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PROTEIN METABOLISM Kadek Rachmawati
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PROTEIN METABOLISM Protein Catabolism Protein Anabolism
Amino Acids Metabolism Amino Acids Catabolism Amino Acids Biosynthesis Specialized Products Protein Anabolism Replication Transcription Translation
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Metabolism = Catabolism + Anabolism
Metabolism consists of catabolism and anabolism Catabolism: degradative pathways Usually energy-yielding! Anabolism: biosynthetic pathways energy-requiring!
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THE FUNCTION OF PROTEIN
ENZYME HORMONE TRANSPORT OF COMPOUND IN BLOOD ACID-BASE BALANCE WATER BALANCE ANTIBODY STRUCTURAL COMPONENT OF CELL
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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
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PROTEIN DIGESTION
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PROTEIN DIGESTION AND ABSORBTION
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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
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Amino Acid Metabolism Metabolism of the 20 common amino acids is considered from the origins and fates of their: (1) Nitrogen atoms (2) Carbon skeletons
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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
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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.
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NITROGEN ATOMS CATABOLISM
Transamination reactions Oxidative Deamination reactions Amonia (NH3) production and transport Urea cycle
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The different forms of excreted nitrogen
•Ureotelic (mammals) : urea •Uricotelic (birds, reptiles) : uric acid •Ammonotelic (fish) : ammonia
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AMINO ACIDS DEGRADATION :
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Transamination Reactions
Often the first step of amino acid 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 amino acid N metabolism
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TRANSAMINATION REACTIONS
Amino Acids alpha ketoglutarat NH3 CO2 Alphaketo acid L-Glutamat Urea
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R-CH-NH2 R*-C=O | | HOOC HOOC R-C=O R*-CH-NH2 | | HOOC HOOC
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TRANSAMINATION
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TRANSAMINASE ENZYME : 1. alanin transferase (alanin-piruvat
2. glutamat transaminase (glutamat-alfa ketoglutarat transaminase) COENZYME : Piridoksal fosfat
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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
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AMMONIA TRANSPORT TISSUE NH4+ Glutaminase Hepar MUSCLE Amino acid NH4+
-KG Glu Ala Pyr Glucose Glutamat NH4+ ATP H2O ADP, Pi Glutamines Gutamate Urea NH4+ Glutaminase H2O Glutamines Glu -KG Pyr Ala Glucose Glutamat dehydrogenase Glutamine sintetase GLUCOSE- ALANIN CYCLE
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O O C- NH2 C - OH CH2 CH2 H -C- NH2 H - C- NH2 COOH COOH Glutamin Glutamat
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Detoxification of Ammonia by the Liver: the Urea Cycle
Amino acid flow from muscle to liver Transfers N to urea Liver very effective at eliminating ammonia from blood
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Urea Cycle Enzymes in mitochondria: 1. Ornithine Transcarbamoylase
Enzymes in cytosol: 2. Arginino-Succinate Synthetase 3. Arginino-succinase 4. Arginase.
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UREA FORMATION
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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.
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UREA CYCLE :
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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.
![UREA CYCLE DISORDERS Hereditary deficiency of any of the Urea Cycle enzymes leads to hyperammonemia - elevated [ammonia] in blood.](http://slideplayer.com./slide/6460891/22/images/30/UREA+CYCLE+DISORDERS+Hereditary+deficiency+of+any+of+the+Urea+Cycle+enzymes+leads+to+hyperammonemia+-+elevated+%5Bammonia%5D+in+blood..jpg "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.")
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DISORDERS OF UREA CYCLE :
UCD Enzyme deficiency Hyperammonaemia type I Hyperammonaemia type II Citrulinemia Arginino succinat aciduria Hyperargininaemia
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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)
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CARBON SKELETONS CATABOLISM
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AMINO ACIDS Glycogenic Ketogenic Mixed ala hip leu ileu arg met ly
asp pro fen sis ser tir glu treo trip gli val his
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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
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CARBON SKELETONS CATABOLISM
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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
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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
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Disease Amino Acid Hartnup`s disease triptofan
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For mammals: Essential amino acids must be obtained from diet Nonessential amino acids - can be synthesized
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AMINO ACIDS BIOSYNTHESIS
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AMINO ACIDS BIOSYNTHESIS
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SPECIALIZED PRODUCTS :
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PROTEIN SYNTHESIS
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PROTEIN METABOLISM PROTEIN SYNTHESIS Replication Transcription
Translation Initiation Elongation Termination Antibiotics in synthesis protein process
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NUCLEIC ACID : Polymer nucleotides Component : sugar nitrogen base
phosphate
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D-ribosa D-2-deoxyribosa
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NITROGEN BASE : PURIN PYRIMIDIN
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PURIN :
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PYRIMIDIN :
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CYTOSINE URACIL THYMINE
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DNA Composition : Purines: Adenine A Guanine G
Pyrimidines: Thymine T Cytosine C
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RNA Composition : Purines: Adenine A Guanine G
Pyrimidines: Uracil U Cytosine C
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NUCLEOTIDES STRUCTURE:
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POLYNUCLEOTIDES STRUCTURE
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DNA STRUCTURE :
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Genetic Code :
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Initiation :
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Initiation Codon :
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Termination Codon :
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POST TRANSLASI MODIFICATIONS (Pematangan protein) :
Fosforilation Metilation Asilation Sulfatation Glycosilation Bound with lipid Primary, secondary,tertiary dan quarternar structure of protein Protein folding 3D structure(konformation)
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Antibiotics - Translation
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