CC FINALS

• Chief nitrogenous macromolecules of cellular structure & organization

  • 50-70% of cells dry weight
• Proteins


  Consist of a definite number of amino acids arranged in a specific sequence
• Proteins


  • Covalently linked polymers of amino acids
  • Most abundant macromolecules in the body and only macromolecules expressed in g/dl
  • Contains carbon, hydrogen, oxygen and nitrogen (CHON)
  • Nitrogen is an element that differentiates proteins from other macromolecules
• Peptide bond


  Formed upon removal of a water molecule, holds the amino acid together (AMIDE LINKAGES)
• Amphoteric


  Either positively charged at acidic pH or negatively charged at alkaline pH
• Proteins


  Synthesized in the liver & secreted by the hepatocyte into the circulation EXCEPT immunoglobulins (plasma cells)
• Proteins provide 12 – 20% of the total daily body energy requirement
• Proteins compose 50 – 70% of the cell's dry weight
• Primary structure


  Identity & specific order of amino acid residues in the polypeptide chain (amino acid sequence), determines the overall shape of the protein
• Secondary structure


  Conformation of the segments of a polypeptide chain, maintained by hydrogen bond
• Secondary structures


  • Alpha-helix
  • Beta-pleated sheets
  • Random coils
• Tertiary structure


  Intramolecular folding of the polypeptide chain into a compact 3-dimensional structure, maintained by covalent disulfide bonds
• Quaternary structure


  Association of several polypeptide chains into larger "oligomeric" aggregate unit
• Factors affecting proteins


  • Differential solubility
  • Molecular size
  • Molecular mass
  • Electrical charge
  • Surface absorption
• Differential solubility


  Proteins are affected by pH, temperature, ionic strength, and dielectric constants, Isoelectric point is the pH where the proteins have no net charge, Zwitterion is an ion that has 2 different charges but their net charge is 0
• Molecular size


  Can be accomplished through ultracentrifugation or dialysis
• Molecular mass


  Can be accomplished through mass spectrometry
• Electrical charge


  Can be accomplished using ion exchange chromatography and electrophoresis
• Surface absorption


  Can be done using chromatography
• Classification of proteins


  • Simple proteins
  • Conjugated proteins
• Simple proteins


  Contain peptide chains which on hydrolysis yield only amino acids, can be globular or fibrous
• Conjugated proteins


  Composed of a protein (apoprotein) & nonprotein moiety (prosthetic group) like lipid (lipoprotein), carbohydrate (glycoprotein), metals (metalloprotein)
• Functions of proteins


  • Repair body tissues
  • Important in blood coagulation and immunologic function
  • Transport of metabolic substances
  • Maintenance of osmotic pressure
  • Maintenance of blood pH (buffers)
  • Biocatalysts
  • Complement fixation, coagulation cascade
  • Maintains acid base balance
  • Forms many important intra and extracellular structures
  • Generates energy through catalysis and electron transfer
• Protein metabolism


  • Dietary Intake
  • Absorption
  • Production
  • Storage
  • Destruction
• GH, Insulin, & Thyroid hormone increase protein synthesis, Glucocorticoids & glucagon increase protein catabolism
• Protein digestion begins in the stomach and will be completed in the small intestine, High acidity denatures protein making them susceptible to enzyme digestion (PEPSIN)
• Major plasma proteins


  • Pre-albumin (Transthyretin)
  • Albumin
  • Globulins
  • Fibrinogen
  • Lipoproteins
  • Complement
  • C-reactive protein

  
• Pre-albumin (Transthyretin)


  2nd most predominant protein in CSF, Migrates ahead of albumin toward the anode, Rich in tryptophan and contain 0.5% carbohydrate, Serves as a transport protein for T3, T4 and retinol (Vit. A)

  
• Albumin


  Largest plasma protein fraction (52-62%), Synthesized in the liver at a rate that is dependent on protein intake, Serves as circulating reservoir of amino acids, Regulator of osmotic pressure, Transport protein, A "negative acute phase reactant"

  
• Normal life span of albumin is 15-19 days in circulation

  
• Albumin serves as TRANSFER PROTEIN carrier for most substances
• Albumin levels


  • Increased: dehydration, prolonged tourniquet application, specimen evaporation
  • Decreased: inflammation, hepatic disease, urinary loss, gastrointestinal loss, protein calorie malnutrition, burn injury, edema and ascites

  
• Analbuminemia is the absence of albumin, Bisalbuminemia is the presence of two albumin bands instead of the single band usually seen by electrophoresis
• Reference value for albumin is 3.5 – 5.0 g/dL (35 – 50 g/L)

  
• Causes of increased albumin


  • Hemoconcentration, dehydration, excessive albumin infusion
• Causes of decreased albumin


  • Impaired synthesis (1O= liver disease; 2O = diminished protein intake), Malabsorption or malnutrition, Nephrotic syndrome (renal loss), Severe burns, Increased catabolism due to tissue damage & inflammation
• Globulins


  Heterogenous complex mixture of protein molecules (α1, α2, β and γ fractions), Elevated concentration in early cirrhosis will balance loss of albumin resulting to normal levels of total protein, Normal A/G ratio : 1.3 – 3 : 1, Low A/G ratio: liver diseases, infectious diseases, multiple myeloma, nephritis

  
• Alpha 1 globulins


  • α-1-antitrypsin
  • α-1-fetoprotein
  • α-1-Acid Glycoprotein (orosomucoid)
  • α-1-Antichymotrypsin
• α-1-antitrypsin


  90% of the α1-globulin band, Complexes w/ trypsin in blood to inactivate it, An acute phase reactant, Neutralize trypsin-like enzymes, Major inhibitor of protease activity
• α-1-fetoprotein


  Synthesized initially by the fetal yolk sac & then the parenchymal cells of the liver, Used as a liver tumor marker (hepatic & gonadal CA), Screening test for any fetal conditions, Increased in amniotic fluid & maternal serum in neural tube defects, Decreased in maternal serum during pregnancy associated w/ Down's syndrome