dr. azin nowrouzi tehran university of medical sciences dr. azin nowrouzi tehran university of...
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Dr. Azin NowrouziTehran University of Medical SciencesDr. Azin NowrouziTehran University of Medical Sciences
TUMS
Major Functions of NitrogenMajor Functions of NitrogenDerived from Dietary ProteinDerived from Dietary ProteinMajor Functions of NitrogenMajor Functions of NitrogenDerived from Dietary ProteinDerived from Dietary Protein
Heme Blood cell
Choline PL
Glycosamine Sugar
Nucleotides DNA
Protein synthesis
Protein
Biogenic amines Neurotransmitters
Carnitine Heart
Creatine phosphate
« Energy »
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The nitrogen cycle
The nitrogen cycle
• No biomolecules are dedicated to the storage of N
• excess N is excreted
• N must be replenished by dietary protein 4
A. Ammonia Is Incorporated into
Glutamate
A. Ammonia Is Incorporated into
Glutamate• Reductive amination of -ketoglutarate by glutamate dehydrogenase occurs in plants, animals and microorganisms
• In mammals & plants, located in mitochondria.
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B. Glutamine Is a Nitrogen Carrier in Many Biosynthetic
Reactions
B. Glutamine Is a Nitrogen Carrier in Many Biosynthetic
Reactions• A second important route in assimilation of ammonia is via glutamine synthetase
• It is present in all organisms.
• In humans it is most active in the liver.
• Glutamine is transported from the liver to other tissues via the blood.
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• Glutamate synthatase is not present in humans.• It is found in Bacteria• It is used by blue-green algae and by Rhisobia.
Glutamate synthetaseGlutamate synthetase
TransaminationReversible transfer of Ammonia between amino acids and -ketoacids
by aminotransferase
TransaminationReversible transfer of Ammonia between amino acids and -ketoacids
by aminotransferase• Glutamate provides the amino group for
the synthesis of many • other amino acids through trasamination
reactions
Prosthetic group involved in amino transfer 9
Central role of the aminotrasferases and glutamate dehydrogenase in nitrogen metabolism
Central role of the aminotrasferases and glutamate dehydrogenase in nitrogen metabolism
1. Proteins are degraded to amino acids
2. Removal of nitrogen is first step in degradation
3. Ammonium is converted into urea
4. C-skeleton enters known pathways
5. Amino acids are made from intermediates of other pathways
Amino Acid SynthesisAmino Acid Synthesis• The ability of an organism to live and grow is dependent on
protein synthesis• Therefore, a supply of all 20 aa is necessary.• Higher plants are able to synthesize all 20 aas.• Many microorganisms and higher animals make fewer• Humans make 10 of the 20 aas (these are called nonessential
amino acids.• The remainder must be supplied in the diet, usually in the
form of plant or animal proteins (these are called essential amino acids).
• All 20 amino acids are essential for life,• They are necessary for protein synthesis
– Essential or indispensable: 9– Nonessential or dispensable: 11
• Review complete vs. incomplete• All natural, unprocessed animal and
plant foods contain all twenty amino acids
• A lack of any one of them leads to severe metabolic disruption and ultimate death.
• All 20 amino acids are essential for life,• They are necessary for protein synthesis
– Essential or indispensable: 9– Nonessential or dispensable: 11
• Review complete vs. incomplete• All natural, unprocessed animal and
plant foods contain all twenty amino acids
• A lack of any one of them leads to severe metabolic disruption and ultimate death.
Metabolic Classification of the Amino Acids
Metabolic Classification of the Amino Acids
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• Their synthesis depends on the availability of the appropriate carbon skeletons and a source of ammonia.
• Glucose is ultimately the source of carbon skeletons for most nonessential aa.
• Two essential aa, phenylalanine and methionine, are used to make tyrosine and cysteine, respectively.
• Since ammonia is available in the fed state, amino acids become essential to our diet when we are not able to synthesize their carbon skeletons.
What are the nonessential amino acids synthesized from?
What are the nonessential amino acids synthesized from?
