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 

Metabolism consists of catabolism and anabolism

Catabolism: degradative pathways Usually energy-yielding!

Anabolism: biosynthetic pathways energy-requiring!

THE FUNCTION OF PROTEIN

ENZYME HORMONE TRANSPORT OF COMPOUND IN

BLOOD ACID-BASE BALANCE WATER BALANCE ANTIBODY STRUCTURAL COMPONENT OF CELL

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

PROTEIN DIGESTION

PROTEIN DIGESTION AND ABSORBTION

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

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

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

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.

NITROGEN ATOMS CATABOLISM

Transamination reactions Oxidative Deamination reactions Amonia (NH3) production and transport Urea cycle

The different forms of excreted nitrogen

•Ureotelic (mammals) : urea

•Uricotelic (birds, reptiles) : uric acid

  •Ammonotelic (fish) : ammonia

AMINO ACIDS DEGRADATION :

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

TRANSAMINATION REACTIONS

Amino AcidsAmino Acids alpha ketoglutaratalpha ketoglutarat CO2CO2

Alphaketo acidAlphaketo acid L-GlutamatL-Glutamat UreaUrea

NH3NH3

R-CH-NH2 R*-C=O

| |

HOOC HOOC

R-C=O R*-CH-NH2

| |

HOOC HOOC

TRANSAMINATION

TRANSAMINASE ENZYME :

1. alanin transferase (alanin-piruvat

transaminase)

2. glutamat transaminase (glutamat-alfa

ketoglutarat transaminase)

COENZYME :

Piridoksal fosfat

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

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

O O

C- NH2 C - OH

CH2 CH2

CH2 CH2

H -C- NH2 H - C- NH2

COOH COOH

Glutamin Glutamat

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

Urea Cycle

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

UREA FORMATION

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.

UREA CYCLE :

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

DISORDERS OF UREA CYCLE :

UCD Enzyme deficiency

Hyperammonaemia type I 1 Hyperammonaemia type II 2 Citrulinemia

3 Arginino succinat aciduria 4 Hyperargininaemia 5

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)

CARBON SKELETONS CATABOLISM

AMINO ACIDS

Glycogenic Ketogenic Mixed

ala hip leu ileu

arg met ly

asp pro fen

sis ser tir

glu treo trip

gli val

his

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

CARBON SKELETONS CATABOLISM

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 :

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

Disease Amino Acid

Hartnup`s disease triptofan

For mammals:

Essential amino acids must be obtained from diet Nonessential amino acids - can be synthesized

AMINO ACIDS BIOSYNTHESIS

AMINO ACIDS BIOSYNTHESIS

SPECIALIZED PRODUCTS :

PROTEIN SYNTHESIS

PROTEIN METABOLISM PROTEIN SYNTHESIS

Replication Transcription Translation

Initiation Elongation Termination Antibiotics in synthesis protein process

NUCLEIC ACID :

Polymer nucleotides Component : sugar

nitrogen base

phosphate

D-ribosa D-2-deoxyribosa

NITROGEN BASE :PURIN PYRIMIDIN

PURIN :

PYRIMIDIN :

CYTOSINE URACIL THYMINE

DNA Composition :

Purines:       Adenine A         Guanine G 

Pyrimidines:

      Thymine T  Cytosine C 

RNA Composition :

Purines:        Adenine A         Guanine G   

Pyrimidines:        Uracil U                    Cytosine C 

NUCLEOTIDES STRUCTURE:

POLYNUCLEOTIDES STRUCTURE

DNA STRUCTURE :

Genetic Code :

Initiation :

Initiation Codon :

Termination Codon :

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)

Antibiotics - Translation