- •Introduction into biochemistry
- •General properties
- •Classification of proteins
- •Simple Proteins – representatives, properties and role
- •Globulins [g]
- •Histones (h) h are basic non value proteins. Localized in nucleus with mol. Mass (mm) 10000-20000 d. They contain of 30% diaminomonocarboxylic acids and have positive charge. Their iep is equal 10.
- •Table 1 “The properties of globular simple proteins”
- •Conjugated proteins
- •Table 2 Composition of the free (transport) lipoproteins in plasma of human
- •True gp Proteoglycans
- •Table 3 Chemical nature of glycosaminoglycans
- •Nucleoproteins (np)
- •Mononucleotides
- •Table 4 The composition and names of nucleosides, nucleotides and their phosphoric derivatives
- •Structure of dna Primary st. Of dna is a spirally one polynucleotides chain (pnc), the disposition of nucleotides in which determine all hereditary properties of organism.
- •Structure of rna
- •Enzymes
- •Mechanism of enzyme action
- •Factors influencing on enzyme activity
- •Enzyme inhibition
- •Classification of enzymes
- •III. Hydrolases
- •Bioenergetics
- •Table 6 Redox potential (rp)
- •Inhibition of oxidative phosphorylation.
- •The types of oxidation
- •Peroxidase’s type
- •Vitamins
- •Vitamin b12
- •Ascorbic acid (vitamin c)
- •Rutin, vitamin p (permeability) – bioflavonoids, capillaris’s strengthening
- •Fat soluble vitamins
- •Deficiency diseases
- •Vitamin k
- •Carbohydrates metabolism. Digestion and absorption of carbohydrates. Intermediate metabolism of carbohydrates
- •Carbohydrates metabolism. Intermediate and final stages of carbohydrates metabolism
- •Lipids of food, their importance, digestion, absorption. Micelles and chylomicrons. The role of intestinal wall, liver, lungs and adipose tissue in lipid metabolism
- •Lipids metabolism. Lipoproteins, their composition and role. The pathways of usage of glycerol and free fatty acids in cells
- •“Pathologic chemistry of lipid’s metabolism”
- •The intermediate Metabolism of Simple Proteins (part 1): the conversion of amino acids in tissues. The formation and usage of Creatine. The decarboxylation of amino acids, the role of biogenic amines
- •Simple proteins metabolism. The pathways of formation and detoxification of ammonia
- •Conjugated proteins metabolism
- •Biochemistry of liver
- •Classification of hormones
- •General properties of hormones
- •Hormones of epiphysis Melatonin
- •Hypothalamic hormones
- •Vasopressin (antidiuretic hormone)
- •Oxytocin
- •Hormones of hypophysis
- •Hormones of pancreas
- •Hormones of adrenal glands
- •Sexual hormones are formed in gonads.
- •Estrogens
- •If the pregnancy beginns so development of embryo occurs; if the pregnancy doesn’t occur so degeneration of yellow body proceeds and mensis beginns again Androgens
- •Biochemistry of blood plasma
- •Table 10 a main biochemical indices in the blood plasma (serum)
- •Functions and diagnostic importance of some fractions of proteins Table 11 Biologic and clinic importance of blood serum proteins
- •Blood clotting system
- •Blood dissolution system
- •Complement system
- •Inorganic constituents of blood plasma. Water-mineral metabolism. Acidosis and alkalosis
- •Acidosis and alkalosis Table 12 Acidosis and alkalosis
- •Water metabolism
- •Biochemistry of erythrocytes
- •Metabolism in erythrocytes
- •The physiological and pathological derivatives of hemoglobin and their spectra of taking up
- •Biochemistry of white blood cells
- •Biochemistry of kidneys
- •Normal and pathologic constituents of urine. Urine analysis – its clinical significance Composition of normal urine
- •Physical examination
- •I. Volume
- •The term polyuria implies an increased volume of urine
- •II. Colour
- •III. Specific Gravity
- •Clinical significance
- •IV. Acidity and pH
- •Clinical Significance
- •V. Odor
- •Causes of abnormal odor
- •VI. Turbidity
- •Types of turbidities
- •Inorganic constituents
- •Chlorides
- •Clinical significance
- •Organic constituents
- •Clinical significance
- •II. Ammonia
- •Clinical significance
- •Increase
- •Uric acid
- •Clinical significance
- •Clinical aspect
- •Creatinine and creatine
- •Oxalic Acid
- •Clinical significance
- •Aminoacids
- •Aminoacidurias
- •Proteins
- •Proteinuria
- •Abnormal constituents
Classification of hormones
hormones – simple proteins (insulin, somatotropin)
hormones – conjugated proteins (thyreotropin)
hormones – polypeptides (glucagon)
hormones – derivatives of aminoacids (thyroxin, adrenaline, noradrenaline)
steroid hormones (corticosteroids, sex hormones)
hormones – derivatives of fatty acids (prostaglandines, prostacyclines)
It is known near 50 hormones.
General properties of hormones
Specificity of action. Every hormone has unique answer.
High biological activity – 1g of adrenaline activates the contraction of 100 million of hearts. Concentration of hormones in the blood 10-15 - 10-9 mol/L.
H-s are secreted by endocrine glands. Mechanism of secretion – exocytose.
The distance of action.
The short duration of action: the hormones are divided into two groups: 1) hormones of stress (action is continued from few minutes to few hours); 2) hormones of adaptation (the action is lasted 10-14 days).
