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PROTEIN METABOLISM

PROTEIN METABOLISM. Kadek Rachmawati. PROTEIN METABOLISM. Protein Catabolism Amino Acids Metabolism Amino Acids Catabolism Amino Acids Biosynthesis Specialized Products Protein Anabolism Replication Transcription Translation. Metabolism =  Catabolism + Anabolism .

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PROTEIN METABOLISM

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  1. PROTEIN METABOLISM Kadek Rachmawati

  2. PROTEIN METABOLISM • Protein Catabolism • Amino Acids Metabolism • Amino Acids Catabolism • Amino Acids Biosynthesis • Specialized Products • Protein Anabolism • Replication • Transcription • Translation

  3. Metabolism = Catabolism + Anabolism  • Metabolism consists of catabolism and anabolism • Catabolism: degradative pathways • Usually energy-yielding! • Anabolism: biosynthetic pathways • energy-requiring!

  4. THE FUNCTION OF PROTEIN • ENZYME • HORMONE • TRANSPORT OF COMPOUND IN BLOOD • ACID-BASE BALANCE • WATER BALANCE • ANTIBODY • STRUCTURAL COMPONENT OF CELL

  5. Digestion • The process whereby nutritive substances , vitamins,minerals and fluids enter the body. • Proteins are broken down to absorbable units • The passage across the intestinal wall is absorption

  6. PROTEIN DIGESTION

  7. PROTEIN DIGESTION AND ABSORBTION

  8. NITROGEN BALANCE • Nitrogen balance = nitrogen ingested - nitrogen excreted (primarily as protein) (primarily as urea) • Nitrogen balance = 0 (nitrogen equilibrium) protein synthesis = protein degradation • Positive nitrogen balance protein synthesis > protein degradation • Negative nitrogen balance protein synthesis < protein degradation

  9. Amino Acid Metabolism Metabolism of the 20 common aminoacids is  considered from the origins and fates of their:   (1) Nitrogen atoms   (2) Carbon skeletons

  10. AMINO ACIDS METABOLISM • Amino Acids Metabolism • Amino Acids Catabolism • Nitrogen atoms catabolism • Transamination reactions • Oxidative deamination reactions • NH3 production and Transport • Urea cycle and disorders • Carbon skeletons catabolism • Amino Acids Biosynthesis • Specialized Product

  11. Three sources of amino acids for degradation in animals :  • During normal synthesis and breakdown of proteins, some amino acids are no longer needed. • When diet exceeds the body’s need for amino acids. • Proteins can be degraded and used as fuel to maintain the organism.

  12. NITROGEN ATOMS CATABOLISM • Transamination reactions • Oxidative Deamination reactions • Amonia (NH3) production and transport • Urea cycle

  13. The different forms of excreted nitrogen • •Ureotelic (mammals) : urea • •Uricotelic (birds, reptiles) : uric acid • •Ammonotelic (fish) : ammonia

  14. AMINO ACIDS DEGRADATION :

  15. Transamination Reactions  • Often the first step of aminoacid degradation Transfer of amino group from many amino acids to limited number of keto acid acceptors • Pyruvate <-> alanine • Alpha-keto-glutarate <-> glutamate • Transamination reactions tend to channel amino groups on to glutamate • Glutamate’s central role in aminoacid N metabolism

  16. alpha ketoglutarat NH3 CO2 Amino Acids Alphaketo acid L-Glutamat Urea TRANSAMINATION REACTIONS

  17. R-CH-NH2 R*-C=O | | HOOC HOOC R-C=O R*-CH-NH2 | | HOOC HOOC

  18. TRANSAMINATION

  19. TRANSAMINASE • ENZYME : 1. alanin transferase (alanin-piruvat transaminase) 2. glutamat transaminase (glutamat-alfa ketoglutarat transaminase) COENZYME : Piridoksal fosfat

  20. Deamination Reactions  ENZYME : • Glutamate dehydrogenase • Releases ammonia for urea synthesis • It is one of the few enzymes that can use NAD+ or NADP+ as e- acceptor.    • Enzyme inhibitor : ATP, GTP, NADH • Enzyme activator : ADP, GDP • Enzyme for regulator nitrogen atoms catabolism

