Transcript Metabolism of amino acids Vladimíra Kvasnicová Classification of proteinogenic AAs -metabolic point of view 1) biosynthesis in a human body  nonessential (are synthesized) 

Metabolism of amino acids
Vladimíra Kvasnicová
Classification of proteinogenic AAs
-metabolic point of view
1) biosynthesis in a human body
 nonessential (are synthesized)
 essential (must be present in a diet)
2) degradation within cells
 glucogenic (Glc can be formed from their carbon sceleton)
 ketogenic (= AAs degraded to acetyl-CoA)
Essential amino acids
„10“
1) branched chain:
Val, Leu, Ile
2) aromatic:
Phe
3) basic:
His, Arg, Lys
4) sulfur-containing:
Met
5) other:
Thr
(→ Tyr),
(→ Cys)
Trp
Essential amino acids
PVT TIM HALL
1) branched chain:
Val, Leu, Ile
2) aromatic:
Phe
3) basic:
His, Arg, Lys
4) sulfur-containing:
Met
5) other:
Thr
(→ Tyr),
(→ Cys)
Trp
Essential / conditionally essential /
nonessential amino acids
essential:
Val, Leu, Ile, Thr, Phe, Trp, His, Arg, Lys, Met
noness.:
Gly, Ala, Pro, Ser, Tyr, Asn, Gln, Asp, Glu, Cys
Essential / conditionally essential /
nonessential amino acids
essential:
Val, Leu, Ile, Thr, Phe, Trp, His, Arg, Lys, Met
noness.:
Gly, Ala, Pro, Ser, Tyr, Asn, Gln, Asp, Glu, Cys
AAs ~ organically bound nitrogen
dietary proteins
body proteins
de novo biosynthesis
proteosynthesis
AAs pool
N-compound synthes.
degradation (E,glc,fat)
Insertion of an inorganic nitrogen to organic comp.
in a human metabolism
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
Synthesis of AAs in a human body
- 5 substrates -
1. oxaloacetate
→ Asp, Asn
2. -ketoglutarate → Glu, Gln, Pro, (Arg)
3. pyruvate
→ Ala
4. 3-phosphoglycerate → Ser, Cys, Gly
5. Phe
→ Tyr
Synthesis of AAs in a human body
- important reactions -
1. transamination
Pyr → Ala
OA → Asp
-ketoGlt → Glu
2. amidation
Asp → Asn
Glu → Gln
3. synthesis from the other amino acids
Phe → Tyr
Met + Ser → Cys
Ser → Gly
Glu → Pro
Transamination reaction
! REVERSIBLE !
enzymes: amino transferases
coenzyme: pyridoxal phosphate (vit. B6 derivative)
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
Amino transferases important in medicine
(„transaminases“)
alanine aminotransferase
(ALT = GPT)
aspartate aminotransferase
(AST = GOT)
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
„amidation“
of glutamate
= side chain carboxylic
group of Glu is converted
to amide group
glutamine synthetase
GLUTAMINE
= the most important
transport form af amino
nitrogen in blood
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
Synthesis of
ASPARAGINE
needs glutamine as
–NH2 group donor
(it is not ammonia as
in the Gln synthesis)
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
Synthesis of Tyr from Phe
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
glycolysis
Synthesis of serine and glycine
The figure is from http://www.biocarta.com/pathfiles/GlycinePathway.asp (Jan 2007)
Formation of activated methionine
= S-adenosylmethionine (SAM)
SAM is used as –CH3 group donor
in metabolic methylations
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
Synthesis of Cys from Met and Ser
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
The figure is from http://www.biocarta.com/pathfiles/Cysteine2Pathway.asp (Jan 2007)
Regeneration of
Met
B12
(vitamins: folate+B12)
