The physiological and pathological derivatives of hemoglobin and their spectra of taking up

There are next physiological derivatives of hemoglobin: HbO2 (oxyhemoglobin) and HbCO2 (carbhemoglobin). Oxyhemoglobin has 2 dark lines in yellow-green part of spectrum. HbCO2 hasn’t got own spectrum because CO2 joins to globin of hb. Its spectrum is 1 line in yellow-green part of spectrum (as in Hb).

There are next pathological derivatives of Hb: HbCO (carboxyhemoglobin), methoxyhemoglobin (MtHb), glycosylated hemoglobin (Hb_Glc)

HbCO is formed under influence of CO. Its spectrum is 2 dark lines in yellow-green part of sun spectrum, but in comparison with HbO2 this hemoglobin isn’t reduced under influence of Stock’s reagent.

Methoxyhemoglobin is formed under action of oxidants. The 3-rd valency in iron of heme appears to which the OH group joins.its spectrum is 3 dark lines: 2 of them are in yellow-green part of sun spectrum and 1 line in red part of sun spectrum.

Glycosylated hemoglobin is formed due to binding of glucose to beta-chains of Hb. Formation of this hemoglobin occurs in long time hyperglycemia (more than 2-3 months), e.g in diabetes mellitus.

The pathological derivatives of hemoglobin are dangerous because they don’t function as transporters of oxygen and carbon dioxide.

Biochemistry of white blood cells

The peculiarities of metabolism in neutrophils

1. they have many lysosomes which contain proteinases such as collagenase, elastase, catepsin G and gelatinase

2. low level of oxidative phosphorylation that due to the lack of mitochondrions and high extent of glycolysis

3. high level of pentose phosphate’s cycle which gives NADPH2 used for formation of AFO

4. there is a specific enzyme myeloperoxidase that catalyzes the next reaction: H2O2 + H⁺ + Cl^-  HOCl (hypochloric acid) + H2O

5. they exrete defensive peptides consisting of 22-30amino acids

6. neutrophils have lysocyme (bactericidial agent)

7. neutrophils output the lactoferrin that is used for profilaxis of cancer and bacteriostatic agent

8. NADPH-oxydase is a specific enzyme that takes part in formation of AFO

9. Neutrophils output selectins and integrins

10. Neutrophils output activator of plasminogen (blood dissolution factor)

The role of neutrophils

They take part in acute inflammation response (AIR). AIR comprizes 3 stages:

1. Chemotaxis and adhesion

2. Respiratory explosion

3. Cleavage of antigenes

1 – chemotaxis is a gathering of neutrophils in inflammatory area. It occurs owing to selectins. Adhesion is a sticking of neutrophils to the vessels in inflammatory area due to the integrins

2 – respiratory explosion is an activation of all metabolic processes in neutrophils causing the distructruction of invaded antigenes. It accomplishes by migration of phagocytes from vessel and intensive formation of AFO

3 – cleavage of antigenes occurs due to proteinases of lysosomes

The concept of respiratory explosion

This phenomenon is characteristically for all phagocytes including neutrophils. Neutrophils are activated through specific reseptors which joined with G-protein and phospholipase C. the activation of Phospholipase C results in cleavage of phosphoinositoldiphosphate to inositoltriphosphate and DAG. ITP promotes releasing of calcium from endoplasmic reticulum. DAG activates protein kinase C that phosphorylates NADPH-oxydase. Beside of this the intake of calcium into cells from extracellular matrix occurs owing to G-Protein. Increase of calcium in cytosol of cells causes the assembleying of microtubules and actomyosin in neutrophils that results in migration of neutrophils to inflammatory area. The phosphorylation of NADPH-oxydase results in formation of AFO (see below). This accomplishes by intensive uptake of oxygen.

The formation of AFO

1. NADPH2 + 2O2 (under infl. Of NADPH-oxydase)  NADP + 2O2• + 2H⁺

2. 2O2• + 2H⁺ (under infl. Of SOD)  H2O2 + O2

3. H2O2 + O2•  •OH + ^-OH + O2

4. H2O2 + H⁺ + Cl^- (under infl. Of myeloperoxidase)  HOCl + H2O

5. Arg + NADPH2 + O2 (under infl. Of NO-synthase)  NADP + NO• + Citrulline + H2O

6. NO• + O2  ONOO• (peroxinitrite that influences on DNA and causes mutations)

The functions and biochemical peculiarities of basophils, eosinophils and monocytes

Basophils: 1) output heparin and histamine; 2) complex antigene-antibody causes the degranulation of basophils (this a way of participation of them in allergy)

Eosinophils: 1) uptake cocci; 2) detoxification of histamine; 3) destroying of toxins and immune complexes; 4) cytotoxic action that means killing of gelmints; 5) participation in allergy

Monocytes: they are converted to macrophages in tissues – 1) recognition of antigenes and formation of immune response; 2) monokins stimulate lymphocytes; 3) proteins of complement system destroy immune complexes; 4) output of blood dissolution factors

The peculiarities of chemical composition and metabolism of lymphocytes

Lymphocytes are divided into B-, T- and N-lymphocytes. B-lymphocytes output antibodies. T-lymphocytes are subdivided into T-killers, T-supressors and T-helpers. T-killers and N-lymphocytes causes the lysis of antigenes. T-supressors inhibit the immune response.T-helpers activate immune reactions.

