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BIOSYNTHESIS OF AMINO ACIDS
Valine
Isoleucine
Leucine
Threonine
Lysine
Methionine
Tryptophane
Phenylalanine
Histidine
These amino acids are not synthesized
in human cells. Therefore, they are
nutritionally essential amino acids.
Their carbon sceleton can not be
synthesized by human cells.
Histidine is synthesized in a limited amount by intestinal bacteria,
therefore, it is semi-essential nutritionally.
Arginine is synthesized in the urea cycle, but the rate is
insufficient to meet the need during growth. However, it is also
considered as semi-essential amino acid.
Amino acids are the precursors of several biologically active compounds!
Glutamate and glycine are, for example, neurotransmitters!
BIOSYNTHETIC FAMILIES OF AMINO ACIDS
IN PLANTS AND IN HUMAN CELLS
Oxaloacetate
Aspartate
Pyruvate
Alanine Valine Leucine
Ribose 5-phosphate
Histidine
Asparagine Methionine Threonine Lysine
Isoleucine
3-Phosphoglycerate
Phosphoenolpyruvate
+
Erythrose 4-phosphate
-Ketoglutarate
Serine
Glutamate
Phenylalanine
Tryptophane
Glutamine Proline Arginine
Tyrosine
Cystein Glycine
THE BIOSYNTHESIS OF NUTRITIONALLY NON-ESSENTIAL
AMINO ACIDS
Their carbon sceleton can be synthesized
from the intermediates of
-ketoglutarate
oxaloacetate
pyruvate
phosphoglycerate
the citric acid cycle
or glycolysis
from other amino acids
Their NH2-group is obtained from glutamate (in most cases with the help
of specific transaminases)
L-glutamate dehydrogenase plays a central role in the biosynthesis of
amino acids, as well, since it can incorporate NH3 into -ketoglutarate.
1, The biosynthesis of glutamate from -ketoglutarate:
Two enzymes contribute to glutamate production:
a, glutamate dehydrogenase
b, transaminases
2, The biosynthesis of glutamine from glutamate:
Glutamine synthase is the other enzyme which can incorporate NH3
in order to save it for organic compounds
Glutamine is a NH2-group donor:
for the purine-ring, for the pirimidine ring
for the NH2-side groups of nucleotides
for aminosugars
for asparagine
3, The biosynthesis of arginine and proline from glutamate:
glutamate -  - semialdehyde
glutamate
slow
ornithine
urea cycle
arginine
(semiessential)
rapid
proline
4, The de novo synthesis of ornithine:
Synthesis of ornithine is an anaplerotic reaction of urea cycle in the absence
of dietary arginine
glutamate
urea
ornithine
carbamoyl
phosphate
arginine
urea cycle
dietary
arginine
- NH2
In the absence of dietary arginine, arginine is used for protein synthesis
and ornithine is the precursor of polyamines, the amount of ornithine
would be decreased in the urea cycle without anaplerotic reaction
The de novo synthesis of ornithine is slow (rate limiting), therefore,
arginine is semi-essential.
5, The biosynthesis of aspartate from oxaloacetate:
COOH
COOH
transaminase
CH2
CH2
glutamate
O = C - COOH
NH2 - C - COOH
H
oxaloacetate
-ketoglutarate
aspartate is an NH2-group donor
for the synthesis of purine-ring
for the synthesis of adenylate
in the urea cycle
aspartate is a precursor of the pyrimidine ring
aspartate
6, Formation of asparagine from aspartate:
COOH
ATP + H2O
CONH2
AMP + PPi
CH2
CH2
glutamine
NH2 - C - COOH
H
NH2 - C - COOH
H
aspartate
asparagine
glutamate
Enzyme: asparagine synthetase
7, The biosynthesis of alanine from pyruvate:
CH3
CH3
transaminase
C
C=O
NH2
glutamate
COOH
COOH
pyruvate
alanine
-ketoglutarate
8, Formation of serine from phosphoglycerate:
COOH
COOH
HC - OH
phospho
-glycerate
CH2 – O – PO32+
phosphoglycerate
dehydrogenase
H2N - CH
CH2 – O – PO32+
H2O
NAD+
NADH +
phospho
-serine
Pi
H+
COOH
C=O
CH2 – O – PO32+
phosphopyruvate
COOH
H2N - CH
CH2 – OH
serine
Serine is a precursor for: glycine, cystein and phospholipids
phosphatase
9, Formation of glycine from serine:
H
H2N – C - COOH
serine
CH2 – OH
tetrahydrofolic acid (FH4)
N5,N10-methylene-FH4
H2O
H2N – CH2 - COOH
glycine
5
10
Conversion of one-carbon units attached to tetrahydrofolate
5
Ser
N
H
Gly
5
NADH + H+
N
10
N
H
N
H2C
H
NADPH + H+
OH
5
H+
N
H
H2O
5
N
N
10
HC
N
10
O=C-H
N10-formyl-FH4
N
CH3
N
10
N5-methyl-FH4
NADP+
C=O formiate
ADP + Pi
NAD+
N5,N10-methylene-FH4
tetrahydrofolate
ATP
10
5
N5,N10-methenyl-FH4
The metabolism of glycine
The major pathway of degradation: glycine cleavage complex
NH2 – CH2 – COOH
CO2
NH3
THF (FH4)
N5,N10-methylene-FH4
active C1
„nonketotic” hyperglycinemia:
- the glycine cleavage complex is deficient
- mental deficiency and many patients do not
survive infancy
Glycine is an „inhibitory” neurotransmitter
Glycine is a precursor for
purine nucleotides
porphyrins
creatine
glycine conjugates
different drugs are conjugated by glycine in the
course of detoxication process
10, Formation of tyrosine from phenylalanine:
OH
phenylalanine
tyrosine
hydroxylase
CH2
NH2 – CH – COOH
CH2
NH2 – CH – COOH
phenylalanine
DOPA
Fumarate + acetoacetate
Phenylalanine hydroxylase
Deficiency: PHENYLKETONURIA
Dopamine
Norepinephrine
Epinephrine
melanine
(pigment)
11, Formation of cysteine from serine:
The carbon skeleton of cysteine is derived
from serine and the SH-group is derived from
the sulphur of methionine
(methinonine is nutritionally essential)
The degradation process of methionine
yields homocysteine
CYSTATION SYNTHASE DEFICIENCY
Hyperhomocysteinemia and atherosclerosis
excess homocysteine can form hymocysteine thiolactone, a highly
reactive compound
CH2
CH2
S
H2N – CH – C = O
Homocysteine thiolactone reacts with free amino groups in low density
lipoprotein (LDL) and causes them to aggregate and be endocytosed
by macrophages. The lipid deposits form atheromas
About 25% of patients with atherosclerosis who exhibit none of the other
risk factors have been found to be deficient in cystatione synthase!!
vitamine B12
DEVLIN
12, Formation of taurine from cysteine:
sulfinoalanine decarboxylase
cysteine dioxygenase.
Taurine is conjugated via its amino terminal group (bile acids)
Neurotransmission, long-term potentiation (LTP) in the striatum/hippocampus
Membrane stabilization,
Taurine and cats
Taurine is an essential dietary requirement for feline health, since cats cannot synthesize the compound. The absence of taurine causes a cat's ret