- insufficient intake of pancreatic lipase into intestine;
- the violation of bile intake into intestine;
- digestive tract diseases (damage of epithelium). Steatorrhea is observed.
Hyperlipoproteinemias. Primary hyper- and hypolipoproteinemias are due to genetic defects in lipoprotein metabolism and transport.
1. Hypercholesterolemia (concentration of LDL or HDL is risen). Familial hypercholesterolemia (β-lipoproteinemia) is connected to full or partial loss of liver ability to remove LDL from blood flow.
2.Hypertriacylglycerolemia(concentration of chylomicrons or VLDL is risen). It is observed in violation of processes of fat transport from blood into tissue when there is insufficient activity of blood lipoprotein lipase.
3. The admixed form.
Hyperlipoproteinemia is found approximately in every tenth person. It raises the probability of atherosclerosis.
Secondary (non-congenital) hyperlipoproteinemia arises in diabetes, hepatitis, chronic alcoholism.
Ketonemia and ketonuria.At starving or having diabetes the concentration of ketone bodies in blood can rise to 20 mmol/l (ketonemia). Ketonemia is usually accompanied by ketonuria. Normally about 40 mg of ketone bodies are excreted with urine daily, with diabetes it is up to 50 g and more.
Cholelithiasis (cholesterol gall stone disease).Stones are formed in the gall bladder or ducts as a result of sedimentation and crystallization of bile components. Cholesterol or bilirubin is main component of gall stones. Cholesterol stones are more common. They are formed when bile micelles are not capable to contain all cholesterol. Cholesterol sedimentation is promoted by bile stagnation, inflammatory diseases of gall bladder and ducts.
The surgical removal of gall stones is the main treatment now. Another method of treatment is also applied. It is using of chenodeoxycholic acid. Cholesterol solubility mostly depends on it; besides, it inhibits HMG-CoA-reductase. Not only cholesterol sedimentation is stopped, but dissolution of already available stones becomes possible.
Atherosclerosisis a chronic disease characterized by violation of lipid metabolism and accompanied by cholesterol accumulation in vessels in the form of atherosclerotic plaques.
Hypercholesterolemia is the main pathogenetic factor in atherosclerosis development. Primary damages of vascular endothelium have great importance (action of modified lipoproteins, hypertension, inflammatory processes, blood coagulation infringements, action of toxicants). Disease development is also influenced by hereditary predisposition. Diabetes mellitus, obesity, gout, cholelithiasis, insufficient physical activity, psycho-emotional stress can also promote the development of atherosclerosis.
Atherogenic lipoproteins are LDL and VLDL which have been exposed to peroxide oxidation. In an arterial wall they are ingested by macrophages. At first there is the formation of fatty streak, and then sclerosed plaques filled with cholesterol esters are formed. Calcification of plaques occurs. Deformations of vessels develop and narrowing of their lumen until obliteration occurs.
HDL are considered as antiatherogenic. They carry out "reverse" transport of cholesterol from peripheric tissues into liver where it is oxidized into bile acids. HDL detain peroxide modification of LDL and VLDL. The probability of disease is higher, the higher the concentration ratio of LDL to HDL in blood.
The most frequent complication of atherosclerosis is coronary heart disease.
Low cholesterol diet and using medicines increasing cholesterol excretion or inhibiting its synthesis are applied for the atherosclerosis treatment.
1. Give classification of lipids, specifying functions of each class of lipids in an organism.
2. Name structural components acting as hydrophobic and hydrophilic groups in lipids: phosphatidylethanolamine; sphingomyelin; cholesterol.
3. Name products formed during hydrolysis in intestine of the following compounds: 1-stearyl-2,3-dipalmityl-glycerol; 1-palmityl-2-oleyl-phosphatidylcholine.
4. What is the role of bile acids in digestion of lipids?
5. Give the sequence of reactions of triglycerides synthesis from fatty acids.
6. What stages are included by the process of β- oxidation of fatty acids? Where are these reactions localised?
7. During what process redused NADP necessary for the synthesis of higher fatty acids is formed?
8. In what organs cholesterol synthesis basically occurs?
9. Name the key enzyme of cholesterol synthesis.
10. Why hypercholesterolemia and not hypocholesterinemia more often occur?
11. How do we classify transport lipoproteins? Specify their functions.
12. How does the synthesis of unsaturated fatty acids occur?
13. Give the scheme of phospholipids breakdown under the influence of phospholipase.
14. What unsaturated acid is nesessary for the synthesis of eicosanoids?
15. What lipid metabolism violations are known to you?
16. Characterise the mechanism of atherosclerosis development.