03 protein metabolism

8/6/2019 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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03 protein metabolism

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