Metabolism of amino acids

Metabolism of amino acids- exercise - Vladimíra Kvasnicová

Choose essential amino acids • Asp, Glu • Val, Leu, Ile • Ala, Ser, Gly • Phe, Trp

Essential amino acids „10“ • branched chain: Val, Leu, Ile • basic: His, Arg, Lys • aromatic: Phe(→ Tyr),Trp • sulfur-containing: Met(→ Cys) • other: Thr

Choose amino acids from which the other amino acid can be synthesized in a human body • valine → leucine • aspartate → asparagine • phenylalanine → tyrosine • methionine + serine → cysteine

Choose amino acids from which the other amino acid can be synthesized in a human body • valine → leucine leucine is the essential AA • aspartate → asparagine • phenylalanine → tyrosine • methionine + serine → cysteine

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)

Synthesis of Cys from Met and Ser The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)

The amino acids can be formed from the citrate cycle intermediatesin a human body • -ketoglutarate→ glutamate • succinyl-CoA →isoleucine • oxaloacetate → aspartate • malate →threonine

The amino acids can be formed from the citrate cycle intermediatesin a human body • -ketoglutarate→ glutamate • succinyl-CoA →isoleucine Ile is the essential AA • oxaloacetate → aspartate • malate →threonine Thr is the essential AA

Amphibolic characterof citrate cycle The figure is from http://www.tcd.ie/Biochemistry/IUBMB-Nicholson/gif/13.html (Dec 2006)

The compound(s) can be synthesized from the amino acid • tyrosine → serotonin • serine → ethanolamine • tryptophan → catecholamines • cysteine → taurine

The compound(s) can be synthesized from the amino acid • tyrosine → serotonin Tyr → catecholamines • serine → ethanolamine formed by decarboxylation • tryptophan → catecholamines Trp → serotonin • cysteine → taurine

taurin is used in conjugation reactions in the liver– it is bound to hydrophobic substances to increase their solubility (e.g. conjugation of bile acids) 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

If the amino acid is metabolised the substance is formed: • methionine gives homocysteine • serine gives glycine and folic acid derivative: methylene tetrahydrofolate • glutamine releases ammonia • some amino acides can be degraded to acetoacetate

If the amino acid is metabolised the substance is formed: • methionine gives homocysteine • serine gives glycine and folic acid derivative: methylene tetrahydrofolate • glutamine releases ammonia • some amino acides can be degraded to acetoacetate = one of ketone bodies

Regeneration of Met (vitamins: folate+B12) B12 The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)

Synthesis of serine and glycine glycolysis The figure is from http://www.biocarta.com/pathfiles/GlycinePathway.asp(Jan 2007)

Choose products of the transamination reactions • alanine → pyruvate • glutamate → 2-oxoglutarate • aspartate → oxaloacetate • phenylalanine →tyrosine

Choose products of the transamination reactions • alanine → pyruvate • glutamate → 2-oxoglutarate • aspartate → oxaloacetate • phenylalanine →tyrosine it is not transamination

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

Amino nitrogen released from carbon sceletons of AAs can be transported in blood as • NH4+ • alanine • glutamine • urea

Amino nitrogen released from carbon sceletons of AAs can be transported in blood as • NH4+physiologically up to 35 µmol/l(NH3 + H + NH4+) • alanine formed by transamination from pyruvate • glutamine the most important transport form of –NH2 • ureait is the end product of degradation of amino nitrogen (liver → kidneys → urine)

Transport of amino nitrogen from degraded muscle proteins productsexcreted with urine 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 alanine transfers both the carbon sceleton for gluconeogenesis and –NH2 group 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

GLUTAMINE = the most important transport form af amino nitrogen in blood it transfers two amino groups released by degradation of AAs glutamine synthetase 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

Choose glucogenic amino acids • alanine • lysine • leucine • glutamine

7 degradation products of AAs • pyruvateGly, Ala, Ser, Thr, Cys, Trp • oxaloacetateAsp, Asn • -ketoglutarate  Glu, Gln, Pro, Arg, His • succinyl-CoA  Val, Ile, Met, Thr • fumarate  Phe, Tyr • acetyl-CoA  Ile • acetoacetyl-CoA  Lys, Leu, Phe, Tyr, Trp glucogenic AAs ketogenic AAs

Glutamate dehydrogenase (GMD) • catalyzes conversion of Glu to oxaloacetate • is found in mitochondria of hepatocytes • produces ammonia • needs pyridoxal phosphate as a coenzyme

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)

Choose correct statement(s) about metabolism of amino acids • alanine aminotransferase (ALT) transforms pyruvate to alanine • aspartate aminotransferase (AST) transforms aspartate to -ketoglutarate • glutamine synthetase transforms glutamate to glutamine • glutaminase catylyzes conversion of glutamine to ammonia and -ketoglutarate

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

Glutamine is principaltransport form of amino nitrogen The figure is fromhttp://www.sbuniv.edu/~ggray/CHE3364/b1c25out.html (Dec 2006)

The amino acids can enter the citrate cycle as the molecules • alanine → → acetyl-CoA • aspartate →oxaloacetate • valine → → succinyl-CoA • glutamine → →-ketoglutarate

The entrance of amino acids into the citrate cycle The figure is from http://www.biocarta.com/pathfiles/glucogenicPathway.asp (Jan 2007)

Ornithine cycle • proceeds only in the liver • produces uric acid • includes arginine as an intermediate • produces energy in a form of ATP

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)

In the urea synthesis • ammonia reacts with ornithine → citrulline • carbamoyl phosphate synthetase I (= mitochondrial) regulates the cycle • aspartate is used as a –NH2 group donor • urea is formed – it can be used as an energy substrate for extrahepatic tissues

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

Metabolism of amino acids - exercise -