1. Metabolism of amino acids  Department of Biochemistry (J.D.) 2011

3. Asp Ser, Gly, Thr, Ala, Cys, Trp Intermediates of amino acid catabolism pyruvate glucose fumarate succinyl-CoA 2-oxoglutarate oxaloacetate acetoacetate

4. Transamination of alanine alanine aminotransferase Alanine alanine pyruvate 2-oxoglutarate glutamate

7. Hydrolysis of arginine  urea Arginine glutamate n o transamina tion arginine ornithine

9. Synthesis of creatine (1. part) glycin arginine ornithine guanidinoacetate from Greek κρέας (meat) glycine

10. Synthesis of creatine (2. part) N 1 -methylation of guanidinoacetate S-adenosylmethionine (SAM) S-adenosylhomocysteine creatine N -methylguanidine- N -acetate guanidinoacetate

11. N 2 -Phosforylation of creatine kreatin kreatinfosfát ATP creatine creatine phosphate

12. Creatinine is a catabolite of creatine made in non-enzymatic reaction non-enzymatic cyclization dehydratation kreatin creatinine - H 2 O creatine

14. Dehydratation + deamination of serine Serine pyruvate imine enamine

15. Conversion of serine to glycine H 2 O + N 5 N 10 -CH 2 -FH 4 methylene FH 4 serine glycine cofactor: tetrahydrofolate (FH 4 )

16. Transamination of serine and glucose formation reverse reaction: synthesis of serine pathway is different - through ph os ph oserin e serine hydroxypyruvate glycerate 3-P-glycerate glucose 2-oxoglutarate

17. Betain e is made by cholin e oxidation oxida tion De c arboxyla tion of serin e gives ethanolamin e. Methyla tion of ethanolamin e leads to cholin e de c arboxyla tion methyla tion serin e ethanolamin e cholin e betain e cholin e

19. The complete catabolism of glycine C1 fragment (methylene) is transferred to tetrahydrofolate Glycine C O O H C H 2 N H 2 N 5 N 1 0 C H 2 F H 4 + + C O 2 N H 3 F H 4 +

20. Oxidative deamination of glycine glyoxylate oxalate

24. Methionine is methyl ation agent ( homocystein e side product) B 12 ethanolamin e noradrenalin e guanidinace tate methionine S-adenosylmethionine substrate substrate- CH 3 choline adrenalin e creatine homocysteine remethylation Methionine n o transamina tion

25. S -Adenosylmethionine (SAM) contains tr ivalent positively charged s ulfur atom c ation - sulfonium

26. Cysteine is made from methionine methionine homocysteine cystathionine homoserine cysteine condensation with serine cysteine release pyridoxal-P B 12 succinyl-CoA

29. C ystein e catabolism: oxygenation of -SH group cysteine oxygenation cysteine sulfinate cysteic acid decarboxylation transamination hypotaurine taurine oxygenation sulfinylpyruvate Cysteine oxygenation

30. The formation of sulfite under physiol. pH – dissociation only to HSO 3 - sulfite sulfinylpyruvate hydrolytic cleavage of sulfite pyruvate

31. Sulfite oxidase catalyzes sulfate formation cysteine HSO 3 - + H 2 O  SO 4 2- + 3H + + 2e - blood pla s ma (0 . 5 mmol/l) acidify body fluids reduce molybdopterine PAPS urine

32. Distinguish anion S 2- (e.g. ZnS zinc sulfid e) Sulfid e in organic anion SO 4 2- Sulf ate R-S-R dialkylsulfid e Sulfid e organic anion SO 3 2- Sulfit e

33. Transamination of cysteine and sulfan e production CN - SCN - in smokers SO 4 2- sulfhemoglobin sign al mole c ul e ? 2-oxoglutarate cysteine glutamate mercaptopyruvate desulfuration pyruvate

37. β -Alanine is made by the decarboxylation of aspartate - CO 2 β α in the structure of CoA-SH

