Lecture 2/19

• albumins include prealbumin and albumin
• prealbumin

  • manufactured in the liver
  • has half-life of 2 days
  • MW: 55 kDA
  • migrates farther than albumin
  • quantity is small and rarely seen on electrophoresis
• albumin - makes up largest part of serum proteins; around 60%
• • Albumin

  1. Synthesized in liver
  2. Migrates fastest in normally detected proteins
  3. MW of 66 kDa
• albumin - decrease in renal disease and intestinal mucosal diseases pathophysiology

  • Renal disease - kidneys compromised; albumin slips through into urine
  • Intestinal mucosal diseases - not absorbing protein
• albumin - increased during dehydration

  1. Only a relative increase
  2. When patient rehydrated, disappears
  3. This happens with almost all solutes (as plasma is decreased)
• • Bisalbuminemia - two distinct types of albumin
  • Double band of albumin will occur on electrophoresis
• a-1 globulins

  • A-1 antitrypsin - acute phase reactant; constitutes 90% of alpha-1 globulins; abnormal levels are picked up on electrophoresis; 
  • Function - neutralizes trypsin enzymes
  • Deficiency of this protein is associated with severe emphysema and juvenile hepatic cirrhosis
• • Trypsin is a proteinase, dissolves proteins if not neutralized 
  • Can eat away at elastic proteins that allow alveoli to shrink upon exhalation; leads to emphysema
• prealbumin

  • known as transthyretin
  • main function: transports thyroid hormones and retinol (vitamin A)
• a-1 globulins

  • A-1 fetoprotein (AFP)
  • Protein not normally present in adults 
  • Synthesized by embryo in the yolk sac 
  • Later, synthesized by parenchymal cells of liver 
• • Parenchymal cells - functional cell that manufactures things; not hepatocyte yet
• A-1 fetoprotein (AFP)

  • Can be detected in amniotic fluid and maternal plasma
  • Normal maternal screening period - between 15 - 20 weeks
  • Two AFP tests
  • Maternal AFP - testing for fetal protein in mother
  • AFP tumor marker - some cancers cause increase in AFP
  • Found in adults with hepatic cancer, some gonadal tumors; if present, AFP will show as separate band from a-1 and a-2 globulins
• A-1 fetoprotein (AFP)

  • Increased levels are associated with spina bifida, neural tube defects, GI malformation, general fetal distress, twins
  • Decreased levels are associated with Down’s Syndrome and trisomy 18
• a-1 globulins

  • A-1 acid glycoprotein - used as a carrier for alkaline based drugs
  • Inactivates some basic proteins
  • Helps in synthesis of membranes and collagen
  • No significance if decreased 
• a-1 globulins

  • A-1 lipoprotein - also known as HDL
  • Manufactured by liver
  • helps carry lipids
• a-1 globulins

  • A-1 antichymotrypsin
  • May signal protein synthesis in trauma or injury
  • Increase in inflammation and in inflammatory diseases
  • Can be decreased in liver disease and asthma
• a-1 globulins

  • Inter-a-trypsin inhibitor 
  • Increased in inflammation
  • Will migrate between a-1 and a-2 bands on high resolution electrophoresis
• a-1 globulins

  • GC-globulin - aka vitamin D binding protein
  • Also migrates between a-1 and a-2 on high resolution electrophoresis
  • Increased in third trimester of pregnancy and estrogen oral contraceptives
  • Decreased in severe liver disease and protein losing syndromes
• • Electrophoresis is generally run at normal voltage for short period of time, while in high res electrophoresis, run at higher voltage and have cooling function, as higher voltage means more heat and will denature proteins if it gets too hot
  • Spreads proteins into many more fractions
• a-2 globulins include haptoglobins, ceruloplasmin, and a-2 macroglobulin
• a-2 globulins

