- •Биологическая химия
- •060101 – Лечебное дело
- •Часть II
- •Contents
- •Cholesterol
- •I. Theoretical part
- •1. Lipids metabolism
- •1.1. Classification of lipids
- •2. Glycolipids (basically glycosphingolipids).
- •Galactosyl ceramide
- •1.2. Digestion and absorption of fats
- •Lipolysis of triglycerides in adipose tissue
- •1.3. Fatty acids oxidation
- •2. Transport of fa inside mitochondrion.
- •3 Ketocyl CoA tyolase Palmitic acid preformed rest Palmityl-CoA Acetyl-CoA
- •Oxidation of unsaturated fatty acids
- •Violations of fatty acids oxidation
- •Acetyl-CoA metabolism
- •1.4. Lipogenesis
- •Regulation of fatty acids synthesis and break down
- •1.5. Metabolism of phospholipids
- •1.6. Essencial fatty acids. Eicosanoids
- •1.7. Cholesterol metabolism
- •Distribution and functions of cholesterol
- •Cholesterol biosynthesis
- •1. Conversion of active acetate into mevalonic acid.
- •2. Squalene formation from mevalonic acid.
- •Regulation of cholesterol synthesis
- •Cholesterol esters metabolism
- •Synthesis of bile acids
- •1.8. Regulation of lipid metabolism
- •1.9. Violations of lipid metabolism
- •Violation of fats adsorption processes:
- •Test questions
- •2. Proteins metabolism
- •2.1. Pathways of proteins degradation
- •2. Digestion of proteins.
- •The selectivity of peptidases
- •2.2. Amino acids metabolism
- •The reactions of amino groups
- •Intramolecular deamination.
- •Reactions of the carboxyl group
- •2. Aminoacyladenylate formation.
- •2.3. Ammonia neutralization in the body
- •Storage and transport of ammonia
- •Fumarate pyruvate aspartate
- •2.4. Violations of nitrogen metabolism
- •2.5. Metabolism of individual amino acids
- •2. Metabolism of sulfur amino acids.
- •3. Metabolism of branched chain amino acids.
- •Leu, Ile, Val α-keto acids acyl-CoA derivatives
- •4. Metabolism of dicarboxylic amino acids
- •5. Metabolism of diaminomonocarboxylic acids.
- •6. Metabolism of phenylalanine and tyrosine.
- •7. Metabolism of tryptophan.
- •2.6. Metabolism of conjugated proteins. Chromoproteins metabolism
- •The degradation of hemoglobin in the tissues (the formation of bile pigments)
- •The hemoglobin biosynthesis
- •2.7. Nucleoproteins metabolism
- •Adenine hypoxanthine; guanine xanthine
- •The synthesis of pyrimidine nucleotides u, c, t
- •I nosine-5'-phosphate Xantosine-5'-phosphate
- •The synthesis of deoxyribonucleotides
- •Test questions
- •3. Template biosynthesis
- •3.1. Biosynthesis of nucleic acids
- •3.1.1. Dna biosynthesis (replication)
- •Synthesis of dna in the rna template
- •3.1.2. Rna biosynthesis
- •Rna synthesis in rna template
- •3.2. Protein biosynthesis
- •The properties of the genetic code
- •Preparatory stage of protein synthesis
- •3.2.1. Translation
- •1. Initiation.
- •2. Elongation.
- •3.2.2. Post-translational modification of proteins
- •Transport of synthesized proteins through membranes
- •3.2.3. Regulation of protein biosynthesis
- •3.3. Genetic engineering
- •Test questions
- •4. Hormones, nomenclature, classification
- •Test questions
- •5. Metabolic processes interaction
- •In the organism
- •Protein and carbohydrate metabolisms interconnection
- •Protein and lipid metabolisms interconnection
- •Carbohydrate and lipid metabolisms interconnection
- •Levels of homeostasis regulation
- •Changes in metabolism during starvation
- •Test questions
- •6. Mineral and water and salt metabolism
- •6.1. Water in the human body
- •6.2. Salt metabolism
- •7. Renal biochemistry. The role of the kidneys in the regulation of water and salt metabolism
- •7.1. Excretory function of the kidneys
- •7.2. Homeostatic function of the kidneys
- •7.3. Metabolic functions of the kidneys
- •7.4. Regulation of water and salt metabolism and uropoiesis
- •Test Questions
- •8. Biochemistry of nervous tissue
- •8.1. Features of metabolism of nervous tissue
- •8.2. Mechanism of nerve impulses conduction
- •Cholinergic synapses
- •Test Questions
- •9. Biochemistry of muscle tissue
- •9.1. Chemical composition of muscle tissue
- •Sources of energy for muscle work
- •9.2. Mechanism of muscle contraction and its regulation
- •9.3. Biochemical changes in muscles within pathology
- •Test Questions
- •10. Biochemistry of extracellular matrix
- •10.1. Structure of extracellular matrix
- •Collagens.
