03 Protein Metabolism
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Transcript of 03 Protein Metabolism
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Protein Metabolism
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Use of Amino Acids Blood
Tissue protein synthesis
Synthesis of metabolites Enzymes, hormones
Deamination or transamination
Enterocyte Uses amino acids for own needs
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The Gut... Fastest growing organ
immediately after birth or hatch
Approximately 5% of BW Accounts for:
20% of resting whole-body O2
consumption Active transport mechanisms for nutrients
45% of whole-body protein synthesis
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In the Enterocytes First cells that can use
dietary amino acidsTransport into portal
blood
Protein synthesis Digestive enzymes Structure and growth
Energy
Stoll et al. (1998)
%
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Enterocyte Use of Amino
Acids Energy
Primarily glutamine
Synthesize compounds Apoproteins for lipoprotein formation
Digestive enzymes
Hormones
Other nitrogen-containing compounds
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m no cUtilization
Amino Acids and Peptides in SmallIntestine
EnterocyteEnergy andSynthesis ofCompounds
Free Amino
Acids
Liver
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Fate of Absorbed Amino
AcidsThree categories
Tissue protein synthesis
Synthesis of enzymes, hormones, andother metabolites
Deamination or transamination
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Protein Transport in the
Blood Amino acids diffuse across the
basolateral membrane
Enterocytesportal blood liver tissues Transported mostly as free amino acids
Liver Potential breakdown of many amino acids
As needed
Synthesis of non-essential amino acids
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Protein Metabolism in Cells Transport of amino acids from blood into cells
tRNA immediately picks up amino acid
DNA
Replication
Protein
AAAAAAAA
Translation
mRNA
Transcription
tRNA
AA
AA
AAAA
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Protein Metabolism in Cells No storage of amino acids in cells
Synthesis of functional proteins
Proteins degraded to free aminoacids Amino acid concentration in blood
is fairly constant
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Synthesis
Degradation
Constant Turnover of
Proteins Degradation and re-synthesis of protein
Some amino acids are degradedand must be replaced through the diet
Obligatory losses Growth requires that
synthesis > degradation
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Protein Synthesis On-going, semicontinuous activity in all
cells but rate varies greatly between
tissues Rate is regulated by hormones and
supply of amino acids and energy
Energetically expensive requires about 5 ATP per one peptide bond
Accounts for about 20% of whole-bodyenergy expenditure
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Rate of Protein SynthesisFraction of tissue proteinsynthesized per day (%/d)
Tissue Pig Steer Liver
Gut
Muscle
23
45
5
21
39
2Muscle is far less metabolically active sorequires fewer cells to be replaced daily
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Hormonal Regulation Insulin
Glucose availability to cells increases
Protein synthesis increases
Glucagon Protein synthesis decreases
Protein degradation increases
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Protein Synthesis Protein synthesis of any particular
protein cannot proceed without an
adequate supply ofall amino acidsthat will contribute to the primarystructure of that specific protein
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Glutamine + ketoacid
Glutamate + amino acid
H|OOCCNH3
+ OOCC=O| |R R
Amino acid Ketoacid
ro e n e a o sm nCells
All 20 amino acids must be present If not, must be synthesized in liver
Synthesis of non-essential amino
acidsTransamination: Transfer of NH
2-group
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Biosynthesis of
Nonessential Amino AcidsTransamination reactions
Allow extensive interconversion
between nonessential amino acids Requires vitamin B
6as a coenzyme
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Transamination Transfer of amino group from an amino
acid to an -keto acid
Used to synthesize amino acids asneeded Some essential amino acids
Not lysine or threonine
Must have appropriate -keto acid in diet