Table 13 Peculiarities of white blood cells

Feature	B	T
Organells	Many	Few
RNA	Many	Few
DNA	Few	Many
Lipoproteins	Few	Many
Sialoproteins	Absent	Many
True glycoproteins	Many	Absent
Lipids	Many	Few

The peculiarities of metabolism of lymphocytes

1. glycolysis prevails in B-lymphocytes; aerobic oxidation of glucose occurs in T-lymphocytes

2. low level of beta-oxidation due to the lack of lipids in B-lymphocytes and enzymes of this process in T-lymphocytes

3. lymphocytes don’t synthesize glucose, FFA and Gln

4. Gln need for function of lymphocytes: glutamine is used in starvation by other tissues and there is a lack of its in the body. it results in decrease of immune reactions

5. Intensive purine’s metabolism

Biochemistry of muscular tissue

Muscular tissue consists of 80% of water and 20% of dry part. Dry part consists of 18-19% of organic compounds and 1-2% of inorganic compounds. Organic compounds are proteins and extractive substances. Proteins of muscles are divided into myofibrilar, sarcoplasmic, stroma’s and nucleoproteins. Extractive substances are divided into nitrogen-containing and nitrogenless substances. Nitrogenless substances are lipids, glycogen and products of their metabolism and creatine, creatinine, anserine, carnosine, adenylic system (ATP, ADP, AMP).

Anserine and carnosine take part in relaxation of muscles, maintain pH in muscles, antioxidants and activate ATP-ase’s activity of myosin.

Myofibrilar proteins make up 50-55% from all proteins of muscles. They’re divided into:

1. contractory (Myosin, actin, actomyosin, phosphorylated caldesmon in smooth muscles only)

2. relaxatory (titin, dephosphorylated caldesmon in smooth muscles only)

3. regulatory (tropomyosin (Tm), troponin (Tn), myosinbinding protein, alfa-actinin, nebulin

4. function of which is unknown (desmin, dystrophin)

Sarcoplasmic proteins make up 30-35% of total proteins of muscles. They’re divided into specific and non-specific. Specific proteins are myoglobin and calcineurin. Non-specific proteins are enzymes (e.g. aldolase), myoalbumins, myoglobulins.

Myoglobin consists of globin (1 chain from 153 amino acids) and heme like heme of hemoglobin. Myoglobin transfers oxygen in myocytes: Mgb + O2 ↔ MgbO2. Myoglobin is a storage of oxygen in muscles and pigment of them.

Stroma’s proteins are collagen and elastin (10% from all proteins of muscles) repeat, please, properties of these proteins, see theme 2 “Simple proteins”

Nucleoproteins repeat, please, composition of NP and formulas of heme, ATP, ADP, AMP, Creatine, Creatinine, Creatine phosphate, nucleotides

Chemical base of muscular contraction (schematically)

Nerve impulseacetylcholinecalcium release into synaptic spacecalcium enters the myocytecalcium binds with troponin which is constituent of triple complex – Tn-A-M, during this interaction Tn is released from this complex and interacts with tropomyosinactin and Myosin forms an active complex named actomyosin under influence of potassiumunder action of magnesium actomyosin complex cleaves ATP to ADP+inorganic phosphate, releasing energy released energy is used for muscular contraction. Thus, the ATP supplying underlies the process of muscular contraction

The pathways of resynthesis of ATP (should be repeated calculation of ATP and formulas of creatine kinase)

1) creatine kinase’s reaction

2) glucose

3) TAG

4) ketone bodies

5. amino acids

6. crush-way: adenylylkinase’s reaction: 2ADP↔ATP + AMP

The peculiarities of contraction of smooth muscles

4Ca-calmodulin dephosphorylated kinase of light chains of myosin  phosphorylated light chains of myosin  contraction

The relaxation of muscles

NO  cGMP PKGphosphorylated kinase of light chains of myosin (is inactive) dephosphorylated light chains of myosin relaxation

The peculiarities of myocardium

1. ketone bodies are main energetic source

2. creatine phosphate is a source of energy

3. aerobic glycolysis only