Proteins in Human Serum and Plasma

Proteins in Human Serum and Plasma

• Plasma contains over 300 proteins.
• Many proteins have specific biochemical roles.
• Diseases may occur if protein concentrations are reduced in plasma.
• Disease processes like trauma, infection, and inflammation can change plasma protein concentrations.
• Measuring specific proteins can help monitor disease progression and treatment response.

Protein Synthesis

• Hepatocytes produce many plasma proteins.
• Macrophages also produce complement system proteins.
• B lymphocytes produce immunoglobulins.

Metabolism of proteins

• The amount of protein in the vascular system depends on synthesis and breakdown rates.
• Distribution between intravascular and extravascular spaces is also important.
• The concentration depends on the relative amounts of protein and water.

Protein Catabolism and Loss

• Plasma proteins are taken up by pinocytosis in capillary endothelial cells or phagocytes.
• Small proteins and peptides not bound to carriers are lost passively through the renal glomeruli and intestinal walls.
• Some reabsorbed by renal tubular cells or after intestinal lumen digestion.
• Others are broken down by renal tubular cells.

Other Proteins and Bioactive Peptides

• Insulin, parathyroid hormone, and growth hormones have very short half-lives.
• These proteins are degraded by exopeptidases or endopeptidases.
• Receptor-mediated uptake is also involved.

Functions of Plasma Proteins: Control of Extracellular Fluid Distribution

• Distribution of water between intravascular and extravascular compartments is affected by colloid osmotic pressure.
• Primarily influenced by albumin.

Functions of Plasma Proteins: Transport

• Albumin and specific binding proteins carry hormones, vitamins, lipids, bilirubin, calcium, trace metals, and drugs.
• Combining with proteins allows poorly water-soluble substances to be transported in plasma.
• Protein-bound forms of substances are often physiologically inactive.

Functions of Plasma Proteins: Inflammatory Response and Control of Infection

• Immunoglobulins and complement proteins are part of the immune system.
• Acute phase reactants like CRP are involved in the inflammatory response.

Abundant Components of the Circulating Proteome

• The document lists several proteins as abundant components.

Prealbumin (Transthyretin)

• Composed of four identical subunits.
• Binds and transports triiodothyronine (T3) and thyroxine (T4).
• Molecular weight is 35 kDa.
• Its concentration is used to assess protein nutrition adequacy due to its short half-life (approximately 2 days).

Albumin

• Most abundant plasma protein, accounting for almost half of plasma protein mass.
• Synthesized by the liver.
• Molecular weight of 66,438 Da.
• Found in various body fluids, including interstitial fluid, cerebrospinal fluid (CSF), urine, and amniotic fluid.
• More than half of the total albumin pool is in the extravascular space.
• Chemically and biologically stable, resisting denaturation at high temperatures.
• Circulates with a half-life of 15-19 days.
• Major component of colloid osmotic pressure.
• Transports various substances including fatty acids, lipids, bilirubin, drugs, amino acids, tryptophan, calcium, and metals.
• Increased levels are seen in dehydration and excessive venous stasis.
• Low levels (hypoalbuminemia) are associated with conditions like cirrhosis, nephrotic syndrome, heart failure, and malnutrition.
• Urinary protein/albumin measurement helps assess renal protein loss.

α1-Antitrypsin (AAT)

• Inhibits proteases in the blood.
• Specifically targets neutrophil elastase.
• Helps limit proteolytic activity in inflammation.
• Released and synthesized by hepatocytes.
• Molecular weight of 51 kDa.

Ceruloplasmin (Cp)

• An α2-globulin, containing around 95% of serum copper.
• Each molecule binds 6-8 copper atoms.
• Molecular weight is approximately 132 kDa.
• Primarily synthesized by hepatic parenchymal cells, with some from macrophages and lymphocytes.
• Half-life is 4-5 days.

Haptoglobin (Hp)

• An α2-glycoprotein that binds hemoglobin.
• Synthesized by hepatocytes.
• Aids in hemoglobin clearance (scavenges hemoglobin in the vascular space).
• Prevents renal clearance of hemoglobin.
• Free hemoglobin, released from destroyed red blood cells, forms a strong non-covalent complex with Hp.
• The complex binds to CD163 receptors on hepatocytes and macrophages.
• Quickly cleared by the reticuloendothelial system.
• Heme and iron are recycled.
• Sufficient Hp circulates to bind and clear 3 grams of Hb, which prevents free Hb in the body.
• Internalized, processed, degraded, releasing heme for processing to release iron.
• Recycled into constructing new Hb proteins.
• If not bound to Hb, Hp is cleared in the plasma in 3 - 5 days.

Transferrin

• Principal plasma transport protein for iron (Fe³⁺).
• Single polypeptide chain, with N-linked oligosaccharides and homologous domains, each with an Fe³⁺-binding site.
• Synthesized mainly in the liver.
• Reversibly binds two ferric (Fe³⁺) ions at physiological pH, but with lower affinity at decreased pH.
• Enables release of iron in intracellular compartments.
• Receptor-mediated endocytosis after cellular delivery allows recycling of apotransferrin.

β2-Microglobulin

• Small protein (11.8 kDa).
• Noncovalently bound light chain of class I MHC molecules.
• Found on the surface of all nucleated cells.
• Shed into the blood, particularly by B lymphocytes and some tumor cells.
• Small size enables efficient glomerular filtration.
• Plasma half-life is approximately 100 minutes.

This quiz explores the diverse roles and functions of proteins found in human serum and plasma. It covers protein synthesis, metabolism, and the implications of protein concentration changes due to various diseases. Test your knowledge on the production, function, and importance of plasma proteins in the human body.