PROTEINS (LEC-NOTES)

• Chief nitrogenous macromolecules of cellular structure and organization

  • Proteins
• Proteins


  • 50-70% of cell's dry weight
  • Most abundant macromolecules in the body
  • Only macromolecule expressed in g/dL
  • Unlike lipids and CHO, these are expressed in mg/dL
• Proteins

  Contains CHON

  
  

  Nitrogen: element that differentiates protein from other macromolecules
• Proteins


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

  Mostly synthesized in the liver except immunoglobulins which are produced by plasma cells
• Proteins


  They are water-soluble and amphoteric, can be (+/-) charged depending on pH
• Amino Acids


  Building blocks of proteins, have an amino group and carboxylic group
• Essential Amino Acids

  • Isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine
• Peptide bonds


  Holds amino acids together, also known as amide linkage
• Protein Structure

  • Primary
  • Secondary
  • Tertiary
  • Quaternary
• Primary Structure


  Refers to the identity & specific order of AA residues in the polypeptide chain (AA sequence), determines the overall shape of the protein
• Secondary Structure


  Conformation of the segments of polypeptide chain, maintained by hydrogen bonds
• Tertiary Structure

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


  Associated of several polypeptide subunits into a larger "oligomeric" aggregate unit
• Classification of Proteins

  • Simple proteins
  • Conjugated proteins
• Functions of Proteins

  • Acts as carrier for transport of different substances
  • Regulates the colloidal uncoating pressure
  • Plays a role in the coagulation cascade and complement fixation
  • Serves as a biocatalyst or enzyme
  • Maintenance of acid-base balance
  • Important in the repair of collagen
  • Can also generate energy
  • Produce motility through contractile elements
  • Assemble molecules
  • Serves as ion-channels or pumps
  • Serves as a receptor, hormones, cytokines
• Protein Metabolism

  1. Protein digestion begins in the stomach

  2. It will be completed in small intestine

  3. High acidity denatures the proteins making them susceptible to enzyme digestion

  4. Pepsin in the stomach responsible for digesting proteins into AA

  5. AA are then absorbed from the SI into the blood then transported into the liver
• GH, Insulin, Thyroid hormone

  Protein synthesis
• Glucocorticoids & Glucagon

  Protein catabolism
• Factors to differentiate proteins

  • Differential solubility
  • Molecular size
  • Molecular mass
  • Electrical charge
  • Surface adsorption
• Isoelectric point


  pH where proteins have NO NET CHARGE
• Zwitterion


  Ions that have 2 differing charges but the net charge on the molecule is zero
• Major Plasma Proteins

  • Prealbumin
  • Albumin
  • Globulin
  • Fibrinogen
  • Lipoprotein
  • Complement
  • C-reactive protein
• Plasma vs Serum

  • Plasma contains fibrinogen, serum does not
  • 4% decrease in TP content in serum due to the absence of fibrinogen
• Six Fractions of Major Plasma Proteins

  • Prealbumin
  • Albumin
  • Alpha-1-globulin
  • Alpha-2-globulin
  • Beta globulin
  • Gamma globulin
• Prealbumin (Transthyretin)


  Migrates anodal (faster) than albumin, second most predominant protein in CSF, functions as carrier protein for thyroid hormones and vitamin A
• Albumin


  Protein with highest concentration in the plasma, synthesized by liver, regulator of osmotic pressure, maintains oncotic pressure, negative acute phase reactant
• Hyperalbuminemia


  No clinical significance, caused by hemoconcentration or dehydration
• Hypoalbuminemia


  Caused by impaired synthesis (liver disease, diminished protein intake), malabsorption, malnutrition, nephrotic syndrome, increased catabolism (tissue damage, inflammation), severe burns
• Analbuminemia


  Absence of albumin
• Disalbuminemia


  Presence of two bonds in the albumin region
• Normal A/G ratio

  1.3 - 3:1
• Low A/G ratio

  Caused by liver diseases, infectious diseases, multiple myeloma, nephritis
• Alpha-1-Globulins

  • Alpha-1-antitrypsin
  • Alpha-1-fetoprotein
  • Alpha-1-acid glycoprotein (orosomucoid)
• Alpha-1-antitrypsin


  Accounts for the majority of alpha-1-globulin, complexes with trypsin in blood to inactivate it
• Alpha-1-fetoprotein


  Increased in amniotic and maternal serum in neural tube defects, liver tumor marker, decreased in maternal serum during pregnancy associated with Down's syndrome
• Alpha-1-acid glycoprotein (orosomucoid)


  Serves as carrier for steroid hormone
• Alpha-2-Globulins

  • Haptoglobin
  • Ceruloplasmin
  • Alpha-2-macroglobulin
• Haptoglobin


  Binds free hemoglobin, increased in acute phase and nephrotic syndrome, decreased in intravascular hemolysis and liver disease
• Ceruloplasmin


  Contains copper but does not transport it, increased in acute phase and pregnancy, decreased in Wilson's disease