PROTEINS and ENZYMES

Erythrocyte Sedimentation Rate (ESR): A high ESR occurs when the body is infected or under stress, and the
liver is releasing acute-phase proteins into the blood.
ACUTE-PHASE PROTEINS: Proteins released by the liver when the body is under stress.
• alpha1-Antitrypsin: Protease inhibitor. When there is tissue damage, the dead tissue releases proteases, so
the anti-proteases help to prevent further damage.
• alpha2-Macroglobulin: Indirect anti-protease that fixes proteases and allows macrophages to engulf them.
• C-Reactive Protein (CRP): Opsonin, help to fix antibodies to antigen to facilitate phagocytosis.
• Ceruloplasmin: Copper-carrying protein, and anti-oxidant.
• Complement Proteins: Inflammatory mediators.
• Ferritin: Iron protein-carrier.
• Fibrinogen: Clotting factor.
• Haptoglobin: Binds to hemoglobin in blood.
• Serum Amyloid A Protein: Apolipoprotein.
PROTEIN ELECTROPHORESIS: alpha1, alpha2, beta, and gamma zones all have distinct proteins.
• alpha1 Zone: Closest to the anode (right).
o Albumin: Albumin is the tall peak closest to the anode.
 Normal properties:
 50% of liver protein production; primary determinant of oncotic pressure.
 20-day lifespan in circulation. If albumin decreases, it won't show up until 20
days later.
 MW = 68 kDa, which is right at the margin for glomerular filtration. That's why
even mild glomerular disease leads to albuminuria.
 Albumin is decreased under a lot of circumstances:
 Renal disease, proteinuria.
 Times of stress or disease.
 Malnutrition, Kwarshiorkor.
 Albumin binds to bilirubin and Ca+2.
 A decreased albumin levels can significantly alter the laboratory values for
bilirubin and calcium. If albumin is low, then these lab-values will be falsely
low, and you must adjust them upward to get the real value.
o Pre-Albumin: Fetal albumin is called pre-albumin. It consists of two proteins.
 alpha-Fetoprotein (AFP):
 Anencephaly, Spina Bifida: AFP leaks out of the fetus and into the maternal
circulation, thus AFP is increased in maternal blood.
 Liver Cancer, Endodermal Sinus (Yolk-Sac) Tumor: The tumors contain
immature tissue thxat releases pre-albumin, thus AFP is increased.
 Transtherytin: Fetal form of TBG that carries T3 and T4 in fetal blood.
• alpha2 Zone:
o alpha2-Macroglobulin: Huge molecule that binds to proteases and thus allows macrophages to
engulf them, getting rid of the proteases.
o Haptoglobin: Binds to free hemoglobin in the plasma. Its maximum binding-capacity is about
10% of all hemoglobin in blood.

 If free haptoglobin is decreased (all bound up) and free hemoglobin is increased, then
that indicates intravascular hemolysis, such as that caused by blood-type incompatibility
or artifical heart valves.
o Ceruloplasmin
o GC Globulin
• beta Zone:
o LDL Lipoprotein
o Transferrin: Iron transporting protein.
o C3 Complement Factor
o beta2-Microglobulin: Part of the Major Histocompatibility Complex.
o Hemopexin: Binds free heme (hemoglobin degradation product) -- not hemoglobin itself, as in
Haptoglobin.
• gamma Zone: Closest to cathode (left).
o Immunoglobulins (Ig):
o C-Reactive Protein (CRP): Good marker during wound-healing. If it increases during woundhealing,
then the wound is probably getting infected.
 Originally discovered as a protein that binds to Streptococcus Pneumoniae.
o Fibrinogen:
o Lysozyme:
GAMMOPATHIES:
• Polyclonal Gammopathy: Broad gamma peak, indicating infection.
• Monoclonal Gammopathy: Narrow gamma peak. Differential:
o Multiple Myeloma, 60%. Malignancy of IgG-secreting plasma cells.
o Waldenstrom Macroglobulinemia, 10%. Hypersecretion of IgM.
o Lymphomas, Leukemias, 10%
o Monoclonal Gammopathy of Unknown Significance (MGUS), 10%
o Rare causes: Heavy chain disease, primary amyloidosis, solitary plasmacytoma.
• Hypogammaglobulinemia: No peak or shallow peak in gamma range.
o Due to inherited immune deficiency:
 X-Linked IgA Deficiency: Common, 1/750 births.
 Agammaglobulinemia: Rare.
o Acquired causes: Malignancies, immunosuppressive drugs, HIV, measles, malnutrition.
PLASMA ENZYMES:
• Alkaline Phosphatase (Alk.Phos.): Increased Alk.Phos. indicates:
o Cholestasis
o Increased bone growth or reformatuion. Osteoblasts secrete Alk.Phos.
• Alanine Aminotransferase (ALT): Increased ALT indicates liver damage. It is released into circulation
from damaged or necrotic liver cells.
• Aspartate Aminotransferase (AST): AST is released from a variety of damaged cells. Increased ALT
indicates:
o Liver damage
o Post-MI
o General cellular injury.
• Myocardial Infarct (MI): CAL is a mnemonic to remember the order in which enzymes increase:
o Creatinine Kinase (CK): 4-8 hrs. post-MI
o Aspartate Aminotransferase (AST): Goes up next.
o Lactate Dehydrogenase (LDH): Last one to go up.
• Creatinine Kinase (CK): Isozymes
o CK-MM: 99% of skeletal muscle, and about 77% of myocardium.
o CK-MB: About 22% of myocardium, but it is not found in any other tissues, so CK-MB is a
significant marker for myocardial infarct.
o CK-BB: Forms greater than 90% of CK in other tissues, such as CNS, colon, and ileum.
• Lactate Dehydrogenase (LDH): Isozymes
o LDH-1: The predominant isozyme in myocardial tissue. High LDH-1 indicates MI.
• LDH-Flip: LDH-5 is normally highest, but in cases of MI LDH-1 may be higher. This is called an LDHflip
and is suggestive of MI.
o LDH-2 thru LDH-4: Minor isozymes.
o LDH-5: The predominant isozyme in liver and skeletal muscle. It is normally the highest, except
in cases of MI LDH-1 may be higher.
PROTEINURIA: Can be caused by three mechanisms:
• OVERFLOW:
o Normal proteins in blood: hemoglobinuria, myoglobinuria.
o Abnormal proteins in blood: Bence-Jones protein (IgG light-chains found in Mutiple Myeloma).
• GLOMERULAR: Primarily albuminuria.
o Fever, glomerulonephritis cause higher renal permeability.
o Altered hemodynamics (such as exercise) can transiently cause proteinuria.
• TUBULAR:
o Tubular damage due to heavy-metal poisoning, drug toxicities.
o Interstitial nephritis, pyelonephritis.
o beta2 and alpha1 Microglobulin will be found in urine. They are normally filtered and
reabsorbed, but with tubular disease they won't be reabsorbed.