form ketone bodies)
Ile, Leu, Thr, Lys, Phe, Trp, Tyr
3. Metabolism of C1 unit (Tetrahydrofolate cofactors)
• THF functions to transfer C1 unit in several oxidation states.
• C1 units carried by THF are:
Methyl (-CH3); Methylene (-CH2-); Formyl (-CH=O); Formimino (-CH=NH);
Methenyl (-CH=)
• C1 units are donated from Ser, Gly, HCO3-, His to THF.
• Sulfonamides competitively inhibit bacterial synthesis of THF, because those structures are
analogues to p-aminobenzoic acid moiety of THF.
4. Synthesis of some amino acids.
• Ala, Asn, Asp, Cys, Glu, Gln, Gly, Pro, Ser, Tyr are nonessential amino acids.
• Glycerate-3-phosphate →→→ Ser → Gly → Cys
• Pyruvate → Ala
• α-Ketoglutarate → Glu → Gln; Glu→→→Pro
• Oxaloacetate → Asp → Asn
THF→5,10-methylene THF
→ Gly
• Ser  
• Phe → Tyr by phenylalanine-4-monooxygenase.
• Glutamine synthetase is a central control point in the nitrogen metabolism, since Gln is an
amino group donor and a storage of ammonia.
1. Feedback inhibition: His, Tyr, carbamoyl phosphate, AMP, CTP, glucosamine-6phosphate
(all end products from Gln) are allosteric inhibitors. Ala, Ser and Gly also inhibit since
high concentration of these amino acids is a signal of saturation of the citric acid cycle .
2. Covalent modification (adenylylation-deadenylylation and uridylylation-deuridylylation)
• Inhibition under conditions of nitrogen excess.
2
Takusagawa’s Note
Chapter 20 (Summary)
5.
•
•
6.
•
•
7.
•
1. High [Gln] activates uridylyl-removing enzyme in uridylyltransferase.
2. Uridylyl-removing enzyme removes UMP from adenylyltransferase.
3. Adenylyltransferase inactivates glutamine synthetase by adenylylation.
• Activation under conditions of nitrogen limitation.
1. High [α-ketoglutarate] activates uridylyltransferase.
2. Uridylyltransferase uridylylates adenylyltransferase.
3. Uridylylated adenylyltransferase activates glutamine synthetase by removes AMP.
S-Adenosylmethionine (SAM)
is synthesized from Met and ATP.
is the major methyl group donor
Porphyrin synthesis
Precursors of porphyrin biosynthesis are Gly and succinyl-CoA.
Enzyme contains
1. Gly + Succinyl-CoA → δ-Aminolevlinate (ALA) + CO2 + CoA
PLP.
2. 2ALA → Porphobilinogen (PBG)
3. 4PBG → Hydroxymethylbilane → Uroporphyrinogen III → Various hemes
Overall heme biosynthesis is taken place in both cytosol and mitochondrion.
Various amine biosynthesis
Some of amines are important neurotransmitters, hormones, and reducing agents.
Glu → γ-Aminobutyric acid (GABA)
His → Histamine
Trp → Serotonin
Tyr → Dihydroxyphenylalanine (L-DOPA) → Dopamine → Norepinephrine → Epinephrine
Glu + Cys + Gly → Glutathione (GSH)
3