Plasma Proteins and Lipoproteins

• plasma is a complex mixture of over 300 different proteins - 100 have been characterised and have known functions. 10 account for a total of 90-95% of total plasma proteins
• Total [plasma protein] range 63-83 g/l
• total plasma protein is not a common measurement, as a fall in one protein can be masked by the rise in another, so measure individual protein components instead.
• the concentration of plasma proteins is a balance between:

  • synthesis
  • rate of loss/catabolism
  • distribution between intra- and extra-vascular compartments
• some plasma proteins have specific roles - Ig, and albumin. whilst others are markers of disease
• an ideal biomarker is only produces in a diseased state
• plasma proteins vary considerably in their molecular weight, shape, density, half-life, chemical composition, charge and concentration from pg to g.
• Quantitatively albumin is the most abundant, the remainder of the plasma proteins are called globulins.
• most of the plasma proteins are synthesised in hepatocytes: some coagulation factors, albumin, most globulins, lipoproteins
• Complement proteins are also synthesised in macrophages, Igs in B lymphocytes
• Endocrine organs produce hormones
• The pancreas produces digestive enzymes
• most proteins are taken up by capillary endothelial cells or monocytes where they are catabolised.
• Small proteins are lost into the urine (through renal glomeruli) and intestinal wall and from the skin after severe burns
• roles of plasma proteins include:

  • Transport - smaller compounds
  • Nutrient reserve - mainly albumin in starvation/malnutrition
  • Maintenance of colloidal oncotic pressure
  • Defence reactions - Igs
  • Enzymes
  • Coagulation and fibrinolysis
  • Buffering of H - Acid/Base
• pre-albumin transports retinol, T3 and T3
• albumin transports inorganic constituents (calcium), free fatty acids, hormones (T4, T3, cortisol), excretory products (unconjugated bilirubin - insoluble haem product), drugs and other toxic substances
• hormone-binding proteins bind aldosterone, cortisol T4 and T3 and sex hormones (all lipid based)
• metal binding proteins transport ceruloplasmin (Cu) and transferrin (Fe) - small ions otherwise lost in filtrate in kidneys
• apolipoproteins transfer lipids
• plasma is water-based and so many poorly water-soluble constituents must be bound to plasma proteins to allow transport around the body
• The protein-bound fraction of many poorly water-soluble substances is physiologically inactive - only the unbound which exists in an equilibrium, is active.
• Oncotic pressure exerted across capillary walls will determine the distribution  of water between the plasma and the tissues I.e. between extra- and intra-cellular compartments
• NaCl (and other small molecules) are present at low concentrations but they can move across the capillary membranes thus do not contribute a great deal to osmotic pressure maintenance  in the vascular system
• Plasma proteins, especially the most abundant, albumin are too large to readily cross the capillary walls, thus have a high oncotic pressure - both [plasma protein] and hydrodynamic factors together determine the distribution of water and solutes across the capillary wall
• lack of volume in blood will cause shock in the body and cause an irregular heartbeat
• albumin has an osmotic pull for water which helps maintain water balance
• Immunoglobulins are synthesised by B lymphocytes in bone marrow as part of the immune response to invading pathogenic organisms
• Complement proteins are a group of 20 proteins which destroy invading bacteria and foreign cells - they target the antibody onto foreign cells top trigger the complex
• complement proteins act as enzymes to cause a cascade of cleavage reactions to activate the system.
• coagulation factors act as enzymes to cause a cascade of cleavage reaction to initiate coagulation and fibrinolysis
• protease inhibitors (alpha 2 macroglobulin) bind endopeptidases like trypsin and chymotrypsin resulting in a lack of enzyme activity - to stop the spread of inflamation
• renin is a proteolytic enzyme produced in the kidney, released into circulation in response to a decrease in circulating blood volume, renal perfusion pressure and loss of Na+.
• Renin converts angiotensinogen to angiotensin I (AI) which is then converted by ACE to angiotensin II(AII) and stimulates the release of aldosterone from the adrenal cortex, which promotes Na reabsorption in exchange for urinary H+ or K+
• renin is also important for water retention and balance
• LCAT is present predominantly on HDL particles - Lecithin cholesterol acyltransferase(LCAT) transfers the acyl group (fatty acid) from lecithin to cholesterol, forming cholesterol ester for return to the liver.
• lecithin cholesterol acyltransferase (LCAT) is present predominantly on HDL particles and transfers the acyl group (fatty acid) from lecithin to cholesterol, forming a cholesterol ester for return to the liver.
• lactate dehydrogenase (LDH), creatine kinase (CK), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) are all absent or present in very low levels normally, but in elevated levels when tissues, cells, and organs are damaged usually by disease processes.
• Chemical methods measure the ACTIVITY of proteins (enzymes) or the quantity of proteins is usually assessed by immunological methods ie. ELISA which used antigenic quantity, thus does not measure the function of a protein
• chemical and immunological methods are routinely used to measure the total albumin protein