α-keto acids required for synthesis of nonessential amino acids
α-keto acids required for synthesis of nonessential amino acids
α-keto acid Amino acid
PyruvateOxaloacetateα-keto glutaratePyruvate, 3-phosphoglycerate
AlanineAspartate, AsparagineGlutamate, glutamine, Proline, ArginineSerine
Amino acids are precursors of some other biomolecules
Amino acids are precursors of some other biomolecules
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Protein QualityAnimal vs. Plant protein
Protein QualityAnimal vs. Plant protein
• Important in maintaining N balance• Proteins have different biological value (BV)• Major reasons why animal protein is called BV protein,
whereas plant protein is of lower BV:– Animal protein is “complete” - contains all essential amino acids– Contains essential amino acids in larger amounts and in proper
proportion for optimal utilization • Note: Soybean protein even though from a plant, is
comparable to animal proteino In children leads to kwashiorker
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NoteNote
• The 56-g protein requirement for adult male can be met by 45 g of animal protein
• Same requirement would necessitate 65 g plant protein
• Combining plant products (legumes + grains) provides all essential amino acids
• Mixture of 30% animal protein and 70 % plant protein similar to use of animal protein alone
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Protein RDA varies in different stages of life cycle
Protein RDA varies in different stages of life cycle
• 0-0.5 years: 1 g/lb• 0.5-1 years: .71 g/lb• 1-6 years: .56 g/lb• 7-14 years: .45 g/lb• 15-18 years: .41 g/lb• 19+ years: .36 g/lb• 1Ib = 0.4536 kg
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Protein TurnoverProtein Turnover
• Body proteins turn over; t1/2= min - wks
• 400g of protein are synthesized per day and 400g are broken down– Secretory proteins such as digestive enzymes,
polypeptide hormones, and antibodies, turn over rapidly
– Structural proteins are much more metabolically stable.
Chemical Signals for Turnover
Chemical Signals for Turnover
• ubiquitinatin– A small, heat stable protein (ubiquitin) reacts with
other proteins to mark them for destruction
• Oxidation of amino acid resides- Pro, Arg, Lys• Pest sequences- one or more regions rich in
proline (P), gltamate (E),serine (S), and threonine (T)
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Protein DigestionProtein Digestion
• Gastric Digestion– Function of pH
• Kills bacteria• Denatures
proteins…
– Activation and Action of Pepsin
• Intestinal Digestion– Pancreatic
enzymes– Intestinal enzymes 30
Activation of the Gastric and Pancreatic Zymogens
Activation of the Gastric and Pancreatic Zymogens
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Trypsinogen
Val-Asp-Asp-Asp-Asp-Lys
TrypsinProelastase
Elastase
Procarboxypeptidase
Carboxypeptidase
Chymotrypsinogen
Chymotrypsin
Enteropeptidase
slow, nonenzymatic
pepsinogen(zymogen)
fast, enzymatic
pepsin
+
autocatalyticconversion of
pepsinogen to pepsin
denaturedproteins hydrolysis
large peptidefragments 33
Zymogens ActivationZymogens Activation
di- and tripeptides aa's
di- and tripeptides
amino acids
peptidases
amino-peptidase
Brush Border
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Final conversion of peptides to free amino
acids
Final conversion of peptides to free amino
acids
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• Secondary active transport driven by Na+ gradient
• Facilitated diffusion
Amino Acid AbsorptionAmino Acid Absorption
Na+
Na+
ATPADP Na+
K+
K+
Intestinallumen Amino
acid Brush border
Active transporter
Aminoacid +Pi
Facilitatedtransporter
Amino acid
Serosalside
Portal vein
Di- andTripeptides
peptidasespeptides
Transepithelial amino acid transport.
Na+
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Gamma-Glutamyl CycleGamma-Glutamyl Cycle
• A metabolic cycle for transporting amino acids into cells.
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Disorders of Amino Acid transportation or absorption
Disorders of Amino Acid transportation or absorption
Uptake (transport) systems exist especially in intestine & kidney. Lack of specific transporter results in a disease state.This can be partially overcome through uptake of peptides.
Uptake (transport) systems exist especially in intestine & kidney. Lack of specific transporter results in a disease state.This can be partially overcome through uptake of peptides. 40