METABOLISME PROTEIN DAN ASAM AMINO
Evi Umayah Ulfa
TOPIK BAHASAN
Pencernaanprotein danpenyerapanasam amino
Siklus UreaBiosintesis
Asam Amino Non Esensial
MetabolismeNukleotida
Proteins and Amino Acids
• Essential – must be consumed in the diet
• Nonessential – can be synthesized in the body
Source of Amino Acids
Amino Acid Absorption
• Amino acids are absorbed in the small intestine
• Amino acids are transported to the liver from the intestines via the portal vein
• In the liver, amino acids are
– Used to synthesize new proteins
– Converted to energy, glucose, or fat
– Released to the bloodstream and transported to cells throughout the body
• Occasionally proteins are absorbed intact
Amino acid Catabolism
• Amino acids cannot be stored.
• If there is an excess of amino acids or a lack of other energy sources, the body will use them for energy production.
Amino acid degradation requires the removal of the amino group as ammonium.
• Ammonium must then be disposed of as it is toxic to the body.
How Much Protein?
• A 70 kg person (154 lb) typically consumes 100 g protein per day (dietary protein)
• To stay in nitrogen balance that person must excrete 100 g of N products per day
• The body makes 400 g of protein per day and 400 g are broken down into amino acids (body protein)
• 300 g of amino acids recycled into new protein, 100 g are degraded (urea cycle, glucose, ketone bodies)
• Total protein = 500 g/day, 400 g degraded, 400 resynthesized and 100 g catabolized
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
Nitrogen Balance and Imbalance
Figure 6.12
Dietary Protein…Digestion
Proteolytic Enzymes
Penyerapan AsamAmino
• Transpor aktif sekunder(dependen Na)
• Difusi terfasilitasi
• Siklus glutamil
Kotranspor Na dan Asam Amino
• Transport asam amino transepitel
• Lumen ke Vena portamelalui sel epitel
• Transporter : symporter– Na dan asam amino– Na dikeluarkan dari sel
epitel melalui transport aktifsedangkan asam amino masuk ke pembuluh darah(vena porta) melalui difusiterfasilitasi
Siklus Glutamil
Degradation of Body Protein (existing protein within the cells)
• All protein within the cells have the half life
( t1/2)
• Hemoglobin, muscle proteins, digestive enzymes, and the proteins of cells sloughed off from the gastrointestinal tract Extensive Synthesis and Degradation
• Two Mechanism :– lysosomes
– the ubiquitin/proteasome system
Protein Degradation
Ubiquitin/Proteasome Pathway
80-90%
Most intracellular proteins
• Lysosomal processes
10-20%
Extracellular proteins
Cell organelles
Some intracellular proteins
LYSOSOMES
Digestive System of the Cell
• Digests– ingested materials
– obsolete cell components
• Degrades macromolecules of all types– Proteins
– Nucleic acids
– Carbohydrates
– Lipids
• Heterogeneous
Lysosomal Enzymes
• 50 different degradative enzymes
• Acid hydrolases– Active at pH 5
(inside lysosome)– Inactive if released
into cytosol (pH 7.2)
• Acidic pH of lysosomes maintained by a proton
pump in the lysosomal membrane– Requires ATP, thus mitochondria
Different pathways lead to the lysosome1) Phagocytosis–Cell “eating” of material
> 250nm
2) Pinocytosis–Cell “drinking”
< 150nm
3) Receptor Mediated Endocytosis
-clathrin-coated pits
4) Autophagy–“self eat” of old worn out organelles, – important in cell degradation during apoptosis
Protein degradation in the lysosomes
Lysosomes degrade extracellular proteins that the cell incorporates by endocytosis.
Lysosomes can also degrade intracellular proteins that are enclosed in other membrane-limited organellas.
In well-nourished cells, lysosomal protein degradation is non-selective (non-regulated).
In starved cells, lysosomes degrade preferentially proteins containing a KFERQ “signal” peptide.
The regression of the uterus after childbirth is mediated largely by lysosomal protein degradation
The Ubiquitin/Proteasome
PATHWAY
UBIQUITIN
K
G
Small peptide that is a “TAG”
76 amino acids
C-terminal glycine - isopeptide
bond with the e-amino group of
lysine residues on the substrate
Attached as monoubiquitin or
polyubiquitin chains
Three genes in humans:
Two are stress genes (B and C)
One, UbA as a fusion protein
The 26S proteasome
Ubiquitinated proteins are degraded by the proteasome
Proteasomal protein degradation consumes ATP.
The proteasome degrades the proteins to ~8 amino-acid
peptides.
Access of proteins into the proteasome is tightly regulated.
The peptides resulting from the proteasome activity diffuse
out of the proteasome freely.
Ubiquitinated proteins are degraded in the cytoplasm and
nucleus by the proteasome.
The Ubiquitin/Proteasome Pathway
Four Main Steps:
UBIQUITINATION
RECOGNITION
DEGRADATION
DEUBIQUITINATION
NEURODEGENERATION
associated with
Alzheimer’s DiseaseParkinson’s Disease
Huntington’s DiseaseAmyotrophic Lateral Sclerosis
Parkinson’s Disease
Alzheimer’s Disease
Huntington’s Disease
Amyotrophic lateral
sclerosis
Spinocerebellar Ataxia
Disease
accumulation of
misfolded
proteins
Cell
Death
Neurodegenerative Disorders
Ubiquitin-Protein Aggregates
HUNTINGTON’S ALZHEIMER’S
PARKINSON’S LOU GEHRIG’S
f
PD: ubiquitin
c
AD: tau
d
AD: ubiquitin