1. Metabolism of amino acids Vladimíra Kvasnicová

2. 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)

3. 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“

4. 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

5. 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

6. 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 proteinsproteosynthesis body proteins AAs poolN-compound synthes. de novo biosynthesisdegradation (E,glc,fat)

7. The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html Insertion of an inorganic nitrogen to organic comp. in a human metabolism

8. 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

9. Synthesis of AAs in a human body - important reactions - 1.transamination Pyr → AlaOA → Asp  -ketoGlt → Glu 2.amidation Asp → AsnGlu → Gln 3.synthesis from the other amino acids Phe → Tyr Ser → Gly Glu → Pro Met + Ser → Cys

10. The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html Transamination reaction ! REVERSIBLE ! enzymes: amino transferases coenzyme: pyridoxal phosphate (vit. B6 derivative)

11. 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“)

12. 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

13. Synthesis of ASPARAGINE needs glutamine as –NH 2 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

14. The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html Synthesis of Tyr from Phe

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

16. The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html Formation of activated methionine = S-adenosylmethionine (SAM) SAM is used as –CH 3 group donor in metabolic methylations

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

18. The figure is from http://www.biocarta.com/pathfiles/Cysteine2Pathway.asp (Jan 2007)http://www.biocarta.com/pathfiles/Cysteine2Pathway.asp

19. The figure is from http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html (Jan 2007)http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html B12 Regeneration of Met (vitamins: folate+B 12 )

20. 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

21. 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 →  - alanine Glu →  -aminobutyrate (GABA) coenzyme A

22. Choose essential amino acids a)Asp, Glu b)Val, Leu, Ile c)Ala, Ser, Gly d)Phe, Trp

23. Choose essential amino acids a)Asp, Glu b)Val, Leu, Ile c)Ala, Ser, Gly d)Phe, Trp

24. 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

25. 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

26. The compound(s) can be synthesized from the amino acid a)tyrosine → serotonin b)serine → ethanolamine c)tryptophan → catecholamines d)cysteine → taurine

27. The compound(s) can be synthesized from the amino acid a)tyrosine → serotonin b)serine → ethanolamine c)tryptophan → catecholamines d)cysteine → taurine

28. Degradation of amino acids (AAs) 1)-NH 2 group removing from AA 2)detoxification of the amino group 3)metabolism of carbon sceleton of AA  7 products

29. 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 7.acetoacetyl-CoA  Lys, Leu, Phe, Tyr, Trp glucogenic AAs ketogenic AAs

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

31. The figure is from http://www.biocarta.com/pathfiles/asparaginePathway.asp (Jan 2007)http://www.biocarta.com/pathfiles/asparaginePathway.asp An example of AA degradation to produce intermediate of the citrate cycle

32. Choose glucogenic amino acids a)alanine b)lysine c)leucine d)glutamine

33. Choose glucogenic amino acids a)alanine b)lysine c)leucine d)glutamine

34. 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 NH 3 )  amidation Glu + NH 3 → Gln (needs ATP) b)in the liver  see a)  oxidative deamination of Glu (forms  -ketoGlt + NH 3 ) enzyme: glutamate dehydrogenase (GMD = GLD)

35. Glutamine is principal transport form of amino nitrogen The figure is from http://www.sbuniv.edu/~ggray/CHE3364/b1c25out.html (Dec 2006)http://www.sbuniv.edu/~ggray/CHE3364/b1c25out.html

36. 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

37. 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

38. The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_ammonia-transport.jpg (Jan 2007)http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_ammonia-transport.jpg Metabolism of amino nitrogen

39. The figure is from http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html (Jan 2007)http://web.indstate.edu/thcme/mwking/nitrogen-metabolism.html GLUTAMATE DEHYDROGENASE removes amino group from carbon sceleton of Glu in the liver 1. –NH 2 from AAs was transfered by transamination → Glu 2. free ammonia is released by oxidative deamination of Glu

40. Transport and detoxifikation of amino nitrogen - SUMMARY - aminotransferases → glutamate or alanine glutamine synthetase → glutamine glutaminase → glutamate + NH 4 + glutamate dehydrogenase → 2-oxoglutarate + NH 4 + liver: urea cycle → urea kidneys: glutaminase → glutamate + NH 4 + → urine

41. Choose products of the transamination reactions a)alanine → pyruvate b)glutamate → 2-oxoglutarate c)aspartate → oxaloacetate d)phenylalanine → tyrosine

42. Choose products of the transamination reactions a)alanine → pyruvate b)glutamate → 2-oxoglutarate c)aspartate → oxaloacetate d)phenylalanine → tyrosine

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. 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

52. 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

53. Urea (ornithine) cycle detoxification pathway (NH 3 is toxic for brain) proceeds only in the liver localized in mitochondria /cytoplasm carbamoyl phosphate synthetase I (= mitoch.) can acidify an organism (consumes HCO 3 - ) needs energy (3 ATP, but 4 energy rich bonds) connected with citrate cycle through fumarate urea is end product of –NH 2 metabolism ( → urine)

54. The figure is from http://www.biocarta.com/pathfiles/ureacyclePathway.asp (Jan 2007)http://www.biocarta.com/pathfiles/ureacyclePathway.asp Detoxication of ammonia in the liver

55. The figure is from http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_TCA-Urea_link.jpg (Jan 2007) http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch18_TCA-Urea_link.jpg Interconnection of the urea cycle with the citrate cycle

56. regulatory enzymeactivationinhibition carbamoyl phosphate synthetase I (= mitochondrial)  N-acetylglutamate N-acetylglutamate synthetase  arginine Regulation of urea cycle allosteric regulation + enzyme induction by protein rich diet or by metabolic changes during starvation Urea synthesis is inhibited by acidosis – HCO 3 - is saved

57. 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

58. 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

59. 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 –NH 2 group donor d)urea is formed – it can be used as an energy substrate for extrahepatic tissues

60. 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 –NH 2 group donor d)urea is formed – it can be used as an energy substrate for extrahepatic tissues