Proteins In Human Serum and Plasma PDF

Proteins in Human Serum and Plasma Lec6 Dr. Ula Abbas Zeki ⊳ Plasma contains over 300 proteins. ⊳ Many of these have a specific biochemical role, and organic disease may result when their concentration in plasma is reduced. ⊳ Conversely, disease processes such as trauma, infection a...

Proteins in Human Serum and Plasma Lec6 Dr. Ula Abbas Zeki ⊳ Plasma contains over 300 proteins. ⊳ Many of these have a specific biochemical role, and organic disease may result when their concentration in plasma is reduced. ⊳ Conversely, disease processes such as trauma, infection and inflammation may lead to changes in the concentration of a wide range of plasma proteins. ⊳ The measurement of some specific proteins may have a valuable clinical role in monitoring progression of a disease or response to therapy. 2 Protein synthesis Hepatocytes synthesize many plasma proteins; and proteins of the complement system are also made by macrophages. Immunoglobulins are mainly derived from the B lymphocytes of the immune system. 3 Metabolism of proteins The amount of protein in the vascular compartment depends on the balance between the rates of synthesis and the rate of catabolism or loss. also the relative distribution between the intravascular and extravascular compartments is important , as the concentration depends on the relative amounts of protein and water in the vascular compartment. 4 Protein catabolism and loss Most plasma proteins are taken up by pinocytosis into capillary endothelial cells or mononuclear phagocytes, where they are catabolized. Proteins and peptides substantially smaller than albumin and not bound to carriers are lost passively through the renal glomeruli and intestinal wall. Some are reabsorbed, either directly by renal tubular cells or after digestion in the intestinal lumen; others are catabolized by renal tubular cells 5  Other proteins and bioactive peptides such as insulin, intact parathyroid hormone, and growth hormone have much shorter circulating half-lives of only a few minutes, indicating receptor- mediated uptake or degradation by exopeptidases or endopeptidases. 6 Functions of plasma proteins 1. Control of extracellular fluid distribution The distribution of water between the intravascular and extravascular compartments is influenced by the colloid osmotic effect of plasma proteins, predominantly albumin. 7 2. Transport Albumin and specific binding proteins transport hormones, vitamins, lipids, bilirubin, calcium, trace metals and drugs. Combination with protein allows poorly water-soluble substances to be transported in plasma. The protein-bound fraction of many of these substances is physiologically inactive, unlike the free unbound fraction. 8 3. Inflammatory response and control of infection The immunoglobulins and the complement proteins form part of the immune system and the latter, together with a group of proteins known as acute phase reactants, like CRP, are involved in the inflammatory response. 9  “ Abundant Components of the Circulating Proteome 10 Prealbumin (Transthyretin) ⊳ is composed of four identical noncovalently bound subunits with the capacity to bind and transport 10% of circulating triiodothyronine (T3) and thyroxine (T4). ⊳ molecular weight 35 kDa ⊳ Its concentrations are often used as an indicator of adequacy of protein nutrition because of its relatively short half-life (~2 days) 12 Albumin  albumin is the most abundant plasma protein, accounting for about half of the plasma protein mass. synthesized by the liver, molecular weight of 66,438 Da. It is a major component of most body fluids, including interstitial fluid, CSF, urine, and amniotic fluid. More than half of the total pool of albumin is in the extravascular space. It is both chemically and biologically stable because it resists denaturation at higher temperatures than most plasma proteins and circulates with a half-life of 15 to 19 days.  Albumin has two critical biologic functions. 1. It serves as the major component of colloid osmotic pressure. 2. It serves as a transporter for a diverse range of substances, including fatty acids and other lipids, bilirubin, foreign substances such as drugs, thiol containing amino acids, tryptophan, calcium, and metals.  Increased albumin concentration is found in dehydration excessive venous stasis is applied during venipuncture. Hypoalbuminemia Low albumin may arise as a consequence of a number of conditions, including cirrhosis, nephrotic syndrome, heart failure and malnutrition. Measurement of urinary protein or albumin concentration is important to exclude a renal cause of protein loss. α1-Antitrypsin AAT ⊳ Proteases such as trypsin, chymotrypsin, elastase and thrombin are continually being released into the blood in small amounts from a number of sources, including the pancreas, leucocytes and intestinal bacteria. ⊳ AAT is one of several plasma proteins that inhibit the activity of these proteases, particularly neutrophil elastase, and may function to limit proteolytic activity at sites of inflammation. (α1‐anti‐protease) ⊳ release and synthesized from the hepatocytes, mol. weight 51 kDa. Ceruloplasmin (Cp)  is an α2-globulin that contains about 95% of serum copper. Each molecule of Cp contains 6 to 8 tightly bound copper atoms. molecular weight of approximately 132 kDa. Cp is synthesized primarily by hepatic parenchymal cells, with small amounts from macrophages and lymphocytes. half-life is 4–5 days Haptoglobin  Haptoglobin (Hp) is an α2-glycoprotein that binds hemoglobin ,synthesized by hepatocytes The hallmark function of Hp is to facilitate Hb clearance. (scavenges hemoglobin in the vascular space). This process prevents renal clearance of hemoglobin ⊳ Free Hb released into the blood is a natural phenomenon during the destruction of senescent RBCs or if bleeding occur. ⊳ Hp forms a strong noncovalent complex with Hb (Hp-Hb complex) ⊳ Hp-hemoglobin complexes are bound by CD163 receptors on hepatocytes, Kupffer cells, and tissue macrophages , and rapidly cleared by the reticuloendothelial system, which degrades protein and recycles heme and iron. 23 24 ⊳ There is sufficient Hp in circulation to bind and clear 3g of Hb, which would prevent free Hb circulation in the body ⊳ Hb that is bound with Hp for clearance is internalized, processed, and degraded to release heme for further processing to release iron where it can be recycled to construct new Hb proteins. ⊳ When not bound to Hb, Hp is cleared from the plasma in 3–5 days. 25 Transferrin ⊳ Transferrin is the principal plasma transport protein for iron (Fe⁺ᵌ) ⊳ It is a single polypeptide chain, with two N-linked oligosaccharides and two homologous domains, each with an Fe⁺ᵌ-binding site. ⊳ synthesized mainly in the liver ⊳ Transferrin reversibly binds two ferric (Fe⁺ᵌ) ions with high affinity at physiologic pH but lower affinity at decreased pH, which allows release of iron in intracellular compartments. ⊳ After cellular delivery of iron via receptor mediated endocytosis, apotransferrin is recycled back into the circulation. 28 29 β2-Microglobulin  β2-Microglobulin is a small protein with a molecular weight of 11.8 kDa. It is the noncovalently bound light chain subunit of class I major histocompatibility complex MHC molecules present on the surface of all nucleated cells. BMG is shed into the blood, particularly by B lymphocytes, and some tumor cells. Its small size allows efficient glomerular filtration, resulting in a plasma half-life of approximately 100 minutes. Thank you 32