protein metabolism
DESCRIPTION
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 . - PowerPoint PPT PresentationTRANSCRIPT
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PROTEIN METABOLISM
Kadek Rachmawati
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PROTEIN METABOLISM
Protein Catabolism 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 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 AcidsAmino Acids alpha ketoglutaratalpha ketoglutarat CO2CO2
Alphaketo acidAlphaketo acid L-GlutamatL-Glutamat UreaUrea
NH3NH3
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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
transaminase)
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 Hepar MUSCLE
Gutamate Urea
NH4+
Glutaminase
H2O
Glutamines Glu -KG
Pyr Ala
Glucose
Glutamat NH4+
ATP
H2O
ADP, Pi
Glutamines
Glutamine
sintetase
Amino acid
NH4+
-KG Glu
Ala Pyr
Glucose
Glutamat dehydrogenase
GLUCOSE- ALANIN CYCLE
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O O
C- NH2 C - OH
CH2 CH2
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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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
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DISORDERS OF UREA CYCLE :
UCD Enzyme deficiency
Hyperammonaemia type I 1 Hyperammonaemia type II 2 Citrulinemia
3 Arginino succinat aciduria 4 Hyperargininaemia 5
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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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Alfaketoglutarat
oksaloasetat
sitrat
Suksinil koA
fumarat
glu Arg
His
Gln
pro
Ile
Met
val
Asetil koA
tir
phe
asp asn
Asetoasetil KoA
Leu
Lis
phe
Trp
Tyr
pir
Ala ser
Cys thr
Gly trp
hypIle
Leu
Trp
tir
hil
sis
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CARBON SKELETONS CATABOLISM
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Disease Amino Acid Glisinuria glisin
Hiperoksaluria primer Fenilketonuria fenilalanin Tirosinosis,Tirosinemia, tirosin
Alkaptonuria Histidinemia,Imidazol- histidin
aminoaciduria Prolinemia,Hidroksiprolin- prolin,hip
emia
CARBON SKELETONS CATABOLISM DISORDERS :
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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