Chapter 6
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Transcript of Chapter 6
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Chapter 6
Protein
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Functional Categories• Catalysts - enzymes
– Hydrolases - cleave compounds– Isomerases - transfer atoms in a
molecule– Ligases (synthases) - join compounds– Oxidoreductases - transfer electrons– Transferases - move functional
groups
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Functional Categories• Messengers
– Hormones• Structural elements
– Contractile proteins– Fibrous proteins– Globular proteins
• Immunoprotectors– Immunoproteins (antibodies)
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Functional Categories• Transporters
– Albumin– Transthyretin (prealbumin)– Transferrin– Ceruloplasmin– Lipoproteins
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Functional Categories• Buffers
– Regulation of acid-base balance• Fluid balancers
– Proteins attract water to blood• Other roles
– Adhesion, signaling, receptors, storage– Conjugated proteins
• Glycoproteins• Proteoglycans
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Protein Structure & Organization
• Primary structure– Sequence of covalent bonds among
amino acids• Secondary structure
– Hydrogen bonding -helix -conformation or -pleated sheet– Random coil
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Protein Structure & Organization
• Tertiary structure– Clustering of hydrophobic AAs toward center– Electrostatic (ionic) attraction– Strong covalent bonding between cysteine
residues - disulfide bridges• Quaternary structure
– Interactions between 2 or more polypeptide chains
– Oligomers
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Amino Acid Classification• Structure
– Central C– At least 1 amino group (NH2) – At least 1 carboxy (acid) group
(COOH)– Side chain (R group)
• Makes AA unique
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Amino Acid Classification• Net electrical charge
– Zwitterions have none• Polarity
– Polar or nonpolar– Determined by R group
• Essentiality– Lysine, threonine & histidine totally
indispensable
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Sources of Protein• Exogenous sources
– Animal products - except fats– Plant products - grains/grain products,
legumes, vegetables• Endogenous proteins
– Desquamated mucoasal cells– Digestive enzymes & glycoproteins
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Digestion & Absorption• Protein digestion
– Mouth & esophagus - none– Stomach
• HCl denatures• Pepsin hydrolyzes peptide bonds
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Digestion & Absorption– Small intestine
• Pancreatic enzymes– Trypsinogen trypsin– Chymotrypsinogen chymotrypsin– Procarboxypeptidases A & B carboxypeptidases– Proelastase– Collagenase
• Brush border peptidases– Aminopeptidases, dipeptdylaminopeptidases,
tripeptidases• Tripeptides hydrolyzed or absorbed at brush
border
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Digestion & Absorption• Intestinal brush border membrane
amino acid & peptide absorption– Amino acid transport
• Carriers required - passive & active transporters
– Peptide transport• PEPT1 • Co-movement of protons (H+)
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Digestion & Absorption• Intestinal basolateral membrane
transport of amino acids– Diffusion & sodium-independent
transport are main modes• Intestinal cell amino acid use
– Cells use or partially metabolize for release into blood
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Digestion & Absorption– Intestinal glutamine metabolism
• Primary energy source for enterocytes– Intestinal glutamate metabolism– Intestinal aspartame metabolism– Intestinal arginine metabolism– Intestinal methionine & cysteine
metabolism
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Digestion & Absorption• Amino acid absorption into
extraintestinal tissues– AAs enter portal vein to liver– Transport into hepatocytes– Transport into other cells -glutamyl cycle
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Amino Acid Metabolism• Metabolism of AAs includes:
– Protein synthesis– Amino acid catabolism– Hepatic catabolism
• Uses of aromatic amino acids• Uses of sulfur-containing amino acids• Uses of branched-chain amino acids• Uses of other amino acids
– Plasma amino acids & pools
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Synthesis of Plasma Proteins, Nitrogen-Containing Nonprotein Compounds, &
Purine & Pyrimidine Bases• Plasma proteins