Requires vitamin B6 in coenzyme form Pyridoxal phosphate (PLP)
Catalyzed by amino transferases
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Transamination
-Keto Acid
amin
o
Amino Acid
-Keto Acid
-Keto Acid
-Keto Acid
amino
-AminoAcid
PLPAminotransferase
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n
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Amino Acid
Interrelationships Methionine can be converted to Cys
If too little Cys in diet, Met is converted to Cysand Met becomes deficient Up to 50% of Cys requirement met through Met
Phe can be converted to Tyr Requirement is typically stated for Phe + Tyr
CC
H
O
O
NH3+
C
H2
CC
H
O
O
NH3+
C
H2
HO
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Protein Catabolism Occurs when
Dietary protein exceeds protein
requirements of body Normal situation in true carnivores Abnormal in omnivores and herbivores
Composition of absorbed amino acidsis unbalanced
Gluconeogenesis is increased
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Protein Catabolism Some net catabolism of body
proteins occurs at all times Expressed as urinary nitrogen
excretion Use the carbon backbone for energy,
excrete the nitrogen as urea
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Urinary Nitrogen Excretion
Urine
KIDNEY
LIVER
Urea
Urea
CO2
Amino acids keto acids
NH3
Blood
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Deamination Removal of amino group from an
amino acid with no transfer
Produces ammonia and -keto acid Ammonia removed by urea cycle
-keto acid is metabolized via several
potential pathways Pyridoxal phosphate (PLP) required
(B6)
eam na o
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eam na ona
m
ino
-Keto Acid
DehydratasePLP
H2O
-Keto Acid + NH4
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Keto acids can Enter the TCA cycle and be broken down to
CO2 and H2O with release of energy Be used for gluconeogenesis
Some, not all amino acids In liver (and kidney)
Lipogenesis (fatty acid biosynthesis) Ketogenesis
Ketone bodies (acetoacetate, acetyl-CoA) Used as energy source in various tissues
Use of Keto Acids for
Energy
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Ketogenic Amino Acids Leucine and isoleucine
Converted to acetoacetate or acetyl
CoA in liver Fuel for other tissues
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Use of Amino Acids for
Energy Not economical
Energy feeds are less expensive (per kcal) thanprotein feeds
Item CP ME ME Cost Cost
% Mcal/kg Mcal/ton $/ton /Mcal Corn 8 3.42 3,102 71.4 2.30
SBM 48 3.38 3,066 150.0 4.89
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Disposal of NH3
NH3 is very toxic and must be
detoxified and excreted from the body Fish: NH3 Mammals: Urea Birds: Uric acid
Synthesis of uric acid Same pathway as for purines
Synthesis of ureathe urea cycle Detoxifies NH3 to urea
Synthesizes arginine
UREA
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Essential
Amino Acids Amino acids that can become essential in
certain physiologic conditions Example: taurine in cats
Example: proline in young pigs
Example: tyrosine becomes essential in peoplewith phenylketonuria (PKU) PKU; 1 in 15,000 babies
Hydroxylation of phenylalanine normally forms tyrosine Tyrosine important in adrenaline, noradrenaline, thyroxine
and melanin synthesis
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Phenylketonuria (PKU) Normal situation:
Phenylalanine
(essential aa)
Tyrosine
(nonessential aa)
In PKU: Phenylalanine builds up
Can cause mental retardation
Condition inherited from parents(genetic)Phenylalanine
(essential aa)
Tyrosine
(nonessential aa)
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PKU Symptoms VERY FEW symptoms if diagnosed early and diet strictly
regulated IF NOT:
Lighter skin, hair and eyes than siblings Phenylalanine important in synthesis of melanin
Delayed mental and social skills Head size significantly below normal Hyperactivity Jerking movements of the arms or legs Mental retardation (severe if not diagnosed and treated early) Seizures Skin rashes Tremors Unusual positioning of hands
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PKU Treatment EXTREMELY low phenylalanine intake
Diet for life Special low-phenylalanine infant formula
Used for life
Low or no milk, eggs No aspartame (NutraSweet) Fish oil supplements
Hard to get enough essential fatty acids on lowphenylalanine diet
Iron supplements
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