Aa 1

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Aa 1

  1. 1. Catabolism of amino acids Ammnonia detoxification Biosynthesis of non-essential amino acids  Biochemický ústav LF MU (J.D.) 2011
  2. 2. Anabolic and catabolic conversions of AA AA pool Endogenous proteins Food proteins FA  TAG CO 2 + energy glucose signal molecules (hormone, neurotransmiter) purine / pyrimidine bases porphyrines  heme creatine  creatinine arginine  NO and other ... NH 3  NH 4 + carbon skeleton Synthesis of non-essential AA Urea Glutamine CAC GI tract Intracellular degradation nitrogen compound compound without N
  3. 3. Amino acid pool <ul><li>T hree sources of AA pool : </li></ul><ul><li>Proteol ysis of dietary pro tein s (food) </li></ul><ul><li>Proteol ysis of tissue protein s (physiological turnover, more in starvation) </li></ul><ul><li>Synt hesis of non- es s en tial AA (11) </li></ul><ul><li>T hree utilizations of AA pool : </li></ul><ul><li>Synt hesis of tissue and blood plasma protein s ( liver ) </li></ul><ul><li>Synt hesis of low-molecular nitrogen compounds (hormones etc.) </li></ul><ul><li>Catabolism: d eamina tion + utiliza tion of carbon skeleton </li></ul><ul><li>T hree utilizations of AA carbon skeleton </li></ul><ul><li>Glu c oneogene sis (in starvation, most AA are glucogenic) </li></ul><ul><li>Synt hesis of FA and TAG (in AA excess) </li></ul><ul><li>Metabolic fuel = gain of energ y (minor utilization) </li></ul>
  4. 4. Degradation of proteins <ul><li>Exogenous proteins </li></ul><ul><li>the lumen of GI tract </li></ul><ul><li>stomach – pepsin </li></ul><ul><li>intestine – pancreatic proteases (trypsin, chymotrypsin etc.) </li></ul><ul><li>Endogenous proteins </li></ul><ul><li>Intracellular proteases </li></ul><ul><li>two systems </li></ul><ul><li>1. Lysosome </li></ul><ul><li>2. Ubiquitin-proteasome </li></ul>Biochemistry II + ph y s iolog y Biochemistry I
  5. 5. pepsin trypsin pepsinogen activated by HCl carboxypeptidases aminopeptidases AA – resorption into portal blood pH 1-2 chymotrypsin, elastase Digestion of dietary proteins proteases are secreted as inactive proenzymes activated by the cleavage of certain peptide sequence
  6. 6. Protein digestion begins in the stomach, acidic environment (pH 1-2) favours denaturation. Proteins undergo proteolysis catalyzed by pepsin. Degradation continues in the lumen of the intestine by pancreatic proteolytic enzymes secreted as inactive proenzymes Digestion is then completed by aminopeptidases located in the plasma membrane (brush border) of the enterocytes. Single amino acids, as well as di- and tripeptides, are transported into the intestinal cells from the lumen and released into the blood.
  7. 7. Enteropeptidase secreted by the mucosa of duodenum initiates the activation of the pancreatic proenzymes
  8. 8. Proteolytic enzymes exhibit the preference for particular types of peptide bonds Proteinases preferentially attacks the bond after: Pepsin aromatic (Phe, Tyr) and acidic AA (Glu, Asp) Trypsin basic AA (Arg, Lys) Chymotrypsin hydrophobic (Phe, Tyr, Trp, Leu) and acidic AA (Glu, Asp) Elastase AA with a small side chain (Gly, Ala, Ser) Peptidases : Carboxy peptidase A nearly all AA ( not Arg and Lys) Carboxy peptidase B basic AA (Arg, Lys) amino peptidase nearly all AA Prolidase proline Dipeptidase only dipeptides
  9. 9. Transcellular transport of AA from intestine to portal blood L-amino acids: about seven specific transporters, symport with Na + D-amino acids (trace amounts): nonspecific diffusion, hydrophilic pores in membranes, D-AA cannot be utilized in the body, they are only catabolized to gain energy Also small oligopeptides (symport with H + ) Na +
  10. 10. Endogenous proteins have different biological half-lives 12 min 1.3 hour 12 hour 2 days 4 days 19 days 23 days several years whole life (?) Ornithine decarboxylase RNA polymerase I AST Prealbumin Lactate dehydrogenase Albumin IgG Collagen Elastin Half-life Protein
