Blood: Cells and Plasma Proteins Beth A. Bouchard BIOC 212: Biochemistry of Human Disease Spring 2005

I. Major functions of blood and its components:  transport and distribution of essential nutrients to tissues  removal of waste products  defense against internal insult  repair of damaged tissues II. Two major components of blood: liquid phase and formed elements

Plasma “Buffy coat” Red blood cells Buffy coat Plasma - blood treated with anticoagulants to prevent clot formation then centrifuged to remove the cells Serum - blood that is allowed to form a fibrin clot then centrifuged to remove the cells and the clot

Red Blood Cells (Erythrocytes)  1011 produced per day  Anucleate  Lack intracellular organelles (incapable of protein synthesis and repair)  Contain specific proteins and ions  Transport oxygen, and remove CO2 and H+  Finite life span of 60-120 days before being destroyed in the spleen

Platelets  2-3 mm in diameter  150-400 x 106/mL blood Normal subcellular structures except they lack a nucleus Capable of mitochondrial protein synthesis  Platelet function is dependent upon their activation  Involved in blood clotting Contain secretory organelles called alpha-granules, which contain proteins important in blood clotting Circulate for 10 days before being destroyed

Plasma proteins Synthesized by liver or produced by plasma (B) cells Albumin Transferrin Ceruloplasmin Enzymes – coagulation enzymes, complement factors C-reactive protein – acute phase reactant Immunoglobulins – humoral immunity Transport proteins

ALBUMIN 66 kDa Accounts for ~50% of the total plasma protein and ~ 50% of the total liver protein production  Half-life ~ 20 days  Highly polar  At pH 7.4 it is anionic with 20 negative charges per molecule

Functions of Albumin  Transport of long chain fatty acids & sterols  Transport of bilirubin  Binding and solubilization of drugs

Regulation of colloidal pressure Decreases in albumin concentration cause edema Gaw: Clinical Biochemistry; Churchill Livingstone (1999), p. 44.

Causes of decreased plasma albumin: Decreased synthesis A. malnutrtion B. malabsorption C. advanced chronic liver disease II. Abnormal distribution or dilution A. overhydration B. increased capillary permeability like in septicemia Abnormal excretion or degradation A. nephrotic syndrome B. burns C. hemorrhage D. certain catabolic states E. protein losing enteropathies Rare congenital defects A. hypoalbuminemia B. analbuminemia

TRANSFERRIN Transports iron in plasma as ferric ions (Fe3+) – each transferrin molecule binds 2 Fe3+ Protects the body against the toxic effects of free iron Normally 30% saturated with Fe3+ - increased or decreased saturation is indicative of iron overload or deficiency, respectively  Decreased in inflammatory states due to excessive degradation of transferrin- Fe3+ complexes

CERULOPLASMIN Major copper transport protein  Regulates oxidation-reduction, transport and utilization of iron Increased concentrations are found in active liver disease or tissue damage Decreases are sometimes observed in individuals with Wilson’s disease

ENZYMES  Enzymes of the coagulation and complement cascade have a defined function in blood  Others reside elsewhere in the body and appear incidentally in the blood – their measurement is of diagnostic value Creatine kinase Alanine aminotransferase Acid phosphatase Amylase

C-REACTIVE PROTEIN (CRP)  Major component of the acute phase response and a marker of bacterial infection  Mediates the binding of foreign polysaccharides, phospholipids and complex polyanions, as well as the activation of complement  <1 mg/mL in normal plasma Slightly elevated levels of CRP are indicative of chronic, low-grade inflammation and have been correlated with an increased risk of cardiovascular disease

IMMUNOGLOBULINS Proteins produced and secreted by B cells specific for the foreign particle that stimulated their synthesis Five classes of Ig Multiple myeloma: arises from the aberrant proliferation of a single B cell. Light chains of Igs are produced in excess of heavy chains = paraproteins. Elevated serum protein levels are usually due to an increase in the Ig fraction and may indicate the presence of a paraprotein.