Plasma proteins Vladimíra Kvasnicová Plasma proteins • include proteins of blood plasma and proteins of interstitial fluid Distribution in body fluids • continual movement from blood vesels to intersticium • transport by pinocytosis and through interendothelial junctions • capillary basal membrane molecular sieve molecule size dependent passage through protein Mr intravascular (x 103) albumin 66 (%) 42 transferrin 80 32 haptoglobin 1-1 85 50 IgG 144 44 IgA 160 41 haptoglobin 2-2 160 75 2-macroglobulin 720 92 IgM 971 77 (accepted from book: Clinical Laboratory Diagnostics / Lothar Thomas) Proteins of interstitial fluid • subcutaneous: albumin • lymph: less proteins than in plasma • liquor: 200x less than in plasma • patological fluids: transsudate exsudate < 30 g/l > 30 g/l Plasma proteins • include proteins of blood plasma and proteins of interstitial fluid • almost all are glycoproteins • some groups of proteins are classified separatelly (enzymes, proteohormones) • „total protein“ ~ more than 300 proteins Individual proteins of blood plasma The figure is from http://www.beckmancoulter.com/products/instrument/protein/proteomelab_igy_dcr.asp (Feb 2007) • proteins are ampholytes: -COOH -COO- + H+ -NH2 + H+ -NH3+ they are negatively charged under physiological pH ANIONS Common functions of plasma proteins • buffer properties (maintenance of pH) • maintenance of oncotic pressure of blood • some transport proteins have an antioxidant function Classification of plasma proteins • by electrophoretic mobility prealbumins albumin alpha, beta and gama-globulins fibrinogen The figure is from textbook: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2 The figure is from textbook: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2 Principal proteins of each fraction immunoglobulins: IgG, IgA, IgM 2-macroglobulin haptoglobin 1-antitrypsin transferrin orosomucoid C3-complement Position of lipoproteins in electrophoretic patern The figure is from: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2 • by specific function transport proteins proteins of immune system system of proteases and antiproteases proteins of hemocoagulation system signal proteins enzymes cellular proteins • by clinical use cardiomarkers tumormarkers acute phase reactants cellular enzymes hormones cytokines Factors influencing concentration of proteins total protein: 64 – 83 g/l • velocity of synthesis and degradation • distribution in body fluids • loss into the third place • elimination from the body • hydration of the body other important factors: • elevation of concentration before taking blood sample body position ( in supine position) tightening of arm • storage of biological speciment Consequences of abnormal concentrations • change in sedimentation of erytrocytes • swelling • polyuria • increased sensitivity to infections Physiological variability • increased concentrations plasma > serum (fibrinogen) stand-up position (by 10-15 %) increased muscle activity (by 12 %) dehydration • decreased concentrations children, pregnant women after starvation (albumin, transferrin, C3) Location of synthesis • liver most of plasma proteins • plasmocytes • other cells immunoglobulins e.g. 2-microglobulin 25 g are synthesized and produced daily Regulation of synthesis INCREASE inflammation hypertyroidism hypercotizolism grows hormone irron deficiency protein loss clonal production of Ig DECREASE liver damage with parench. tissue nutritional deficit hypotyroidism diabetes mellitus alcoholism Regulation of synthesis INCREASE inflammation hypertyroidism hypercotizolism grows hormone irron deficiency protein loss clonal production of Ig DECREASE liver damage with parench. tissue nutritional deficit hypotyroidism diabetes mellitus alcoholism Catabolism of proteins location liver kidneys endotelial cells other cells course desialization of glycoproteins pinocytosis hydrolysis in lysosomes use of amino acids Catabolism of proteins location liver kidneys endotelial cells other cells course desialization of glycoproteins pinocytosis hydrolysis in lysosomes use of amino acids • catabolism can be influenced by increased sialization of glycoproteins target receptors defect DECREASE IN CATABOLISM OF PROTEINS • velocity of the catabolism is described by BIOLOGICAL HALF-LIFE HALF-LIFE of plasma proteins • is related to function of a protein the longest: structural proteins the smallest: regulatory proteins • it is influenced by distribution velocity of catabolism and elimination USE IN DIAGNOSTICS Elimination from organism • filtration in the kidneys excretion with urine physilogical loss: < 150 mg/day • diffusion into gastrointestinal tract hydrolysis or excretion with feaces • loss with skin KNOWLEDGE of protein properties laboratory determination metabolism and function distribution and half-life use in diagnostics correct interpretation http://www.sebia-usa.com/products/reagents.html (Feb 2007)