Presentation on theme: "Water H2OH2O O H H 105 o bent molecule non-bonding electron pairs polar character O H H - + -- ++ ++ electrical dipole."— Presentation transcript:
Water H2OH2O O H H 105 o bent molecule non-bonding electron pairs polar character O H H - + -- ++ ++ electrical dipole
Hydrogen bonding - + - + - + - + - + 0 o C 3.6 / H 2 O H bonds - much weaker than covalent bonds ! bond energy of H-bonds in liquid water: about 19 kJ/mol ( covalent H – O bond in water: 460 kJ/mol ) water is most dense at 3.98 °C !!! (when freezing, ice will form first on the surface) attractions between water molecules HIGH melting point boiling point specific heat heat of vaporization surface tension
Attraction between water dipoles and ions "hydrated ions" WATER - very good solvent ! Dispersing "amphipathic" molecules "micelles"
"Amphipathic" molecules – contain both highly hydrophobic and highly polar groups palmitic acid non-polar chain = hydrophobic polar group = hydrophilic (water-loving) (water-fearing) Phospholipids phosphatidylcholine (lecithin) polar groups
Biological membranes - separate the cells separate the spaces (compartments) of the cell nucleus endoplasmic reticulum lysosome mitochondria cell membrane Phospholipid BILAYER hydrophobic hydrophilic
Water in human body ~ 60 % of the body weight intracellular ~ 40 % extracellular ~ 20 % PLASMA 5 % interstitial fluid 15 % - a very complex solution of inorganic & organic components K + Na + Mg 2+ Phosphates Proteins Na + K + Ca 2+ Mg 2+ Cl - HCO 3 - Phosphates Na + /K + pump ( = Na + /K + -ATPase ) Na + K+K+
Water balance Intake: ~ 1.5 - 2.0 l / day metabolic water (produced in human body by oxidation of food) 0.3 – 0.5 l /day Resorption: stomach, small intestine, LARGE INTESTINE Secretion: Saliva1 500 ml / day Stomach2 500 Bile 500 8 200 ml /day Pancreas 700 Small intestine3 000 Excretion:Urine60 % Skin20 % (perspiration) Lungs15 % Faeces 5 %
mmol/l Na + 132 – 145 K+K+ 3.8 - 5.2 Ca*2.1 – 2.6 Mg 2+ 0.8 – 1.1 Cl - 97 – 108 HCO 3 - 22 – 26 Phosphates HPO 4 2- + H 2 PO 4 - 0.6 – 1.6 Human blood plasma pH = 7.36 – 7.44 * Ca "total Ca" Ca 2+ "ionized" is about ½ of "total" ~ 1.2 mmol/l
phospholipids cholesterol PROTEINS - enzymes - receptors - transport systems SELECTIVE permeability (membrane = barrier) The flow of molecules and ions between the cell and environment is precisely regulated by SPECIFIC TRANSPORT SYSTEMS They regulate cell volume, ionic composition, pH They concentrate metabolic fuels and building blocks from the environment The extrude toxic substances They generate IONIC GRADIENTS essential for the excitability
Transport across membrane 1) Passive transport- does not involve energy - diffusion from high to low concentration 2) Active transport - uses energy (ATP) - can transport against the concentration gradient - one direction, high specificity 3) Secondary active transport - no direct need of energy - gradient created by active transport is used ! ATP "pumps" "channels"
Passive transport 1 2 3 1) Simple diffusionsmall molecule, NO charge, solubility in lipids ! O 2 CO 2 2) Ion channels - pore-forming proteins - can be "GATED" 3) Facilitated diffusion ("carrier proteins") - selective ! - large molecules, insoluble in lipids "gate" is open "gate" is closed concentration and electrochemical GRADIENT toward equilibrium
Ion transport antibiotics Gramicidin- peptide: 15 amino acids HELIX - hydrophilic groups inside "wet channel" - lipophilic groups outside "wide wet pore" increase of the permeability of bacterial cell wall inorganic ions can travel through equilibration of concentrations = NO GRADIENT
Valinomycin hydrophillic groups INSIDE = "WET cave" equilibration of K + concentration = NO GRADIENT hydrophobic (lipophillic) groups OUTSIDE ( = soluble in lipids of membrane) K+K+ highly selective carrier for K + ( Na + with water coating is too big) K+K+ K+K+
Valinomycin hydrophillic groups hydrophobic (lipophillic) groups
Active transport = "PUMPS" ATP ADP + P i Transport against GRADIENT ENERGY ! 3 Na + 2 K + ATP Na + /K + ATPase (sodium potassium pump) INHIBITION: cardiotonic steroids
Na + /K + ATPase in cell membrane of EVERY human cell ! electrogenic = transfers 3 Na + out and ONLY 2 K + into the cell inner side of the membrane - outer side of the membrane + inhibitors of this pump: cardiotonic steroids = cardiac glykosides (oubain, digoxin) treatment of heart failure, cardiac arrhytmia Digitalis purpurea (foxglove)
H + /K + ATPase stomach gastric acid HCl * carboanhydrase Zn 2+ CO 2 CO 2 + H 2 O HCO 3 - HCO 3 - + H + H 2 CO 3 K+K+ H+H+ ATP Cl - * parietal cell blood pH = 7.4 lumen of the stomach pH = 1 - 2 10 6 increase of H + concentration !