  11. 11. Degradation of proteins in lysosomes <ul><li>does not require ATP, non-specific </li></ul><ul><li>e xtracel l ul ar and membr ane proteins </li></ul><ul><li>long-lived intracellular proteins </li></ul><ul><li>extracellular glycoproteins – sialic acid at terminal position on oligosascharide chain is removed = asialoglycoproteins – they are recognized by liver receptors  degrada tion in liver lysosomes </li></ul>
  12. 12. Examples of lysosomal h ydrolas es gly c oside gly c oside gly c oside sulfoester gly c oside peptide peptide peptide phosphodiester ester phosphoester amide Glu c osidas e Gala c tosidas e Hyaluronidas e Arylsulfatas e Lysozym e C athepsin Collagenase Elastase Ribonuclease Lipase Phosphatase Ceramidase Typ e of bond Hydrolas e
  13. 13. Ubiquitin (Ub) targets protein s for proteasome degrada tion <ul><li>small protein, in all cells - ubiquitous </li></ul><ul><li>C-terminus binds Lys of proteins to be degraded ( kiss of death ) </li></ul><ul><li>binding Ub to protein has three phases, with three enzymes E 1 ,E 2 , E 3 </li></ul><ul><li>binding Ub to E 1 -SH requires ATP </li></ul><ul><li>more Ub molecules are attached - polyubi qu itina tion </li></ul><ul><li>Ub-tagged protein is directed to proteasome </li></ul>
  14. 14. The targeting of protein s E1 ubiquitin-activating enzyme (ATP) E2 ubiquitin-conjugating enzyme E3 ubiquitin-protein ligase <ul><li>The N-terminal rule </li></ul><ul><li>Stabiliz ing AA ( long life): </li></ul><ul><li>Met, Ser, Ala, Thr, Val, Gly, Cys </li></ul><ul><li>Destabiliz ing AA ( short life ) : </li></ul><ul><li>Phe, Leu, Asp, Lys, Arg </li></ul><ul><li>PEST protein s : segment s rich in Pro, Glu, Ser, Thr </li></ul>
  15. 15. Proteasome <ul><li>hollow cylindric supramolecule, 28 polypeptides </li></ul><ul><li>four cyclic heptamers (4  7 = 28) </li></ul><ul><li>the caps on the ends regulate the entry of proteins into destruction chamber, upon ATP hydrolysis </li></ul><ul><li>inside the barrel, differently specific proteases hydrolyze target protein into short (8 AA) peptides </li></ul><ul><li>Ub is not degraded, it is released intact </li></ul>
  16. 16. Proteasomes degrade regulatory proteins (short half-life) and abnormal or misfolded proteins Ub + short peptides Protein-Ub AA cytosolic peptidases regulation of cell cycle, apoptosis, angiogenesis
  17. 17. Spatial model of p roteasom e 28 subunits in 4 rings (4 x 7), yellow chains in beta subunits contain proteolytic active sites on N- termini
  18. 18. Bortezomib is inhibitor of proteasom e - boron atom b inds to active site (Thr) ( treatment of m ultiple myelom a ) Synt he tic tripeptid e : pyrazino ic acid -Phe-boro nic acid- Leu boric acid instead of -COOH
  19. 19. Biological value (BV) of proteins refers to how well the body can utilize the proteins we consume Relative amount of nitrogen (%) used to synthesis of endogenous proteins from total protein nitrogen absorbed from food. <ul><li>BV depends on : </li></ul><ul><li>total content of essential AA </li></ul><ul><li>mutual ratios of essential AA </li></ul><ul><li>protein digestibility </li></ul>BV animal prot > BV plant pro t wheat – deficit in Lys, Trp, Thr, Met legumes – deficit in Met, Cys
  20. 20. PDCAAS <ul><li>p rotein d igestibility- c orrected a mino a cid s core </li></ul><ul><li>a recent method based on essential AA requirement and protein digestibility </li></ul><ul><li>reference protein = ideal protein with optimal ratio of all essential AA (often whey or egg white) </li></ul><ul><li>true digestibility (%): amount of nitrogen absorbed from food per total food nitrogen </li></ul>amount of limiting AA in test protein -------------------------------------------------------- × true digestibility (%) amount of the same AA in reference protein
