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
1) branched chain: Val, Leu, Ile
2) aromatic: Phe (→ Tyr), Trp
3) basic: His, Arg, Lys
4) sulfur-containing: Met (→ Cys)
5) other: Thr
„10“
Essential amino acids PVT TIM HALL
1) branched chain: Val, Leu, Ile
2) aromatic: Phe (→ Tyr), Trp
3) basic: His, Arg, Lys
4) sulfur-containing: Met (→ Cys)
5) other: Thr
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 proteosynthesis
body proteins AAs pool N-compound synthes.
de novo biosynthesis degradation (E,glc,fat)
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
Insertion of an inorganic nitrogen to organic comp.in a human metabolism
Synthesis of AAs in a human body- 5 substrates -
1. oxaloacetate → Asp, Asn
2. αααα-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 αααα-ketoGlt → Glu
2. amidation
Asp → Asn Glu → Gln
3. synthesis from other amino acids
Phe → Tyr Ser → Gly Glu → Pro
Met + Ser → Cys
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
Transamination reaction! REVERSIBLE !
enzymes: amino transferases
coenzyme: pyridoxal phosphate (vit. B6 derivative)
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
alanine aminotransferase(ALT = GPT)
aspartate aminotransferase(AST = GOT)
Amino transferases important in medicine („transaminases“)
glutamine synthetase
„amidation“of glutamate
= side chain carboxylic group of Glu is converted
to amide group
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
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
Synthesis of Tyr from Phe
The figure is from http://www.biocarta.com/pathfiles/GlycinePathway.asp (Jan 2007)
Synthesis of serine and glycineglycolysis
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
Formation of activated methionine= S-adenosylmethionine (SAM)
SAM is used as –CH3 group donorin 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://www.biocarta.com/pathfiles/Cysteine2Pathway.asp (Jan 2007)
The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)
B12
Regeneration of Met
(vitamins: folate+B12)
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 (adrenaline, noradrenaline, dopamine)
2) Trp → serotonin (= 5-hydroxytryptamine)
3) His → histamine
4) Ser → etanolamine → choline → acetylcholine
5) Cys → cysteamine
Asp → ββββ-alanine
Glu → γγγγ-aminobutyrate (GABA)
coenzyme A
TEST / Choose correct statement(s)
a) valine is a branched chain amino acid
b) serine contains thiol group in its side chain
c) glutamate is an essential amino acid
d) tryptophan is a precursor of catecholamines
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. αααα-ketoglutarate ←←←← Glu, Gln, Pro, Arg, His
4. succinyl-CoA ←←←← Val, Ile, Met, Thr
5. fumarate ←←←← Phe, Tyr
6. acetyl-CoA ←←←← Ile
7. acetoacetyl-CoA ←←←← Lys, Leu, Phe, Tyr, Trp
glucogenic AAs
ketogenic AAs
The figure is from http://www.biocarta.com/pathfiles/glucogenicPathway.asp (Jan 2007)
The entrance of amino acids into the citrate cycle
The figure is from http://www.biocarta.com/pathfiles/asparaginePathway.asp (Jan 2007)
An example of AA degradation to produce intermediate of the citrate cycle
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 αααα-ketoGlt + NH3)
enzyme: glutamate dehydrogenase (GMD = GLD)
Glutamine is principaltransport 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
The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_ammonia-transport.jpg(Jan 2007)
Metabolism of amino nitrogen
The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)
GLUTAMATE DEHYDROGENASE
removes amino group from carbon skeleton of Glu in the liver
1. –NH2 from AAs was transfered by transamination → Glu
2. free ammonia is released by oxidative deamination of Glu
Transport and detoxification 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
TEST / The products can be formed from carbon skeleton of the amino acids:
a) aspartate → oxaloacetate
b) lysine → glucose
c) alanine → fat
d) glutamine → αααα-ketoglutarate
TEST / Amino nitrogen released from carbon skeletons of AAs can be transported in
blood as
a) NH4+
b) alanine
c) glutamine
d) urea
Urea (ornithine) cycle
= detoxification pathway (NH3 is toxic for brain)
• proceeds only in the liver
• is localized in mitochondria /cytoplasm
• carbamoyl phosphate synthetase I (= mitoch.)
• can acidify the organism (consumes HCO3-)
• needs energy (3 ATP, but 4 energy rich bonds)
• is connected with citrate cycle through fumarate
• urea is end product of –NH2 metabolism (→ urine)
The figure is from http://www.biocarta.com/pathfiles/ureacyclePathway.asp (Jan 2007)
Detoxification of ammonia in the liver
The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_TCA-Urea_link.jpg(Jan 2007)
Interconnection of the urea cycle with the citrate cycle
• arginineN-acetylglutamatesynthetase
• N-acetylglutamatecarbamoyl phosphatesynthetase I(= mitochondrial)
inhibitionactivationregulatory enzyme
Regulation of urea cycle
allosteric regulation + enzyme induction by protein rich diet or by metabolic changes during starvation
Urea synthesis is inhibited by acidosis– HCO3
- is saved
TEST / Detoxification of ammonia in a human body includes
a) urea cycle proceeding only in the liver
b) cleavage of glutamine in the liver and the kidneys
c) consumption of energy in a form of ATP
d) formation of ornithine from citrulline and carbamoyl phosphate