  • Haptoglobins 
  • Synthesized by hepatocytes
  • Binds hemoglobin by its alpha chain
  • Any abnormal protein without an alpha chain will not be bound by haptoglobin 
  • Complex of haptoglobin and hemoglobin is removed by mononuclear phagocytic system (previously known as reticuloendothelial system) within minutes of formation
• RES - system by which old RBCS removed
• a-2 globulins

  • haptoglobins
  • Increased in inflammation, rheumatoid arthritis, burns, and nephrotic syndrome
  • Decreased in intravascular hemolysis and red cell trauma
  • Haptoglobin picks up free hemoglobin so this makes sense
  • Haptoglobin is a limited resource; so if used up, will decrease
• • Nephrotic syndrome - glomerulus more porous; more fluids and low molecular weight proteins are loss; comparatively, slight increase in bigger proteins such as haptoglobin
• a-2 globulins

  • Ceruloplasmin - copper containing glycoprotein that acts like an enzyme
  • Synthesized in the liver
  • Contains either 6 or 8 copper ions
  • Half of them have 1+ oxidation state, while other half has 2+ oxidation state
  • Carries 90% of the copper in the body 
• a-2 globulins

  • ceruloplasmin
  • Increased in inflammation, pregnancy, certain cases of cancer, oral estrogen therapy, contraceptive use
  • Decreased in Wilson’s disease
  • Also decreased in malnutrition, malabsorption, severe liver disease, and nephrotic syndrome
• Wilson's Disease

  • Autosomal recessive trait with inability to make functional ceruloplasmin
  • Excess copper builds up in skin, liver, and CNS, especially the brain; results in neurologic damage
  • Copper in eyes - irreversible CNS damage
• a-2 globulins

  • A-2 macroglobulin - similar to a-1 antitrypsin 
  • Synthesized in liver
  • Inhibits proteases
  • Controls site and/or extent of inflammation
  • Increased in pregnancy, diabetes mellitus, and nephrotic syndrome
  • Decreased in rheumatoid arthritis and multiple myeloma
• B globulins include pre-B-lipoprotein, transferrin, hemopexin, B-lipoprotein, B2-microglobulin, complement, fibrinogen, and C-reactive protein
• B globulins

  • pre-B-lipoprotein
  • Aka VLDL (very low density lipoprotein)
  • Involved in transport of lipids (will go in more details in lipids)
• B globulins

  • B-lipoprotein
  • Aka LDL (low density lipoprotein)
  • Involved in transport of lipid
• B globulins

  • Transferrin
  • Major beta protein 
  • Synthesized in liver
  • Transports iron
  • Prevents excretion and deposition of iron into tissues 
  • Important as iron will do oxidative damage to cells if not bound to something
• B globulins - transferrin

  • Can carry two iron molecules in ferrous (Fe2+) state
  • Increased in pregnancy, iron deficiency anemia
  • Decreased in liver disease, malnutrition, nephrotic syndrome, and inflammation
• • In IDA - liver makes more transferrin in effort to grab onto whatever iron it can 
• B globulins

  • Hemopexin
  • Scavenger that picks up heme and porphyrins in circulation
  • Manufactured in liver
  • Complex is destroyed in liver
  • Decreased in hemolytic disorders
  • Increased in pregnancy, muscular dystrophy, and some cancers
• • Haptoglobin vs hemopexin
  • Hemopexin binds to heme or porphyrin
  • Haptoglobin binds to globin or protein part
• B globulins

  • B2- microglobulin
  • Aka beta chain 
  • Component of HLA antigens
  • HLA - human leukocyte antigen aka MHC (major histocompatibility complex)
  • Usually filtered out by glomerulus but reabsorbed in proximal tubule 
• B globulins

  • B2 microglobulin
  • Increased in impairment of kidney clearance, inflammatory diseases, some neoplasms
  • Increase in HIV patients without kidney disease is indicative of lymphocyte destruction
  • Can quantify beta-2 microglobulin by immunoassay 
• B globulins

  • Complement 
  • Group of proteins that act in sequence to destroy cells
  • Increased in an inflammatory response
  • Decreased in malnutrition, lupus, and DIC