  21. 21. Essential (9) and semiessential (3) amino acids <ul><li>valine, leucine, isoleucine (BCAA) </li></ul><ul><li>threonine (2 C*) </li></ul><ul><li>lysine, histidine (basic) </li></ul><ul><li>phenylalanine, tryptophan (aromatic) </li></ul><ul><li>methionin e (-S-CH 3 ) </li></ul><ul><li>Semiessential AA </li></ul><ul><li>arginine – in childhood </li></ul><ul><li>alanine , glutamin e – in metabolic stress </li></ul><ul><li>about 30 % of methionine need can be substituted by cysteine </li></ul><ul><li>about 50 % of phenylalanine need can be su bstituted by tyrosine </li></ul>
  22. 22. Quality o f some proteins 100 100 80 80 49 54 25 BV (%) 100 100 100 92 68 40 8 Egg white Whey Milk c asein Beef Beans W heat flour Gelatin PDCAAS (%) Protein
  23. 23. Egg white, whey, and gluten <ul><li>Egg white is a viscous solution of globular proteins (ovalbumin, </li></ul><ul><li>ovotransferrin, ovomu c oid, ovomucin, ovoglobulin s , avidin e etc. ) </li></ul>Whey is a by-product in cottage chesse (curd) production a yellowish liquid (riboflavin), after precipitation of casein contains high quality proteins (lactoalbumin, lactoglobulins), B-vitamins, and lactose Gluten is protein fraction in wheat and other cereals, containing mainly gliadin (high content of Pro and Gln). In genetically predisposed people, it may cause autoimmune celiac disease. BL / GF
  24. 24. Quantity of proteins in foodstuffs (%) D aily intake of protein s : 0.8 g/kg 4 0 30 25 25 20 13 10 11 8 4 2 1 Parmesan cheese Emmental cheese Curd L egumes (beans) M eat Eggs Fish Yeast Cereals , r ice M ilk Potatoes Fruits , vegetables
  25. 25. Alternativ e plant protein products Robi Seitan Tofu Tempeh Food ro stlinné bí lkoviny , cereal + rice proteins isolated wheat proteins coagulated s o y milk proteins f erment ed soybeans by Rhizopus oligosporus 22 % 25 % 16 % 20 % Commentary P rotein content
  26. 26. Protein supplements <ul><li>high content of proteins (20 – 90%) </li></ul><ul><li>mainly derived from dried whey </li></ul><ul><li>and/or free AA (BCAA = Val, Leu, Ile) </li></ul><ul><li>it is a metabolic load for: </li></ul><ul><li>digestion (  putrefaction in large intestine, correlates with some types of cancer) </li></ul><ul><li>liver (  urea synthesis), kidneys (excretion of urea, NH 4 + , free AA) </li></ul><ul><li>may be adulterated with anabolic steroids !!! </li></ul>
  27. 27. Catabolic pathway of amino acids Transamination Dehydrogenation + deamination of glutamate Detoxication of ammonia Excretion of nitrogen catabolites
  28. 28. Proteins NH 3 glutam ate glutam ate + urea (ex c re tion by urine ) 2-oxoglutar ate + glutamin e proteol ysis dehydrogena tion + deamina tion detoxi cation in liver deami d a tion in kidney amino acids transamina tion detoxi cation in other tissues NH 4 + (ex c re tion by urine ) NH 4 + (ex c re tion by urine ) deamina tion in kidney Intake, catabolism, and excretion of nitrogen
  29. 29. Transamination transfer of -NH 2 group from one substrate to other <ul><li>most AA (not Lys, Thr, Pro, His, Trp, Arg, Met) </li></ul><ul><li>amino group is transferred from AA to 2-oxoglutarate </li></ul><ul><li>cofactor – pyridoxal phosphate (  Schiff bases) </li></ul><ul><li>reversible reaction  important for synthesis of AA </li></ul>
  30. 30. General scheme of transamination amino acid 2-oxo acid 2-oxoglutarate glutamate aminotransferase pyridoxal phosphate
  31. 31. Pyridoxal phosphate has a reactive aldehyde group aldehyde group covalently linked to enzyme
  32. 32. 1. Phase of transamination AA  oxoacid pyridoxal-P  pyridoxamine-P amino acid oxo acid Schiff base aldimine of pyridoxal Schiff base iminoacid isomeration
  33. 33. 2. Phase of transamination 2-oxoglutarate  glutamate pyridoxamine-P  pyridoxal-P Schiff base aldimine of pyridoxal Schiff base iminoacid 2-oxoglutarate glutamate
  34. 34. In transaminations, nitrogen of most A A is c oncent rated in glutam ate Glutamate then undergoes dehydrogen ation + deamina tion and releases free ammonia NH 3 !
