Inflammation and Smoking Effects

Biochemistry Study Notes

• Prealbumin (Transthyretin):
  • Not an immature form of albumin, but a different protein.
  • Also known as transthyretin.
  • Transports thyroid hormones (T3 and T4).
  • Migrates faster than albumin during electrophoresis.
  • Small glycoprotein.
  • Molecular weight of 62 kDa.
  • Rich in tryptophan, with 0.5% carbohydrates.
  • Low blood level (0.25g/L).
  • Short half-life (2 days).
  • Useful for diagnosing diseases related to protein nutrition or liver function, but less reliable due to low blood concentration.

Globulins

• Alpha-1 Globulins:

  • Alpha1-antitrypsin (A1AT):
    • Neutralizes trypsin and trypsin-like enzymes, which break down proteins.
    • Also called Alpha1-Antiproteinase, inhibiting a wide range of proteases.
    • Molecular weight of 53 kDa.
    • Makes up 90% of alpha-1 globulin fraction in serum.
    • Polymorphic with over 75 forms, MM is the most common.
    • Genetic deficiency (ZZ genotype): severe deficiency, 10% reduction in A1AT activity, high risk of emphysema.
    • SZ genotype also associated with deficiency, with reduced or defective A1AT activity when no M copy is present.
    • Role in elastase regulation: inhibits elastase, an enzyme produced by macrophages during inflammation. Inhibits elastase from breaking down tissue.
    • Oxidation of Alpha1-Antitrypsin: Smoking can oxidize methionine-358, preventing binding and hindering elastase inhibition.
  • Other alpha-1 globulins:
    • alpha1-antitrypsin, ceruloplasmin, alpha-1-fetoprotein, haptoglobin, a1-acid glycoprotein, retinol binding protein.

• Alpha-2 Globulins:

  • Haptoglobin (HP):
    • Acute phase protein.
    • Molecular weight of 90 kDa, a tetramer with 3 phenotypes (Hp1-1, Hp2-1, Hp2-2).
    • Binds to free hemoglobin to prevent loss in urine, helping iron recycling.
    • Half-life is 5 days, becomes shorter(90 minutes) when bound to hemoglobin.
    • Crucial in iron metabolism and preventing iron loss in the urine.

• Beta Globulins:

  • Ceruloplasmin:
    • 160 kDa copper-containing glycoprotein.
    • Regulates copper levels in the circulation.
    • 90% of blood copper is bound to ceruloplasmin, with albumin transporting the remainder.
    • Crucial in tissue copper regulation.
    • Low levels can lead to Wilson's disease.

• Gamma Globulins:

  • C-reactive protein (CRP):
    • Acute phase protein, works against C fraction of microorganisms, and helps in defense against bacteria and foreign substances.
    • High levels can indicate inflammation or diseases such as acute rheumatic fever, bacterial infection, or gout.
    • Good monitoring marker with levels peaking after 48 hours.

Diseases and Liver Function

• Diseases: Renal failure impacts protein levels in circulation. Most plasma proteins are made in the liver, except for gamma globulins. Low liver function reduces protein synthesis. Elevated gamma globulin suggests cancer (myeloma).