Biosynthesis of Amino

Acid
Dr. Asep
Sudarman
 OVERVIEW OF AMINO ACID
METABOLISM
ENVIRONMENT ORGANIS
M
Bio-
Ingeste synthesi Protein
d s
2 3
protein 1
a
AM IN
O b
c ACIDS c
Purines
Degradatio
n
Pyrimidine
Carbo s
Nitrogen (required)
skeletons
n Porphyrins
(glucogeni
(ketogenic)
Ure Used c)
energ
a acetoacetat fory pyruvate
e acetyl α-
CoA ketoglutarate
succinyl-CoA
fumarate
oxaloacetate
 Amino Acid
Metabolism
•Metabolism of the 20 common amino acids is
considered from the origins and fates of
their:
(1) Nitrogen atoms
(2) Carbon skeletons
•For mammals:
Essential amino acids must be obtained
from diet
Nonessential amino acids - can be
synthesized
 Amino Acid Requirements of Humans
------------------------------------------------------------------
--
Nutritionally Essential Nutritionally Nonessential
Argininea Alanine
------------------------------------------------------------------
-- Histidine Asparagine
Isoleucine Aspartate
Leucine Cysteine
Lysine Glutamate
Methionine Glutamine
Phenylalanine Glycine
Threonine Proline
Tryptophan Serine
Valine Tyrosine
--------------------------------------------------------------------
-
a “
Nutritionally semiessential.” Synthesized at
rates inadequate to support growth of children.
 AMINO ACID
METABOLISM
• KETOGENI
C
– LEU
– LYS
• GLUCOGENIC
ALL NON- + HIS, VAL, MET
ESSENTIALS
• BOTH
– ILE
– PH
E
– TH
R
– TRP
– TYR
 AMINO ACID
•
BIOSYNTHESIS
ALL ARE SYNTHESIZED FROM COMMON
METABOLIC INTERMEDIATES
• NON-ESSENTIAL
– TRANSAMINATION OF -KETOACIDS THAT ARE AVAILABLE
AS COMMON INTERMEDIATES
• ESSENTIAL
– THEIR -KETOACIDS ARE NOT COMMON INTERMEDIATES
(ENZYMES NEEDEDTO FORM THEM ARE LACKING)
• SO TRANSAMINATION ISN’T AN OPTION
– BUT THEYARE PRESENT IN COMMON PATHWAYS OF MICRO-
ORGANISMS AND PLANTS
 AMINO ACID
BIOSYNTHESIS OVERVIEW
(USE OF COMMON
INTERMEDIATES)
Overview
(cont) Pyruvat
e
 Biosynthetic
Families
Metabolic Precursors Amino
Acids
- Glutamat
ketoglutarate e
Glutamine
Proline
Arginine
3- Serine
Phophoglycerate Glycine
Cystein
e
 Biosynthetic Families
(cont)
Metabolic Precursors Amino
Acids
Oxaloacetat Aspartate, Asparagine
e Methionine,
Threonine, Lysine

Pyruvat Alanine, Valine,

e Leucine Isoleucine
 Biosynthetic Families
(cont)
Metabolic Precursors Amino
Acids
Phosphoenolpyruvate Tryptophan
and erythrose 4- Phenlyalani
phosphate ne
Tyrosine
Ribose 5- Histidin
phophate e
 Ketoglutarate
Family
a-Ketoglutarate

Glutamate

Glutamine Proline Arginine

 -ketoglutarate to
glutamate/glutamine
• Reductive amination of -ketoglutarate by glutamate
dehydrogenase occurs in mitochondria.
• A second important route in assimilation of
ammonia is via glutamine synthetase
Glutamate synthase transfers a
nitrogen to -ketoglutarate
 Ketoglutarate
Family
a-Ketoglutarate

Glutamate

Glutamine Proline Arginine

Synthesis of
Proline
Synthesis of
Proline
Synthesis of
Arginine
Synthesis of
Arginine
3-Phosphoglycerate
Family
3-Phosphoglycerate

Serine

Glycine Cysteine
Synthesis of Serine and
Glycine
Synthesis of
Cysteine
 Oxoloacetate
Family
Oxaloacetate

Aspartate

Asparagine Methionine Lysine Threonine

 Synthesis of Aspartate and
Asparagine

Oxaloacetat Transamination from

Aspartate
Amidation with
e glutamate
Glutamine
donating NH4+

Asparagin
e
 Pyruvate
Family
Pyruvate

Alanine Valine Leucine Isoleucine

 Synthesis of
Alanine

Pyruvat Transamination from

Alanin
e glutamate e
 THE PYRUVATE
FAMILY
• “BRANCHED CHAIN AMINO ACIDS”
– LEU
– ILE
– VAL
• VAL, ILE: SAME PATHWAY AFTER 1st STEP
• LEU PATHWAY BRANCHES FROM VAL PATHWAY
• FINAL STEPS ALL CATALYZEDBY AMINO- TRANSFERASES
– GLU IS THE AMINO DONOR
 Phosphoenolpyruvate and erythrose 4-
phosphate Family

Phosphoenolpyruvate
+
erythrose 4-phosphate

Chorismate

Tryptophan Tyrosine Phenylalanine

Synthesis of
Chorismate
Synthesis of
Tryptophan
Synthesis of Tyrosine and
Phenylalanine
Synthesis of Tyrosine and
Phenylalanine (cont)
 Peptide
Proteins and peptidessare polymers made up of
amino acid units (residues) that are linked together
through the formation of amide bonds (peptide
bonds) from the amino group of one residue and the
carboxylate of a second residue

By convention, peptide
sequences are written left to
right from the N-terminus to the
C-terminus

backbone