Metabolism of amino acids - exercise - Vladimíra Kvasnicová

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

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

„10“ Essential amino acids 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

needs glutamine as –NH2 group donor 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 intermediates in a human body -ketoglutarate → glutamate succinyl-CoA → isoleucine oxaloacetate → aspartate malate → threonine

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

Amphibolic character of 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 urea it is the end product of degradation of amino nitrogen (liver → kidneys → urine)

Transport of amino nitrogen from degraded muscle proteins products excreted 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

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 (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

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 principal transport form of amino nitrogen The figure is from http://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 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

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

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 regulatory enzyme activation inhibition carbamoyl phosphate synthetase I (= mitochondrial) N-acetylglutamate N-acetylglutamate synthetase arginine Urea synthesis is inhibited by acidosis – HCO3- is saved