– Albumin– Transthyretin (prealbumin)– Retinol-binding protein– Blood clotting proteins– Immunoproteins– Transport proteins– Acute phase proteins– Stress (heat) shock proteins (hsp)
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Synthesis of Plasma Proteins, Nitrogen-Containing Nonprotein Compounds, &
Purine & Pyrimidine Bases• Nitrogen-containing nonprotein
compounds– Glutathione - antioxidant, reacts with
H2O2, AA transport, conversion of prostaglandin H2 to D2 & E2
– Carnitine - FA transport– Creatine - part of phosphocreatine
(high-energy compound)
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Synthesis of Plasma Proteins, Nitrogen-Containing Nonprotein Compounds, &
Purine & Pyrimidine Bases– Carnosine - may be antioxidant– Choline - methyl donor, part of
acetylcholine & lecithin & sphingomyelin
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Synthesis of Plasma Proteins, Nitrogen-Containing Nonprotein Compounds, &
Purine & Pyrimidine Bases• Purine & pyrimidine bases
– Main constituents of DNA & RNA– Pyrimidines
• 6-membered rings containing N in positions 1 & 3
• Uracil, cytosine & thymidine– Purines
• 2 fused rings, N in positions 1, 3, 7, 9• Adenine & guanine
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Protein Synthesis Overview• Insulin & glucagon• Rate of protein digestion• Leucine• Fed vs. fasted state
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Amino Acid Catabolism Overview
• Transamination &/or deamination of amino acids– Deamination = removal of amino
group– Transamination = transfer of amino
group from one AA to AA carbon skeleton or -keto acid• Catalyzed by aminotransferases
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Amino Acid Catabolism Overview
• Disposal of ammonia--the urea cycle– NH3 combines with CO2 or HCO3
- to form carbamoyl phosphate
– Carbamoyl phosphate reacts with ornithine transcarbamoylase (OTC) to form citruline
– Aspartate reacts with citruline to form argininosuccinate
– Arginosuccinate is cleaved to form fumarate & arginine
– Urea is formed and ornithine is re-formed from cleavage of arginine
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Amino Acid Catabolism Overview
• An overview of metabolism of the carbon skeleton/-keto acid– Energy generation– Glucose & ketone body production– Cholesterol production– Fatty acid production
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Hepatic Catabolism & Uses of Aromatic Amino Acids
• Phenylalanine & tyrosine– Phenylalanine converted to tyrosine by
phenylalanine hydroxylase– Tyrosine
• Degradation begins with transamination to p-hydroxyphenylpyruvate
• Tyrosine used in other tissues for synthesis of L-dopa & catecholamines
• Melanin, thyroid hormones– Disorders of phenylalanine & tyrosine
metabolism
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Hepatic Catabolism & Uses of Aromatic Amino Acids
• Tryptophan– Catabolized to N-formylkynurenine– This is catabolized to formate & kynurenine– Used for:
• Protein synthesis • Energy, glucose, & ketone body production• Synthesis of serotonin & melatonin
– Disorders of tryptophan metabolism.
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Hepatic Catabolism & Uses of Sulfur (S)-Containing Amino Acids
• Methionine– Converted to S-adenosyl methionine
• SAM is principal methyl donor• Removal of methyl group yields S-adenosyl
homocysteine (SAH)– SAH converted to homocysteine– Homocysteine reacts with serine to form
cystathionine– Cystathionine cleaved to form cysteine & -
ketobutyrate– Propionyl CoA (made from -ketobutyrate) converted
to D-methylmalonyl CoA– Disorders of methionine metabolism
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Hepatic Catabolism & Uses of Sulfur (S)-Containing Amino Acids
• Cysteine– Used for protein & glutathione synthesis– Converted to cysteine sulfinate, used to produce
taurine– Taurine important in retina, functions as bile salt &
inhibitory neurotransmitter– Cysteine degradation yields pyruvate & sulfite
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Hepatic Catabolism & Uses of the Branched-Chain Amino Acids• Isoleucine, leucine, & valine• Taken up & transaminated
primarily in muscles
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Hepatic Catabolism & Uses of Other Amino Acids
• Lysine– Ketogenic - catabolism yields acetyl
CoA– Disorders of lysine metabolism
• Threonine– 3 pathways– Disorders of threonine metabolism
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Hepatic Catabolism & Uses of Other Amino Acids
• Glycine & serine– Produced from one another in reversible
reaction requiring folate– Disorders of glycine metabolism
