PLASMA PROTEIN

• Plasma


  One of the two major components of blood, the extracellular matrix

  
• Proteins


  The other major component of blood, the specialized cells (red blood cells, white blood cells, platelets)
• Objectives


  • Enumerate the major functions of blood
  • Define the 2 major components of blood
  • Differentiate plasma vs serum
  • Enumerate the general characteristics of plasma proteins
  • Describe the major classes of plasma proteins and their functions
  • Cite example of conditions affecting plasma proteins

  
• Major Functions of Blood

  • Respiration - supplies oxygen to cells and tissues
  • Nutrition - essential nutrients to cells, such as amino acids, fatty acids, and glucose
  • Excretion - removes carbon dioxide, urea and lactic acid (waste products)
  • Maintenance of acid-base balance in the body
  • Regulation of water balance
  • Regulation of body temperature
  • Defense against infection - WBC and Antibodies
  • Transport of hormones for regulation of metabolism
  • Transport of metabolites
  • Coagulation - platelets - blood to clot when bleeding
• Two Major Components of Blood

  Extracellular matrix (Plasma) and Specialized cells (Red blood cells, White blood cells, Platelets)

  
• Composition of Plasma: 92% water, 7% simple proteins, glycoproteins, lipoproteins

  
• Plasma


  Whole blood minus red blood cells

  
• Serum


  Plasma minus clotting factors (fibrinogen)

  
• Fibrinogen


  A protein involved in blood coagulation, an inactive protein that performs its function by converting into the active form fibrin
• Plasma Proteins


  • Albumin
  • Globulins (-Globulins, -Globulins, γ-Globulins - Immunoglobulins)
  • Fibrinogen
• Separation of Plasma Proteins

  1. Salting-out method (using ammonium or sodium sulfate)

  2. Electrophoresis (motion of charged particles relative to a fluid under the influence of an electric field)

  
• Salting-out method


  • Relies on the basis of protein solubility, most proteins are less soluble in solutions of high salt concentrations because the addition of salt ions shield proteins with multi-ion charges, allows for the separation of different proteins as they will precipitate at different points with increases in salt concentration
• Electrophoresis


  • Separates complex mixtures of proteins, investigates subunit compositions, verifies homogeneity of protein samples, purifies proteins for use in further applications, uses polyacrylamide gel as a size-selective sieve during separation
• Other Methods of Separation of Plasma Proteins

  • Cohn's fractional precipitation method
  • Immunoelectrophoresis technique
  • Ultracentrifugation

  
• Characteristics of Plasma Proteins

  • Most are synthesized and secreted by the liver, generally synthesized on membrane-bound polyribosomes, most are glycoproteins, many exhibit polymorphism, each has a characteristic half-life in the circulation, levels of certain increase during acute inflammatory states or tissue damage

  
• Functions of Plasma Proteins

  • Antiproteases
  • Blood clotting
  • Enzymes
  • Hormones
  • Immune defense
  • Involvement in inflammatory responses
  • Oncofetal
  • Transport or binding proteins
• Albumin


  The major protein in plasma, accounting for 60% of total plasma protein, not a glycoprotein, no polymorphism, 66 kDa, consists of one polypeptide chain of 585 amino acids, highly polar, anionic at pH 7.4
• Functions of Albumin


  • Transport of long chain fatty acids & sterols
  • Transport of bilirubin
  • Binding and solubilization of drugs
  • Regulation of colloidal pressure
• Causes of Decreased Plasma Albumin

  • Decreased synthesis (malnutrition, malabsorption, advanced chronic liver disease)
  • Abnormal distribution or dilution (overhydration, increased capillary permeability)
  • Abnormal excretion or degradation (nephrotic syndrome, burns, hemorrhage, certain catabolic states, protein losing enteropathies)

  
• Haptoglobin


  A glycoprotein that binds extracorpuscular (free) hemoglobin with high affinity, allowing degradation of the hemoglobin-haptoglobin complex
• Vasculature


  Prevents leaking into tissue
• Colloidal pressure


  Decreases in albumin concentration cause edema
• Causes of Decreased Plasma Albumin

  • Decreased synthesis
  • Abnormal distribution or dilution
  • Abnormal excretion or degradation

  
• Albumin


  Glycoprotein that binds extracorpuscular (free) hemoglobin with high affinity
• Haptoglobin (Hp)


  Binds with the free plasma hemoglobin to form a Haptoglobin-Hemoglobin complex, allowing degradative enzymes in the liver to gain access back to the hemoglobin and preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin
• Haptoglobin


  • Exists in 3 polymorphic forms: Hp 1-1, Hp 2-1, and Hp 2-2
  • Levels in human plasma vary and are of diagnostic use

  
• Transferrin


  1. globulin that transports iron in circulation to sites where it is needed
• Transferrin


  • Has 20 polymorphic forms
  • Normally 30% saturated with Fe3+
  • Abnormalities in glycosylation occur in congenital disorders of glycosylation and chronic alcohol abuse
• Ceruloplasmin


  1. globulin that is the major copper transport protein exporting it from the liver to the major tissues
• Ceruloplasmin


  • Binds 6 atoms of copper tightly
  • Regulates oxidation-reduction, transport and utilization of iron
• Lower-than-normal ceruloplasmin levels


  Indicate long-term (chronic) liver disease, problem absorbing nutrients from food (intestinal malabsorption), or Menkes syndrome
• Higher ceruloplasmin levels


  Indicate pregnancy, estrogen therapy, birth control pills, leukemia, Hodgkin lymphoma, primary biliary cirrhosis, and rheumatoid arthritis
• Copper


  Essential trace element that is a metal cofactor for a variety of enzymes and is involved in reactions involving dismutation, hydroxylation, and oxygenation
• Copper


  • Excess copper can oxidize proteins and lipids, bind to nucleic acids, and enhance the production of free radicals
  • Normal adult body contains about 100 mg of copper, mostly in bone, liver, kidney, and muscle
• Menkes Disease


  1. linked genetic disorder caused by a mutation in the ATP7A gene encoding a copper-binding P-type of ATPase, leading to copper deficiency and characteristic findings of kinky hair, growth failure, and nervous system deterioration
• Wilson's Disease


  Genetic disease due to mutation in the ATP7B gene encoding a copper-binding P-type of ATPase, leading to copper accumulation in liver, brain, kidney and red blood cells (copper toxicosis)
• 1. Antitrypsin


  Major serine protease inhibitor that inhibits trypsin, elastase and certain other proteases by forming complexes with them
• 1. Antitrypsin


  • Single-chain protein of 394 amino acids, contains 3 oligosaccharide chains
  • Synthesized by hepatocytes and macrophages
  • Has at least 75 polymorphic forms
• 1. Macroglobulin


  Large glycoprotein that binds and neutralizes many proteases and targets certain cytokines to tissues
• 1. Macroglobulin


  • Comprises 8-10% of the total plasma protein
  • Synthesized by a variety of cell types: hepatocytes, monocytes, astrocytes
  • Transports approximately 10% of the zinc in plasma