  21. AMMONIA TRANSPORT TISSUE Hepar MUSCLE Amino acid NH4+ -KG Glu Ala Pyr Glucose GutamateUrea NH4+ Glutaminase H2O Glutamines Glu-KG Pyr Ala Glucose Glutamat NH4+ ATP H2O ADP, Pi Glutamines Glutamat dehydrogenase Glutamine sintetase GLUCOSE- ALANIN CYCLE

  22. O O C- NH2 C - OH CH2 CH2 CH2 CH2 H -C- NH2 H - C- NH2 COOH COOH Glutamin Glutamat

  23. Detoxification of Ammonia by the Liver: the Urea Cycle  • Aminoacid flow from muscle to liver • Transfers N to urea • Liver very effective at eliminating ammonia from blood

  24. Urea Cycle • Enzymes in mitochondria: • 1. Ornithine Transcarbamoylase • Enzymes in cytosol: • 2. Arginino-Succinate Synthetase • 3. Arginino-succinase • 4. Arginase.

  25. UREA FORMATION

  26. Urea Formation • Occurs primarily in liver; excreted by kidney • Principal method for removing ammonia • Hyperammonemia: Defects in urea cycle enzymes (CPS, OTC, etc.) • Severe neurological defects in neonates Treatment: • Stop protein intake • Dialysis • Increase ammonia excretion: Na benzoate etc.

  27. UREA CYCLE :

  28. UREA CYCLE DISORDERS Hereditary deficiency of any of the Urea Cycle enzymes leads to hyperammonemia - elevated [ammonia] in blood. Total lack of any Urea Cycle enzyme is lethal. Elevated ammonia is toxic, especially to the brain. If not treated immediately after birth, severe mental retardation results.

  29. DISORDERS OF UREA CYCLE : UCD Enzyme deficiency • Hyperammonaemia type I 1 • Hyperammonaemia type II 2 • Citrulinemia 3 • Arginino succinat aciduria 4 • Hyperargininaemia 5

  30. Resolution of Clinical Case: Genetics • Gene for OTC found on X-chromosome • Women are carriers • usually asymptomatic • may experience migraines, vomiting, lethargy when eating high protein meals (meat) • OTC deficiency most common (but rare) disorders of the urea cycle (1: 20-80,000)

  31. CARBON SKELETONS CATABOLISM

  32. AMINO ACIDS Glycogenic Ketogenic Mixed ala hip leu ileu arg met ly asp pro fen sis ser tir glu treo trip gli val his

  33. Ala ser Cys thr Gly trp hyp Ile Leu Trp glu Arg His Gln pro pir Asetil koA Asetoasetil KoA asp asn Ile Met val Trp Tyr Leu Lis phe hil tir phe tir sis

  34. CARBON SKELETONS CATABOLISM

  35. CARBON SKELETONS CATABOLISM DISORDERS : Disease Amino Acid • Glisinuria glisin Hiperoksaluria primer • Fenilketonuria fenilalanin • Tirosinosis,Tirosinemia, tirosin Alkaptonuria • Histidinemia,Imidazol- histidin aminoaciduria • Prolinemia,Hidroksiprolin- prolin,hip emia

  36. Disease Amino Acid • Hiperlisinemia,Hiper- lisin lisinemia persisten • Sistinuria,Sistinosis, sistein, metionin Homosistinuria • Hipervalinemia,Maple leusin,valin, syrup urine disease, isoleusin Intermitent branched chain ketonuria,Isovale- ricacidemia

  37. Disease Amino Acid • Hartnup`s disease triptofan

  38. For mammals: • Essential amino acids must be obtained from diet Nonessential amino acids - can be synthesized

  39. AMINO ACIDS BIOSYNTHESIS

  40. AMINO ACIDS BIOSYNTHESIS

  41. SPECIALIZED PRODUCTS :

  42. PROTEIN SYNTHESIS

  43. PROTEIN METABOLISM • PROTEIN SYNTHESIS • Replication • Transcription • Translation • Initiation • Elongation • Termination • Antibiotics in synthesis protein process

  44. NUCLEIC ACID : Polymer nucleotides Component : sugar nitrogen base phosphate

  45. D-ribosa D-2-deoxyribosa

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