  35. 35. Dehydrogenation + deamination of glutamate is reversible reaction NAD(P) + main source of ammonia in tissues glutamate 2-iminoglutarate 2-oxoglutarate
  36. 36. Glutamate dehydrogenase (GMD, GD, GDH) <ul><li>requires pyridine cofactor NAD(P) + </li></ul><ul><li>GMD reaction is reversible: dehydrogenation with NAD + , hydrogenation with NADPH+H + </li></ul><ul><li>two steps: </li></ul><ul><li>d ehydrogenation of CH-NH 2 to imino group C=NH </li></ul><ul><li>h ydrol ysis of imino group to oxo group and ammonia </li></ul>
  37. 37. <ul><li>D eamina tion of glutamate (GD reaction) in tissues </li></ul><ul><li>Bacterial putrefaction of proteins in the large intestine produces nitrogen catabolites (e.g. biogenic amines + ammonia), ammonia diffuses freely into portal blood  port al blood has high concentration of NH 4 +  eliminated by liver </li></ul>Two main sources of ammonia in organism
  38. 38. Other sources of ammonia: deaminations of various substrates <ul><li>deamination of adenin e </li></ul><ul><li>oxida tive deamination of some AA (  H 2 O 2 ) </li></ul><ul><li>desaturation deamination of histidine  urocanic acid + NH 3 </li></ul><ul><li>oxidative deamination of terminal –NH 2 in lysine lysyl oxidase(Cu 2+ ): Lys + O 2  NH 3 + allysine + H 2 O </li></ul><ul><li>dehydratation deamination of serine (see next lecture) </li></ul><ul><li>oxida tive deamination of biogenous amines, MAO monoamine oxidase (  H 2 O 2 , see also Med. Chem. II, p. 60 ) </li></ul>
  39. 39. Deamina tion of adenin e + NH 3 adenosin e monophosphate (AMP) inosin e monophosphate (IMP)
  40. 40. Oxida tive deamination of some A A uses flavin e c ofa c tor a nd di oxygen <ul><li>typic al for glycine </li></ul><ul><li>D-amino acids </li></ul><ul><li>side product is H 2 O 2 </li></ul>H 2 O + ½ O 2 2-imino acid catalase
  41. 41. Oxida tive deamination of biogenous amines R-COOH acid biogenous amine monoamine oxidase imine aldhyde
  42. 42. Desaturation type of deamination in histidine urocanic acid (urocanate)
  43. 43. Other reactions producing ammonia <ul><li>non-enzymatic carbamylation of proteins Prot-NH 2 + NH 2 -CO-NH 2  NH 3 + Prot-NH-CO-NH 2 </li></ul><ul><li>catabolism of pyrimidine bases cytosine/uracil  NH 3 + CO 2 + β -alanine thymine  NH 3 + CO 2 + β -aminoisobutyrate </li></ul><ul><li>synthesis of heme (4 porphobilinogen  4 NH 3 + uroporphyrinogen) </li></ul>
  44. 44. Hydrol ysis of amide group in glutamin e releases am monia (deamidation). In kidneys, NH 4 + ions are released into urine. glutam ate glutamin e glutaminase Glutamine is non-toxic transport form of ammonia
  45. 45. Ammonia production under pathological conditions <ul><li>bleeding in GIT  increased NH 3 in portal blood </li></ul><ul><li>uroinfections – bacterial urease catalyzes the hydrolysis of urea </li></ul>H 2 N-CO-NH 2 + H 2 O  2 NH 3 + CO 2 NH 3 + H 2 O  NH 4 + + OH - alkali ne urine (pH ~ 8)  phosphate stones
  46. 46. Acid e-base properties of NH 3 <ul><li>p K B (NH 3 ) = 4 . 75 ( weak base ) </li></ul><ul><li>NH 3 + H 2 O  NH 4 + + OH - </li></ul><ul><li>p K A (NH 4 + ) = 14 – 4 . 75 = 9 . 25 (v ery weak acid ) </li></ul>under physiological pH values in ICF and ECF ( ~ 7.40): 98 % NH 4 + 2 % NH 3
  47. 47. Compare: Ammonium ions in body fluids hydrolysis of Gln, deamination of Glu (tubules) hydrolysis of urea by oral microflora protein putrefaction (GIT), Gln/Glu catabolism (enterocyte) catabolism of AA in tissues 10 – 40 mmol/l 2 – 3 mmol/l 100 – 300 μ mol/l 5 – 30 μ mol/l Urine Saliva Portal blood Venous blood Metabolic origin of NH 4 + Concentration of NH 4 + ions Body fluid
  48. 48. <ul><li>Low-protein diet (especially important in liver diseases) </li></ul><ul><li>Alteration of colon microflora by the ingestion of: </li></ul><ul><li>Probiotics – live bacteria stimulating saccharolytic (fermentative) processes in large intestine instead of putrefactive ones ( L a c tobacil lus , Bifidobacterium ) – yoghurt, kefir milk etc. </li></ul><ul><li>Prebiotics – n on-digestible food ingredients (polysaccharides) that stimulate the growth probiotics in the colon (dietary fibre, inulin) </li></ul>How to decrease ammonia production in body?