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
Some amino acids are used for
synthesis of other N-compound:
1) Gln, Asp, Gly → purines, pyrimidines
2) Gly → porphyrines, creatine (+ Arg and Met)
3) Arg → NO
4) Cys → taurine
The figure was adopted from Devlin, T. M. (editor): Textbook of
Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc.,
New York, 1997. ISBN 0-471-15451-2
Decarboxylation of AAs gives monoamines
(= biogenic amines)
1) Tyr → catecholamines
2) Trp → serotonin
(adrenaline, noradrenaline, dopamine)
(= 5-hydroxytryptamine)
3) His → histamine
4) Ser → etanolamine → choline → acetylcholine
5) Cys → cysteamine
Asp → -alanine
coenzyme A
Glu → -aminobutyrate (GABA)
Choose essential amino acids
a) Asp, Glu
b) Val, Leu, Ile
c) Ala, Ser, Gly
d) Phe, Trp
Choose essential amino acids
a) Asp, Glu
b) Val, Leu, Ile
c) Ala, Ser, Gly
d) Phe, Trp
Choose amino acids from which the
other amino acid can be synthesized in
a human body
a) valine → leucine
b) aspartate → asparagine
c) phenylalanine → tyrosine
d) methionine + serine → cysteine
Choose amino acids from which the
other amino acid can be synthesized in
a human body
a) valine → leucine
b) aspartate → asparagine
c) phenylalanine → tyrosine
d) methionine + serine → cysteine
The compound(s) can be synthesized
from the amino acid
a) tyrosine → serotonin
b) serine → ethanolamine
c) tryptophan → catecholamines
d) cysteine → taurine
The compound(s) can be synthesized
from the amino acid
a) tyrosine → serotonin
b) serine → ethanolamine
c) tryptophan → catecholamines
d) cysteine → taurine
Degradation of amino acids (AAs)
1) -NH2 group removing from AA
2) detoxification of the amino group
3) metabolism of carbon sceleton of AA
 7 products
7 degradation products of AAs
1. pyruvate  Gly, Ala, Ser, Thr, Cys, Trp
2. oxaloacetate  Asp, Asn
3. -ketoglutarate  Glu, Gln, Pro, Arg, His
4. succinyl-CoA  Val, Ile, Met, Thr
5. fumarate  Phe, Tyr
6. acetyl-CoA  Ile
glucogenic AAs
ketogenic AAs
7. acetoacetyl-CoA  Lys, Leu, Phe, Tyr, Trp
The entrance of amino acids into the citrate cycle
The figure is from http://www.biocarta.com/pathfiles/glucogenicPathway.asp (Jan 2007)
An example of AA degradation to produce
intermediate of the citrate cycle
The figure is from http://www.biocarta.com/pathfiles/asparaginePathway.asp (Jan 2007)
Choose glucogenic amino acids
a) alanine
b) lysine
c) leucine
d) glutamine
Choose glucogenic amino acids
a) alanine
b) lysine
c) leucine
d) glutamine
Fate of amino nitrogen derived from AAs
a) in extrahepatic tissues
 transamination (forms mainly Ala and Glu + 2-oxoacids)
 deamination (only some AAs: Ser,Thr,His; releases NH3)
 amidation Glu + NH3 → Gln
(needs ATP)
b) in the liver
 see a)
 oxidative deamination of Glu (forms -ketoGlt + NH3)
enzyme: glutamate dehydrogenase (GMD = GLD)
Glutamine is principal
transport form of amino nitrogen
The figure is from http://www.sbuniv.edu/~ggray/CHE3364/b1c25out.html (Dec 2006)
Transport of
amino nitrogen
from degraded
muscle proteins
excreted
products
The figure was adopted from Devlin, T. M. (editor): Textbook
of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss,
Inc., New York, 1997. ISBN 0-471-15451-2
Glucose-alanine cycle
The figure was adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed.
Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2
Metabolism of amino nitrogen
The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_ammonia-transport.jpg
(Jan 2007)
GLUTAMATE DEHYDROGENASE
removes amino group from carbon sceleton of Glu in the liver
1. –NH2 from AAs was transfered by transamination → Glu
2. free ammonia is released by oxidative deamination of Glu
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
Transport and detoxifikation of amino nitrogen
- SUMMARY • aminotransferases → glutamate or alanine
• glutamine synthetase → glutamine
• glutaminase → glutamate + NH4+
• glutamate dehydrogenase → 2-oxoglutarate + NH4+
• liver: urea cycle → urea
• kidneys: glutaminase → glutamate + NH4+
→ urine
Choose products of the transamination
reactions
a) alanine → pyruvate
b) glutamate → 2-oxoglutarate
c) aspartate → oxaloacetate
d) phenylalanine → tyrosine
Choose products of the transamination
reactions
a) alanine → pyruvate
b) glutamate → 2-oxoglutarate
c) aspartate → oxaloacetate
d) phenylalanine → tyrosine
Glutamate dehydrogenase (GMD)
a) catalyzes conversion of Glu to oxaloacetate
b) is found in mitochondria of hepatocytes
c) produces ammonia
d) needs pyridoxal phosphate as a coenzyme
Glutamate dehydrogenase (GMD)
a) catalyzes conversion of Glu to oxaloacetate
b) is found in mitochondria of hepatocytes
c) produces ammonia
d) needs pyridoxal phosphate as a coenzyme
Choose correct statement(s) about
metabolism of amino acids
a) alanine aminotransferase (ALT) transforms
pyruvate to alanine
b) aspartate aminotransferase (AST) transforms
aspartate to -ketoglutarate
c) glutamine synthetase transforms glutamate to
glutamine
d) glutaminase catylyzes conversion of glutamine
to ammonia and -ketoglutarate
Choose correct statement(s) about
metabolism of amino acids
a) alanine aminotransferase (ALT) transforms
pyruvate to alanine
b) aspartate aminotransferase (AST)
transforms aspartate to -ketoglutarate
c) glutamine synthetase transforms glutamate
to glutamine
d) glutaminase catylyzes conversion of
glutamine to ammonia and -ketoglutarate
If the amino acid is metabolised the
substance is formed:
a) methionine gives homocysteine
b) serine gives glycine and folic acid
derivative: methylene tetrahydrofolate
c) glutamine releases ammonia
d) some amino acides can be degraded to
acetoacetate
If the amino acid is metabolised the
substance is formed:
a) methionine gives homocysteine
b) serine gives glycine and folic acid
derivative: methylene tetrahydrofolate
c) glutamine releases ammonia
d) some amino acides can be degraded to
acetoacetate
The amino acids can be formed from the
citrate cycle intermediates
in a human body
a) -ketoglutarate → glutamate
b) succinyl-CoA → isoleucine
c) oxaloacetate → aspartate
d) malate → threonine
The amino acids can be formed from
the citrate cycle intermediates
in a human body
a) -ketoglutarate → glutamate
b) succinyl-CoA → isoleucine
c) oxaloacetate → aspartate
d) malate → threonine
The amino acids can enter the citrate
cycle as the molecules
a) alanine → → acetyl-CoA
b) aspartate → oxaloacetate
c) valine → → succinyl-CoA
d) glutamine → → -ketoglutarate
The amino acids can enter the citrate
cycle as the molecules
a) alanine → → acetyl-CoA
b) aspartate → oxaloacetate
c) valine → → succinyl-CoA
d) glutamine → → -ketoglutarate
Urea (ornithine) cycle
•
detoxification pathway
•
proceeds only in the liver
•
localized in mitochondria /cytoplasm
•
carbamoyl phosphate synthetase I
•
can acidify an organism
•
needs energy
•
connected with citrate cycle through fumarate
•
urea is end product of –NH2 metabolism
(NH3 is toxic for brain)
(= mitoch.)
(consumes HCO3-)
(3 ATP, but 4 energy rich bonds)
(→ urine)
Detoxication of ammonia in the liver
The figure is from http://www.biocarta.com/pathfiles/ureacyclePathway.asp (Jan 2007)
Interconnection of the urea cycle with the
citrate cycle
The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_TCA-Urea_link.jpg
(Jan 2007)
Regulation of urea cycle
allosteric regulation + enzyme induction by protein rich diet or
by metabolic changes during starvation
regulatory enzyme
activation
carbamoyl phosphate
synthetase I
(= mitochondrial)
 N-acetylglutamate
N-acetylglutamate
synthetase
 arginine
Urea synthesis is inhibited by acidosis
– HCO3- is saved
inhibition
Ornithine cycle
a) proceeds only in the liver
b) produces uric acid
c) includes arginine as an intermediate
d) produces energy in a form of ATP
Ornithine cycle
a) proceeds only in the liver
b) produces uric acid
c) includes arginine as an intermediate
d) produces energy in a form of ATP
In the urea synthesis
a) ammonia reacts with ornithine → citrulline
b) carbamoyl phosphate synthetase I (=
mitochondrial) regulates the cycle
c) aspartate is used as a –NH2 group donor
d) urea is formed – it can be used as an energy
substrate for extrahepatic tissues
In the urea synthesis
a) ammonia reacts with ornithine → citrulline
b) carbamoyl phosphate synthetase I (=
mitochondrial) regulates the cycle
c) aspartate is used as a –NH2 group donor
d) urea is formed – it can be used as an energy
substrate for extrahepatic tissues