- •Fibril-forming collagens
- •Collagen, forming a tela
- •10.2. Features of metabolism of extracellular matrix Catabolism of extracellular matrix proteins
- •Reparation of damage of the extracellular matrix in norm
- •Biochemical changes of connective tissue with aging
- •The lesions of connective tissue
- •11. Blood biochemistry
- •11.1. Respiratory function of blood. Buffer systems of blood
- •11.2. Blood coagulation system. Changes in pathology
- •Extrinsic and intrinsic pathways of blood clotting
- •Test Questions
- •12. Liver biochemistry
- •12.1. Main functions of the liver
- •The role of the liver in the metabolism of carbohydrates
- •The role of liver in lipid metabolism
- •The role of the liver in the metabolism of proteins and amino acids
- •12.2. Choleresis. Pigment metabolism. Types of jaundice
- •The cleavage of hemoglobin: hemoglobinverdoglobinbiliverdinbilirubin.
- •12.3. Detoxifying liver function
- •Test Questions
- •13. Regulation of calcium and phosphorus metabolism
- •14. Bone biochemistry
- •Test Questions
- •II. Laboratory workshop Laboratory work 1. Lipid metabolism
- •Hydrolysis of milk fat by lipase
- •Test Questions
- •Laboratory work 2. Phospholipids. Cholesterol
- •4.1. Schiff reaction.
- •4.2. Salkowski reaction.
- •4.3. Lieberman-Burchard reaction.
- •Preparation of solutions of cholesterol for the calibration curve
- •Test Questions
- •Laboratory work 3. Digestion of proteins. Determination of acids of gastric contents
- •Experiment 2. Qualitative determination of free hydrochloric acid in gastric juice using indicator congo red.
- •Results of the determination of gastric acidity
- •Test Questions
- •Laboratory work 4. The end products of nitrogen metabolism
- •Test Questions
- •Laboratory work 5. Hormones
- •2.1. Biuretic reaction.
- •2.2. Millon’s reaction.
- •2.4. Geller’s test.
- •3. Qualitative reaction to thyroxine.
- •4. Qualitative reactions to the 11-dehydro-17-oxykortikosteron (cortisone).
- •4.1. The reaction with phenylhydrazine sulfate.
- •4.2. The reaction with Fehling's reagent.
- •Test Questions
- •Laboratory work 6. Mineral and water and salt metabolism
- •1.1. Determination the pH of saliva.
- •1.2. Detection of phosphates in saliva.
- •2.1. Qualitative detection of chlorides in the urine.
- •2.2. Detection of calcium in the urine.
- •2.3. Detection of phosphates in the urine.
- •The composition of mixtures for the calibration curve
- •Test Questions
- •Laboratory work 7. Urine biochemistry
- •3.1. Qualitative detection and quantitative determination of protein in the urine.
- •3.1.1. The test by boiling in weak acid environment.
- •3.1.2. The test by boiling in an acid medium in the presence of saturated sodium chloride solution.
- •3.1.3. Geller’s test.
- •3.1.4. The test with sulfosalicylic acid.
- •3.1.5. Quantitative determination of protein in the urine by the method of dilution (Brandberg - Roberts - Stolnikov method).
- •Determination of protein in the urine using dilution method
- •3.2. Semi-quantitative method for determining glucose and ketone bodies in urine using test strips.
- •3.3. Detection of blood pigments in the urine by boiling with alkali (Geller’s test).
- •Test Questions
- •Laboratory 8. Blood biochemistry
- •1. Buffer properties of blood serum.
- •2. Quantitative determination of total protein in serum according to biuretic reaction.
- •The composition of mixtures for the ployying of the calibration curve
- •3. Determination of calcium in serum by the method of de Waard.
- •Test Questions
- •Laboratory work 9. Detection of bile pigments in urine
- •Test Questions
- •Laboratory work 10. Biochemistry of bone and connective tissue
- •1. Preparation of extracts of bone and teeth tissues.
- •Test Questions
- •Bibliography
- •Biochemistry
- •In Two Parts Part II
- •392008, Г. Тамбов, ул. Советская, 190г
1.8. Regulation of lipid metabolism
Lipid metabolism is controlled by CNS. The long negative emotional stress can cause considerable weight loss. Adrenaline and noradrenaline increase the activity of tissue lipase and the rate of lipolysis in adipose tissues; the amount of fatty acids in blood plasma increases as a result. The effect of glucagon on lipolytic system is similar to catecholamins.
Insulin has the opposite to adrenaline and glucagon action on lipolysis and mobilization of fatty acids.
Somatotropin stimulates lipolysis inducing the synthesis of adenylatecyclase. Hypofunction of the pituitary gland results in the deposition of body fat (pituitary obesity).
Thyroxine and sex hormones, also affect lipid metabolism. Removal of sex glands in animals causes excessive fat deposition.
1.9. Violations of lipid metabolism
Violation of fats adsorption processes:
- 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.
Atherosclerosis is 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.