1. Protein blood plasma

4. The total content of protein in blood plasma. The total contents of proteins in blood plasma is 65-85 g/l. The increase of protein level in blood is called hyperproteinemia and decrease – hypoproteinemia. In paper electrophoresis blood plasma proteins can be separated on 5 fractions: albumins (40-50 g/l),  1 -globulins (3-6 g/l),  2 -globulins (4-9 g/l),  -globulins (6-11 g/l),  -globulins (7-15 g/l).

5. Function of plasma proteins: 1.Nutrition and tissue formation. 2.Viscosity. The plasma proteins provide viscosity to the plasma. This helps in providing the resistance to blood flow in the cardio vascular system. 3. Osmotic pressure. Plasma albumin is more important in this respect and responsible for about 5O% of the total osmotic pressure exerted by plasma proteins.

6. Function of plasma proteins: 4. Carrier function Albumins transport bilirubin, certain hormones and drags, FFA. Lipoproteins carry lipids; ceruloplasmin and transferrin carry copper and Iron respectively. 5. Blood coagulation - fibrinogen. 6. Buffer action. 7. Immunity- resistance against infections. 8. Hormones - а large number of hormones are proteins in nature. 9. Enzymes- Most plasma enzymes are very important for diagnosing diseases.

7. Albumins Globulins Fibrinogen

10. Globulins  1 -globulins  1 -globulins – transport of lipids, thyroxin, corticosteroid hormones;  2 -globulins  2 -globulins - transport of lipids, copper ions;  -globulins  -globulins - transport of lipids, iron and protective (participation of  -globulins in immune reactions as antitoxins);  -globulins  -globulins as immunoglobulins functions.

11. Globulins The molecular weight of globulins is approximately 150000-300000. They also support the blood oncotic pressure and acid-alkaline balance, provide amino acids for the organism requirements. The globulin level in blood plasma is 20-40 g/l. A ratio between concentrations of albumins and globulins (so called “protein coefficient”) in blood plasma is often determined in clinical practice. In healthy people this coefficient is 1,5-2,0.

22. are the largest lipoproteins (180 to 500 nm in diameter) are synthesized in the ER of intestinal cells contain 85 % of TGs (it is the main transport form of dietary TGs). apoprotein B-48 (apo B-48) is the main protein component Chylomicrons

23. exocytosis Lymphatic vessel deliver TGs from the intestine (via lymph and blood) to tissues (muscle for energy, adipose for storage). bind to membrane-bound lipoprotein lipase (at adipose tissue and muscle), where the triacylglycerols are again degraded into free fatty acids and monoacylglycerol for transport into the tissue are present in blood only after feeding

24. VLDL are formed in the liver contain 50 % of TGs and 22 % of cholesterol two lipoproteins — apo B-100 and apo E the main transport form of TGs synthesized in the organism (liver) deliver the TGs from liver to peripheral tissue (muscle for energy, adipose for storage) bind to membrane-bound lipoprotein lipases (triacylglycerols are again degraded into free fatty acids and monoacylglycerol) Apo B Apo E triacylglycerol cholesteryl esters phospholipids cholesterol

25. Lipoproteinlipase – enzyme which is located within capillaries of muscles and adipose tissue Function: hydrolyses of TGs of chylomicrons and VLDL. Formed free fatty acids and glycerol pass into the cells Chylomicrons and VLDL which gave up TGs are called remnants of chylomicrons and remnants of VLDL Remnants are rich in cholesterol esters Remnants of chylomicrons are captured by liver Remnants of VLDL are also called intermediate density lipoproteins (IDL) Fate of the IDL: - some are taken by the liver - others are degraded to the low density lipoproteins (LDL) (by the removal of more triacylglycerol)

26. Metabolism of chylomicrons and VLDL

27. LDL LDL are formed in the blood from IDL and in liver from IDL (enzyme – liver lipase) LDL are enriched in cholesterol and cholesteryl esters (contain about 50 % of cholesterol) Protein component - apo B-100 LDL is the major carrier of cholesterol (transport cholesterol to peripheral tissue)

28. Cells of all organs have LDL receptors Receptors for LDL are localized in specialized regions called coated pits, which contain a specialized protein called clathrin Apo B-100 on the surface of an LDL binds to the receptor Receptor-LDL complex enters the cell by endocytosis. Endocytic vesicle is formed

29. Vesicle fuse with lysosomes Lysosomal lipases and proteases degrade LDL LDL receptor itself returns to the plasma membrane Apo B-100 is hydrolyzed to amino acids Cholesteryl esters are hydrolyzed to free cholesterol and fatty acids Released free cholesterol: - is incorporated into the membranes or - is reesterified for storage inside the cell by the enzyme acyl CoA:cholesterol acyltransferase (ACAT) Feedback regulation: abundance of intracellular cholesterol suppresses the synthesis of LDL receptors and so the uptake of additional cholesterol from plasma LDL is blocked