38. Glutamate with oxaloacetate afford aspartate (transamination) AST reaction produces aspartate for urea synthesis aspartate aminotransferase Glutamate oxaloacetate aspartate  urea glutamate 2-oxoglutarate

39. Dehydrogenative deamination of glutamate is the main producer of ammonia in tissues g lutamate dehydrogenase (GD, GDH, GMD) glutamate 2-iminoglutarate 2-oxoglutarate (CAC)

40. Decarboxylation of glutamate glutamate

41. Compare: GABA vs . GHB GABA GHB g ama- h ydroxy b utyrate, synthetic drug, liquid ecstasy, belongs to “date rape drugs “ , euphoria, sedation - CNS depressant, downer GHB g amma- a mino b utyric a cid, Inhibitory neurotransmitter in the brain, formed by decarboxylation of glutamate GABA

44. Amino acids as neurotransmiter s Chlorid e channels (Cl - ) C ation ic channels (Na + ) GABA Glycin e Glutam ate Aspart ate (Acetylcholin e ) Inhibi tory Excita tion

46. T hree amino acids donate four N atom s in purine bases synthesis fumar ate glutam ate aspartate glycine amide group of glutamine amide group of glutamine

47. Proline is converted to glutamate (and vice versa ) proline glutamate 5-semialdehyde glutamate pyrroline-5-carboxylate oxidation addition of H 2 O ring opening Proline n o transamina tion

48. Hydroxylation of proline with 2-oxoglutarate as reductant - CO 2 proline 2-oxoglutarate 4-hydroxyproline succinate Fe 2+ ascorbate

50. Ca tabolism of histidin e starts with desatura tion and deamination urocanic acid (urocanate) Histidine n o transamin ation

51. Urocanate cleavage affords C 1 fragment FIGLU urocanate N -formiminoglutamate (Figlu) glutamate addition of water oxidative ring splitting

53. Histidine is responsible for buffering actions of proteins p K B = 8 p K A (His) = 6 p K A (His in proteins ) = 6-8

55. Leucine (1) - transamination + decarboxylation Leucine, Isoleucine, Valine (BCAA) branched 2-oxoacid oxidative decarboxylation branched acyl-CoA transamination

56. Leucine (2) - dehydrogenation 2,3-dehydrogenation branched unsaturated acyl

57. Leucine (3) – carboxylation at C4 carboxylation acyl of dicarboxylic branched unsaturated acid

58. Leucine (4) – hydratation of double bond

59. Leucine (5) – splitting the C-C bond in HMG-CoA HMG-CoA lyase acetoacetate

60. Compare the final products of BCAA B 12 B 12 glucogenic succinyl-CoA Valine ketogenic glucogenic acetyl-CoA + succinyl-CoA Isoleucine ketogenic acetyl-CoA + acetoacetate Leucine

62. Lysine catabolism (1) Lysine n o transamina tion lysine 2-oxoglutarate ketimine (Schiff base)

63. Lysine catabolism (2) ketimine hydrogenation dehydrogenation saccharopine aldimine

64. Lysine catabolism (3) hydrolysis aldimine allysine glutamate

65. Lysine catabolism (4) allysine dehydrogenation 2-aminoadipate

66. Lysine catabolism (5) 2-aminoadipate 2-oxoglutarate transamination 2-oxoadipate glutamate

67. Lysine is the substrate for carnitine (the transfer of FA from cytosol to mitochondria) carnitine acylcarnitine

68. Cross-links in collagen hydrogenated aldimine lysine (lysyl residue in polypeptide) dehydrated aldol allysine allysine lysine + hydrogenation products of reaction between the amino groups in side chains of lysine with the modified lysine side chains comprising the aldehyde group (the result of oxidation of lysine to allysine ) – aldol type or aldimine type of cross-links.