  49. 49. Detoxification of ammonia
  50. 50. T hree ways of ammonia detoxication  α -amino acid hydrog. amin. 2-OG GMD 1 NADPH+H + mitochondri a (brain)     γ - amid e of Glu Glu + NH 3 Gln-synthetas e 1 ATP cytosol liver, brain , other       H 2 CO 3 diamide urea cy cle 5 enzym es 4 ATP mitoch. + cytosol only liver Relevance Compound type Rea ction(s) Enzym e Energ y needs Organelle(s) Org an(s) Glutam ate (Glu) Glutamin e (Gln) Urea Feature
  51. 51. Ureasynthesis in liver 5 reactions 1. + 2. mitochondria 3. - 5. cytosol
  52. 52. 1. Carbamoyl phosphate (matrix) <ul><li>carbamoyl phosphate synthetase I </li></ul><ul><li>matrix of mitochondria </li></ul><ul><li>two moles of ATP </li></ul><ul><li>amide bond + mixed anhydride </li></ul><ul><li>m acroergic compound </li></ul>
  53. 53. Carbamoyl is the acyl of c arbam ic acid carbamic acid carbonic acid monoamid e does not exist carbamoyl
  54. 54. 2. Citrulline formation (matrix) citrulline carbamoyl ornithine
  55. 55. 3. The second -NH 2 group comes from aspartate (cytosol) citruline aspartate argininosuccinate
  56. 56. Less usual hydrolysis of ATP means that two ATP are consumed ATP + H 2 O  A M P + P P i PP i + H 2 O  2 P i (diphosphatase, pyrophosphatase) AMP + ATP  2 ADP (adenylate kinase) -------------------------------------------------- summary: 2 ATP + 2 H 2 O  2 ADP + 2 P i
  57. 57. 4. The cleavage of argininosuccinate argininosuccinate arginine fumarate
  58. 58. 5. Hydrolysis of arginine affords urea arginine ornithine
  59. 59. M etabolic origin of nitrogen in urea free ammonia aspartate
  60. 60. Dual function of glutamate in AA catabolism glutamate + NAD +  ammonia + 2-OG + NADH+H + GMD UREA oxalacetate AST 2-oxoglutarate aspartate
  61. 61. Urea s ynt hesis is proton-produ ctive reaction CO 2 + NH 4 + + aspart ate  urea + fumar ate + H 2 O + 2 H + CO(NH 2 ) 2 + - OOC-CH=CH-COO - + H 2 O + 2 H + CO 2 + NH 4 + +
  62. 62. Urea is n on- ele c trolyt e <ul><li>carbonic acid diamide </li></ul><ul><li>pol ar compound (dip ole )  well soluble in water </li></ul><ul><li>diffuses easily through cell membranes (hydro philic pores ) </li></ul><ul><li>contributes to blood plasma osmolalit y </li></ul><ul><li>osmolalit y  2 [Na + ] + [glu c os e ] + [urea] mmol/kg H 2 O </li></ul><ul><li>synthesis only in liver </li></ul><ul><li>excretion by urine depends on the amount of food proteins </li></ul><ul><li>330-600 mmol/day (20-35 g/day) </li></ul>
  63. 63. Urea in blood serum (2-8 mmol/l) <ul><li>Increased concentration </li></ul><ul><li>renal failure </li></ul><ul><li>increased protein catabolism (sepsis, burns, polytrauma, fever etc.) </li></ul><ul><li>Decreased concentration </li></ul><ul><li>lack of proteins in diet </li></ul><ul><li>liver failure </li></ul>
  64. 64. Compare and distinguish urea × uric acid !
