Protein

1
Chapter 6

• Protein

2
Functional Categories

• Catalysts - enzymes
• Hydrolases - cleave compounds
• Isomerases - transfer atoms in a molecule
• Ligases (synthases) - join compounds
• Oxidoreductases - transfer electrons
• Transferases - move functional groups

3
Functional Categories

• Messengers
• Hormones
• Structural elements
• Contractile proteins
• Fibrous proteins
• Globular proteins
• Immunoprotectors
• Immunoproteins (antibodies)

4
Functional Categories

• Transporters
• Albumin
• Transthyretin (prealbumin)
• Transferrin
• Ceruloplasmin
• Lipoproteins

5
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

7
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

10
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)

19
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 TurnoverStarvation Compared with Stress

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Starvation vs. Stress

• Starvation
• Protein synthesis decreases
• Hormone balance adjusts
• Adaptation - muscle catabolism slows
• Stress
• Hypermetabolism
• Lipolysis doesnt lead to ketosis
• Muscle catabolism undiminished
• Protein turnover - immune response acute phase
  response