Amino Acid Metabolism

SUSI ENDRINI, Ph.D

1. Biosintesis Asam Amino Non esensial
(sec. Nutrisi)
2. Katabolisme Protein dan Nitrogen Asam
Amino
3. Katabolisme Kerangka Karbon pada
Asam Amino
4. Konversi Asam Amino menjadi Produk
Khusus
 Non-Essential Amino Acids
in Humans
• Not required in diet
• Can be formed from a-keto acids by
transamination and subsequent reactions
• Alanine • Glycine
• Asparagine • Proline
• Aspartate • Serine
• Glutamate • Cysteine (from Met*)
• Glutamine • Tyrosine (from Phe*)
* Essential amino acids
 Essential Amino Acids in
Humans
• Required in diet
• Humans incapable of forming requisite
carbon skeleton
• Arginine* • Lysine
• Histidine* • Methionine
• Isoleucine • Threonine
• Leucine • Phenylalanine
• Valine • Tryptophan
* Essential in children, not in adults
 Biosynthesis of Amino Acids:
Transaminations
Amino Acid1 +a-Keto Acid2 Amino Acid2 +a-Keto Acid1

NH3 + O
-
O 2 CCH 2 CH 2 CHCO 2 - + R-CCO 2 -
Glutamate
Pyridoxal phosphate (PLP)-
Dependent Aminotransferase

O
NH2
-
O 2 CCH 2 CH2 CCO 2 - +
R-CHCO 2 -
a-Ketoglutarate
 COO COO

COO CH2 COO CH2

CH2 CH2 CH2 CH2

HC NH3+ + C O C O + HC NH3+

COO COO COO COO

aspartate a-ketoglutarate oxaloacetate glutamate

Aminotransferase (Transaminase)
• Example of a Transaminase reaction:
• Aspartate donates its amino group,
becoming the a-keto acid oxaloacetate.
• a-Ketoglutarate accepts the amino group,
becoming the amino acid glutamate.
 COO COO

CH2 CH2

CH3 CH2 CH3 CH2

HC NH3+ + C O C O + HC NH3+

COO COO COO COO

alanine a-ketoglutarate pyruvate glutamate

Aminotransferase (Transaminase)

In another example, alanine becomes

pyruvate as the amino group is transferred to
a-ketoglutarate.
Transaminations: Role of PLP
CO2 -

CHO H N CHCH2 CH2 CO2-

C
HO CH2 OPO3-2
HO CH2 OPO3-2

H3 C
N H3 C
+ N
H +
NH3 + H2 O H
-
O 2 CCH 2 CH 2 CHCO 2 - Tautomerization

O CO2 -
-
O 2 CCH 2 CH 2 CCO 2 - N CCH2 CH2 CO2-
CH2 NH2 CH2
HO CH2 OPO3-2 HO CH2 OPO3-2

H3 C N H2 O H3 C
+ N
+
H H
 Transaminations

Glutamate Glutamate-Pyruvate
Aminotransferase
a-Ketoglutarate
+ +
Pyruvate Alanine

Glutamate-Oxaloacetate
Glutamate Aminotransferase a-Ketoglutarate
+ +
Oxaloacetate Aspartate
 Amino Acids Formed From
a-Ketoglutarate
O
-
O 2 CCH 2 CH2 CCO 2 -
a-Keto- 4 Steps
Transamination or
glutarate Glutamate
dehydrogenase
+ CO2 -
N
NH3 +
H H Proline
- - 5 Steps
O 2 CCH 2 CH 2 CHCO 2
Glutamate NH3+
+
Glutamine
H3 NCH2 CH2 CH2 CHCO 2 - Ornithine
synthase
Urea Cycle
O NH3 + NH2 NH3+
+
H2 NCCH 2 CH 2 CHCO 2 - H2 N=C-HNCH2 CH2 CH2 CHCO 2 - Arginine
Glutamine Guanidino group
 Formation of Serine
CO 2 - CO 2 -
Dehydrogenase
Glycolysis
Glucose H C OH C=O
NAD+ NADH +
CH2OPO3-2 H+
CH2 OPO3-2
3 Steps 3-Phospho- 3-Phospho-
glycerate hydroxypyruvate
Pyruvate Inhibits Glutamate
Transaminase
a-Ketoglutarate
-
CO 2 CO 2 -
Phosphatase
H C NH3 +
H C NH3+

CH2 OH CH2OPO3-2
Serine (Ser) 3-Phosphoserine
Conversion of Serine to Glycine
H

Dihydrofolate H2 N N N
reductase
CO 2 -
Folate N
N CH 2 NHR
H C NH3 +
OH
H Serine
Tetrahydrofolate CH2 OH
(FH4)
Serine hydroxymethyl
transferase (PLP-dep.)
H
N
Key intermediate CO 2 -
in biosynthesis of N CH 2 Glycine
H C NH3 +
purines and N
formation of H2 C H
thymine Important in
N5, N10-Methylene FH4
biosynthesis of heme
and porphyrins
PROLIN
 Cysteine

Methionine
Synthase NH3+
NH3+ (Vit. B12-dep.) -
- HSCH 2CH 2CHCO 2 + 5-Methyl
CH 3SCH 2CH 2CHCO 2 + FH4 FH4
Methionine L-Homocysteine
(Essential) CO 2 -
Cystathionine
H C NH3 + Serine
b-synthase
CH2 OH
(PLP-dep.)

Cystathionine NH3+
OH NH3+ lyase -
SCH 2CH 2CHCO 2
CH 3CHCH 2CO 2
-
+ HSCH 2CHCO 2
-
CH2CHCO2-
Cystathionine
b-Hydroxy- Cysteine NH3+
butyrate (Non-essential)
 Tyrosine
Phenylalanine H
H2N N N H
(Essential)
Tetrahydrobiopterin
H
NH3 + + HN
N CHCHCH3
CH2 CHCO2 -
O H HO OH
O2 Phenylalanine-4- NADP+
Monooxygenase
(Phenylalanine
H2O NADPH + H+
hydroxylase)
HO
H2N N N
NH3 + Dihydrobiopterin
+
CH2CHCO2 - HN
N CHCHCH3
Tyrosine H
(Non-essential) O HO OH