30. LDL uptake by receptor-mediated endocytosis

31.  congenital disease when LDL receptor are not synthesized (mutation at a single autosomal locus)  the concentration of cholesterol in blood markedly increases  severe atherosclerosis is developed (deposition of cholesterol in arteries)  nodules of cholesterol called xanthomas are prominent in skin and tendons  most homozygotes die of coronary artery disease in childhood  the disease in heterozygotes (1 in 500 people) has a milder and more variable clinical course Familial hypercholesterolemia atherosclerosis xanthomas

32. Cholesterol deposits in the eyelids (xanthelasmas) Xanthomas Xanthomas around the corneaXanthomas

33. HDL  are formed in the liver and partially in small intestine  contain the great amount of proteins (about 40 %)  pick up the cholesterol from peripheral tissue, chylomicrons and VLDL  enzyme acyltransferase in HDL esterifies cholesterols, convert it to cholesterol esters and transport to the liver

34. High serum levels of cholesterol cause disease and death by contributing to development of atherosclerosis Cholesterol which is present in the form of the LDL is so-called "bad cholesterol." Cholesterol in the form of HDL is referred to as "good cholesterol” HDL functions as a shuttle that moves cholesterol throughout the body

35. The ratio of cholesterol in the form of LDL to that in the form of HDL can be used to evaluate susceptibility to the development of atherosclerosis LDL/HDL Ratio For a healthy person, the LDL/HDL ratio is 3.5

36. precursor of fibrin the structural element of blood clots fibrinogen participates in blood clotting and thus prevents the loss of blood from the vascular system of vertebrates the approximate molecular weight of fibrinogen is 340000 it is the complex protein, it contains the carbohydrate as prosthetic group. The content of firinogen in blood is 3-4 g/l. Fibrinogen

37. Ig A, Ig G, Ig E, Ig M - proteins of  -globulin fraction of blood plasma executing the functions of antibodies which are the main effectors of humoral immunity. Immunoglobulins Molecules of immunoglobulins are glycoproteins. The protein part of immunoglobulins contain four polipeptide chains: two heavy H-chains and two light L- chains.

38.  -fraction glycoprotein In blood plasma of healthy people the C-reactive protein is absent but it occurs at pathological states accompanied by an inflammation and necrosis of tissues. The availability of C-reactive protein is characteristic for the acute period of diseases – “protein of an acute phase”. The determination of C-reactive protein has diagnostic value in an acute phase of rheumatic disease, at a myocardial infarction, pneumococcal, streptococcal, staphylococcal infections. C-reactive protein

40. Some function of plasma proteins

41. PROTEINSConditions by which change amounts of proteins decreaseincrease Acidic alpha-1 glicoprotein of cancer tumors Chronic inflammations, (rheumatoid arthritis) Prothrombinin diseases of the liver CeruloplasminBy disease Vilson's Konovalow'sin pregnancy alpha antythrobininfringement of functions of liverby in inflammations alpha antythrombinin infringement of functions of the liver alpha 2- macroglobulinin diabetes, disease of 1iver,nephrotic syndrome cholesterasein disease of liver, hypothyroidism, burns traumatic shock, operation, heart attack, bronchial asthma Haptoglabin.inflammation, infections, fiver, cancer TransferrinCancer of the liver C reactive proteinAcute infections / acute phase of inflammations Beta lipoproteins or LDL'obstucative jaundice, 'hypothyroidism, atherosclerosis, Changes of amounts several proteins of plasma of blood by definite pathological conditions

42. The enzymes, which determines in definite disease for diagnoses ENZYMES INCREASE 1. AST aspartataminenotrasferase 2. ALT alanineaminotransferase 3. LDH1 and LDH2 lactate dehydrogenase 4. LDH5, LDH4 5. LDH2, LDH3, LDH4 6. CPK, creatinphosphokinase 7. Alcaline Phosphates 8. Acidic phosphates 9. alpha amylase in myocardial infarction (organospecific enzyme-liver) Hepatopathology ( heart) in myocardial infraction 1iver bronchitis, pneumonia damage of muscular tissues rickets Pancreatitis

43. Hypoproteinemia - decrease of the total contents of proteins in blood plasma. This state occurs in old people as well as in pathological states accompanying with the oppressing of protein synthesis (liver diseases) and activation of decomposition of tissue proteins (starvation, hard infectious diseases, state after hard trauma and operations, cancer). Hypoproteinemia (hypoalbuminemia) also occurs in kidney diseases, when the increased excretion of proteins via the urine takes place. Hyperproteinemia - increase of the total contents of proteins in blood plasma. There are two types of hyperproteinemia - absolute and relative. Absolute hyperproteinemia – accumulation of the proteins in blood. It occurs in infection and inflammatory diseases (hyperproduction of immunoglobulins), rheumatic diseases (hyperproduction of C-reactive protein), some malignant tumors (myeloma) and others. Relative hyperproteinemia – the increase of the protein concentration but not the absolute amount of proteins. It occurs when organism loses water (diarrhea, vomiting, fever, intensive physical activity etc.). Causes and consequences of protein content changes in blood plasma