69. Formation of fibrin clot during blood coagulation (cross-linking of fibrin) lysine glutamine cross-linking

71. Catabolism (1) Phenylalanine, Tyrosine hydroxylation transamination phenylalanine tyrosine p-hydroxyphenylpyruvate

72. Catabolism (2) p-hydroxy ph enylpyruv ate homogentisate (2,5-dihydroxyphenylacetate) oxidative decarboxylation rearrangement hydroxylation

73. Catabolism (3) oxidative cleavage of aromatic ring dioxygenase maleylacetoacetate

74. Catabolism (4) maleylacetoacetate fumarylacetoacetate isomeration

75. Catabolism (5) fumarylacetoacetate fumarate acetoacetate

77. Metabolites of phenylalanine phenylalanine phenylpyruvate transamination oxid. decarboxylation phenylacetate phenyllactate hydrogenation

79. Hydroxylation of phenylalanine gives tyrosin e phenylalanine tyrosine c o - redu c tant tetrahydrobiopterin e

80. DOPA a nd dopamin e from tyrosine tyrosine dopamine (catecholamine) (3,4-dihydroxyphenylalanine) hydroxylation decarboxylation Tyrosine

82. Two more catecholamines from dopamine Cu 2+ nor- = N -demethyl hydroxylation at C2 N -methylation dopamine noradrenaline adrenaline O 2 , ascorbate

83. Conversion of dopamine to melanin, a dark pigment of skin, hair, fur dopamine dopaquinone melanin multiple condensations

84. Conversion of tyrosin e to thyroxin e bound to thyreoglobulin tyrosine 3’,5’-diiododtyrosine thyroxine

86. Catabolism (1) O 2 Tryptophan n o transamina tion tryptophan oxidative cleavage of aromatic ring N -formylkynurenine

87. Catabolism (2) hydrolysis of amide group formamide hydroxylation formate

88. Catabolism (3) hydrolytic cleavage of alanine 3-hydroxyanthranilate

89. Catabolism (4) 3-hydroxyanthranilate nicotinamide 2-oxoadipate

90. Decarboxylation of tryptophan tryptophan tryptamine

91. Conversion of tryptophan to melatonin sleep-wake cycle the hormone of darkness Trp hydroxylation 5-hydroxytryptophan decarboxylation N -acetylation O -methylation

93. Five vitamins are formed in the body, only four are utilized in tissues, from tryptophan large intestine ( ba cteria) large intestine ( ba cteria) skin, from cholesterol (UV radiation ) large intestine ( ba cteria) – n ot absorbed ! Niacin Biotin Ph yl l o quinone C alciol C obalamin e Where and how produced Vitamin

94. Seven amino acids do not undergo transamination ornithine 2-aminoadipate homoserine glycine alanine glutamate NH 3 (desaturation deamination) Arginine Lysine Methionine Threonine Tryptophan Proline Histidine  -NH 2 group is removed as Amino acid

95. pyruv ate  glu cose urea , NO, creatine ethanolamin e  cholin e  betain e ; donor of 1C fragment , selenocysteine hem e , c reatin e , GSH, c onjuga tion reagent ( e.g . gly c ochol ate ) donor of methyl, c reatin e , homocystein e, cysteine glutathione ( GSH ) , taurin e , SO 4 2- , PAPS, cysteamin e (CoA) d onor of -NH 2 (urea, pyrimidin es ), oxaloacetate, fumar ate , β -alanin e (CoA) NH 4 + , 2-oxoglutar ate , GABA , ornithine NH 4 + , d onor of -NH 2 (synt hesis of glu c osamin e , purin es ) glutamate, hydroxyprolin e glutamate, histamin e , donor of 1C fragment glutamate, allysin e ( collagen ), c arnitin e , c adaverin e fumar ate , c atecholamin es , thyroxin e , melanin s ni c otinamid e , serotonin, melatonin, donor of 1C fragment , indole, skatole Ala Arg Ser Gly Met Cys Asp Glu Gln Pro His Lys Tyr Trp Biochemic ally relevant produ c t A A