• Arginine– Kidney - creatine synthesis– Liver - generation of urea & ornithine
• Histidine– Glutamate, carnosine, histamine
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Amino Acids Not Taken Up by the Liver: Plasma Amino Acids & Amino
Acid Pool(s)• Plasma concentrations rise after a
meal• Pool of about 150 g of endogenous
+ exogenous AAs • Re-use thought to be primary
source of AAs for protein synthesis• More nonessential than essential in
pool
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Interorgan “Flow” of Amino Acids & Organ-Specific Metabolism
• Glutamine & the liver, kidneys, & intestine– Ammonia transport– Hypercatabolic conditions
• Alanine & the liver & muscle– Inter-tissue transfer of amino groups– Liver: converted to glutamate or
glucose
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Interorgan “Flow” of Amino Acids & Organ-Specific Metabolism
• Skeletal muscle– Isoleucine, leucine, & valine– Nitrogen-containing compounds as
indicators of muscle mass & muscle/ protein catabolism
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Interorgan “Flow” of Amino Acids & Organ-Specific Metabolism
• Kidneys– Serine synthesis from glycine– Glycine catabolism to ammonia– Histidine generation from carnosine
degradation– Arginine synthesis from citruline– Tyrosine synthesis from phenylalanine– Guanidoacetate formation from arginine &
glycine for creatine synthesis
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Brain & Accessory Tissues• Biogenic amines &
neurotransmitters/hormones– Tryptophan - melatonin & serotonin– Tyrosine - dopamine, norepinephrine,
epinephrine– Glysine - inhibitory neurotransmitter– Taurine - inhibitory neurotransmitter– Aspartate - excitatory neurotransmitter– Glutamate - excitatory neurotransmitter or
converted to -amino butyric acid (GABA)
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Brain & Accessory Tissues• Neuropeptides
– Hormone-releasing factors– Endocrine effects– Modulatory actions on transmitter
functions, mood or behavior– Neurosecretory cells of hypothalamus
secrete– Synthesized from AAs via DNA codes
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Protein Turnover: Synthesis & Catabolism of Tissue Proteins
• Food intake & nutritional status• Hormonal mediation• AA pools connect 2 cycles of N
metabolism:– Protein turnover– Nitrogen balance
• Protein synthesis & degradation controlled separately
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Protein Turnover: Synthesis & Catabolism of Tissue Proteins
• Cellular protein degradation systems– Lysosomal degradation– Proteasomal degradation– Calcium or calcium-activated
proteolytic degradation
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Changes in Body Mass with Age
• Lean body mass increases throughout childhood– Changes in total fluid & ECF/ICF
• Gender differences develop during adolescence– Greater increase in males
• After 25, weight gain = fat gain• Lean mass decreases with increasing age
– More so in women than men– Body water declines too
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Protein Quality & Protein Intake
• Foods can be categorized as:– High-quality or complete proteins– Low-quality or incomplete proteins
• Evaluation of protein quality– Nitrogen balance/nitrogen status– Chemical or amino acid score– Protein digestibility corrected amino
acid score
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Protein Quality & Protein Intake
– Protein efficiency ratio– Biological value– Net protein utilization– Net dietary protein calories
percentage• Protein information on food labels
– % Daily Value
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Protein Quality & Protein Intake
• Recommended protein & amino acid intakes– RDA for adults = 0.8 g/kg– AI for birth-6 months– RDA for indispensible AAs – Negative effects of high protein
intakes controversial (no UL)– AMDR = 10%-35% kcal
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Protein Quality & Protein Intake
• Protein deficiency/malnutrition– Kwashiorkor
• Adequate energy with insufficient protein• Edema owing to loss of blood proteins
– Marasmus• Wasting, emaciation• Chronic insufficiency of energy & protein
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Perspective 6
Protein Turnover:Starvation Compared with
Stress
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Starvation vs. Stress• Starvation
– Protein synthesis decreases– Hormone balance adjusts– Adaptation - muscle catabolism slows
• Stress– Hypermetabolism– Lipolysis doesn’t lead to ketosis– Muscle catabolism undiminished– Protein turnover - immune response & acute
phase response