H-s are in the blood, where they are bonded by proteins.
All hormones act through receptors. Receptors – acids big proteins, which has property specific to bond determinate hormones. Receptors recognize and select hormones on the gradient of concentration 10-6 – 10-7 . For hydrophilic hormones receptors are localizated on external side of membrane, for hydrophobic – inside cells. The cells, which have receptors for hormone are named target cells. The sensibility of cells to hormone depends on the quantity of receptors. The quantity of receptors for hormones fluctuate from 500-30000 (the quantity of receptors for hypotalamic-hypophyseal hormones is less than for peripheral hormones). The increasing of quantity of receptors leads to increasing of sensibility of cell to action of hormone, but if the quantity of hormones is increased too much, the sensibility of cell to action of hormone is decreased, because the formation of domains takes place. Domains are destroyed by immune system and they can not to joint with hormones. The defficiency symtomps of hormone are caused moistly different disturbance of receptors. Characteristic of receptors. Concentration – low (thousands) cells; the ability to bond of hormone – very high (10-11 – 10-9 mol/L); specificity – high; saturation – at physiologic concentration; the quantity of receptors is changed very rapidly
MECHANISMS OF ACTION
There are 3 kinds of mechanism of hormone action.
Membrane-cytosol mechanism. Receptors are on outside of membrane and hormone does not penentrate into cell. There are 3 signal systems for this mechanism – adenilatecyclase (cAMP), guanilatecyclase (cGMP) and calcium systems (inositol phosphate mechanism)
Adenylyl cyclase mechanism: hormones which act at this mechanism, bind with receptor which consists of 3 parts – proper receptor, intermediate protein G, catalytic part – enzyme adenylyl cyclase. When hormone joins to receptor, adenylyl cyclase is activated and transforms ATP to cAMP which activates proteinkinase A (PKA consists of two regulatory and two catalytic parts which form active center). During the activation process the PKA splits up and regulatory parts are eliminated with cyclic AMP. This causes the formation of active PKA, consisting of 2 catalytic parts. Protein kinase A phosphorylates proteins and enzymes of glycogenolysis, glycolysis, lipolysis, synthesis of proteins. This leads to the next physiologic effects: 1. Increase of power and rate of heart contraction; 2. Increase of arterial pressure; 3. Increase of glucose in blood plasma; 4. Increase of lipolysis and glycogenolysis; 5. Increase of ions transport through membranes; 6. Increase of biosynthesis of proteins. The vast majority of protein-peptide hormones acts through adenylyl cyclase.
Guanylyl cyclase mechanism: Receptors are located in memranes more deeply, catalytic part has guanylyl cyclase activity. Second messenger - cGMP which activates cGMP-dependent proteinkinase (PKG) which phosphorylates glycogensynthetase and some proteins. This leads to vasodilation and relaxation of muscles, increase of diuresis and promotes diarrhea. Through the cGMP act sodium-uretic factor (atriopeptide), bacterial toxins, NO
Calcium as second messenger: Concentration of calcium in cytosol is 0,1-10 mkmole/L
(10-7—10), extracellular concentration of calcium and concentration in cellular organelles are up to 5 mmole/L (10-3 - -4 ) more 5000-10000 times. Hormone interacts with receptor and causes the changes in G-protein. Activated G-protein stimulates Ca-channels and phospholipase C. Ca-channels are opened ans calcium enters the cell. Calcium binds with calmodulin, forming a complex which influences on some intracellular enzymes. For instance, Ca-calmodulin activates phosphodiesterase, proteinkinase C. proteinkinase C stimulates mitosis. Besides, Ca plays an important role in muscular contraction. Phosphatidylinositoldiphosphate of membranes is hydrolized by phospholipase C to DAG and inositoltriphosphate (ITP). DAG activates the proteinkinase C. ITP opens the endoplasmic reticulum and calcium releasing into cytosol. Growth hormone, lactotropin, adrenalin, noradrenalin act through calcium, ITP and DAG.
Second mechanism of hormone action – cytosol mechanism. Hormones which have a hydrophobic properties enter into cells and bind with intracellular receptor. Receptors can be located in cytosol and nucleus. Steroid and thyroid hormones act by this mechanism Hormone-receptor complex enters the nucleus and acts on some sites of DNA, causing expression of certain genes. There is another pathway of steroid hormones. Some steroid hormones pass through nuclear membrane and bind with intranuclear receptor. Thyroid hormones have a receptors in cytosol, but hormone-receptor complex breaks up in nucleus and hormone acts on DNA itself.
Third mechanism of hormone action – membrane mechanism. Hormones which act by this mechanism change permeability of membranes and concentration of metabolites in the cell. For instance, insulin, prolactin, somatotropin. Hormone interacts with receptor which is located on outer surface of membrane. This leads to changes in conformation of intramembrane protein associated with tyrosine kinase (TK). TK undergoes autophosphorylation and stimulates the phosphorylation of some intracellular proteins and enzymes (intracellular kinases and phosphatases). Intracellular kinases and phosphatases act on certain processes such as phosphorylation or dephosphorylation of intracellular proteins and enzymes. This results in increase of membrane permeability for glucose, proliferation and anabolic pathways such as glycogenogenesis, lipogenesis, liponeogenesis, protein biosynthesis. Catabolic processes decrease. For instance, glycogenolysis, protein cleavage (proteolysis), lipolysis. Some anabolic processes dicreases too, gluconeogenesis for example. Glycolysis is a catabolic pathway, but this process increases.