  65. 65. Compare liver and other tissues liver only Organe location cytosol mitochondria + cytosol Subcellular location 150 - 400 μ mol/l 2 - 8 mmol/l Serum concentration 0.5 - 1 g/day 20 - 35 g/day Urine excretion 1- 2 % 80 - 90 % Catabolic nitrogen 2,6,8-trihydroxypurin e acidum uricum weak diprotic acid p oor , depeds on pH yes  antioxidant yes (two types) a denin e and guanin e carbonic ac. diamid e urea non- ele c trolyt e excelent n o n o a mino acids Chemic al name Latin name In water Solubility in water Redu cing property Salt formation C atabolit e of Uric acid Urea Feature H
  66. 66. Glutamine synthesis glutamine synthetase glutamate glutamine 2. way of detoxification
  67. 67. In kidneys, ammonia is relased from glutamine and glutamate. Ammonium cation is excreted by mildly acidic urine urine (pH ~ 5) 2-oxo gluta rate glutaminase glutamate dehydrogenase
  68. 68. Multiple functions of glutamine <ul><li>Synthesis of proteins </li></ul><ul><li>Metabolic fuel – for some tissues: enterocytes, lymphocytes, macrophages, fibroblasts, kidneys </li></ul><ul><li>Source of nitrogen in synthesis – purine, pyrimidines, NAD + , aminosugars </li></ul><ul><li>Source of glutamate – glutathione ( GSH ) , GABA, Glu  ornithin e , Glu  prolin e </li></ul><ul><li>Source of ammonium ions in urine </li></ul><ul><li>detoxification of ammonia in tissues and non-toxic transport form of ammonia from tissues to liver </li></ul>!
  69. 69. Glutamate dehydrogenase reaction is reversible ammonia formation 3. way of ammonia detoxication of 2-oxoglutar ate amina tion h ydroge nation of glutam ate deamina tion d ehydrogena tion
  70. 70. Subcellular location of AA conversions t ransamination (ALT)  glutamate NH 3 glutamate synthesis of urea mitochondria cytosol GMD Glu + NH 3  Gln t ransamination (AST) cytosol
  71. 71. Synthesis of non-essencial amino acids
  72. 72. Synthesis of glycine 1. The reverse of transamination 2. From serine 2-oxoglutarate glutamate glyoxalate serine glycine
  73. 73. Formation of serine from the glycolysis intermediate glu c os e glycolysis 3-P-glycer ate 3-P-hydroxypyruv ate 3-P-serin e transamination
  74. 74. Synthesis of alanine from pyruvate and glutamate (ALT = alanine aminotransferase) alanine pyruvate glutamate 2-oxoglutarate
  75. 75. Aspartate from oxaloacetate and glutamate (AST = aspartate aminotransferase) AST reaction produces aspartate for urea synthesis aspartate glutamate 2-oxoglutarate oxaloacetate
  76. 76. Proline synthesis is the opposite of its catabolism proline glutamate 5-semialdehyde glutamate pyrroline-5-carboxylate oxidation addition of H 2 O ring opening
  77. 77. Glutamate is formed by the reductive amination of 2-oxoglutarate (GMD reaction) L-glutamate 2-iminoglutarate 2-oxoglutarate
  78. 78. Hydroxyla tion of essential ph enylalanin e gives non-essential tyrosine tetrahydrobiopterin e (BH 4 ) is a donor of 2H to form water from the second oxygen atom phenylalanine tyrosine
  79. 79. Glutamine from glutamate and ammonia glutamine synthetase glutamate glutamine Similarly: asparagine from aspartate
  80. 80. Cysteine is made from methionine methionine homocysteine cystathionine homoserine cysteine condensation with serine cysteine release
  81. 81. Selenocystein e arises c o - transla tionally from serine a nd seleno phosphate Ser yl -tRNA + selenophosphate  selenocyste yl -tRNA + phosphate Selenophosphate is made from selenid e ( food ) a nd ATP Se 2- + ATP + H 2 O  AMP + P i + few enzymes (redox reactions) contain selenocystein e Glutathione peroxidase (2 GSH + H 2 O 2  2 H 2 O + G-S-S-G) Deiodase of thyronines (thyroxine T4  triiodothyronine T3) Thioredoxin reductase (ribose  deoxyribose)

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