Secondary active transport "COTRANSPORT" Na + dependent transport of glucose, aminoacids, Ca 2+ "energy" = Na + gradient generated by Na + /K + ATPase SYMPORT ANTIPORT Na + glucose Na + Ca 2+
Na + - glucose symport Na + K+K+ glucose Na + ATP proximal tubulus of each nephron in the kidneys resorption of glucose intestines resorption of glucose from GI tract
Na + /Ca 2+ antiport = sodium–calcium EXCHANGER Na + K+K+ Ca 2+ Na + ATP Ca 2+ ATPase Na + /Ca 2+ exchanger very low concentration of Ca 2+ in cytosol
Endocytosis Large (polar) molecules – cannot pass through the hydrophobic membrane phagocytosis - cell ingests large object such as bacteria pinocytosis - uptake of solutes and molecules such as proteins receptor-mediated endocytosis – specific ! LDL receptor chylomicron remnant receptor receptors that mediates endocytosis of blood plasma lipoproteins cell absorbs material by engulfing it with its own membrane
Exocytosis = the opposite of endocytosis Exocytosis is needed for: - secretion of large molecules from cells: glands peptide hormones B cells antibodies - neuronal chemical synapses: realease of the neurotransmitter vesicles with neurotransmitter synaptic cleft receptor
Water transport across membranes high osmolality H2OH2O low osmolality Water moves by "simple diffusion" through membranes ? Additional mechanism for water transport: AQUAPORINS "water channels" Water transport - due to osmotic differences (osmotic gradient) OSMOSIS
The bioelements (summary) 1)Principal bioelements:O, C, N, H, P, S ( biomolecules: proteins, nucleic acids, lipids, saccharides ) 2)Water and ions ( H 2 O ) Na +, K +, Mg 2+, Ca 2+, Cl -, ( HCO 3 -, phosphates) 3)Mineral constituents of bones and teeth Ca PO 4 3- 4)Microelements (trace elements)Fe, Cu, Co, Zn, I, F, Se,... -------------------------------------------------------- 5)Contamination (intoxication):Hg, Al,...
Elements of group I I AI B H Hydrogenium Cu Cuprum Li Lithium Ag Argentum Na Natrium Au Aurum K Kalium Rb Cs Fr Alkali metals Alkali metals - very reactive - react with air O 2 and H 2 O - must be stored under oil
Hydrogen H biogenic element - it is present in almost all organic compounds ! H 2 O H + = proton ( H 3 O + ) pH = - log [H + ] The pH scale 0 7 14 acidic solutions alkaline (basic) sol. neutral
water is weakly ionized: H 2 O H + + OH - K W = [H + ] x [OH - ] = 10 -14 mol 2 / l 2 ionic product of water pH + pOH = 14 pure water: [H + ] = [OH - ] = 10 -7 mol/l pH = pOH = 7 ----------------------------------------------------------------------- Strong acids - fully ionised: monobasic acid: HCl H + + Cl - dibasic acid: H 2 SO 4 2 H + + SO 4 2- Weak acids – do not disociate completely: CH 3 COOH H + + CH 3 COO - Strong bases: NaOH, KOH, Ca(OH) 2 Weak base: NH 4 OH
human blood plasma: pH = 7.40 0.04 gastric juice: pH = 1 – 2 pancreatic juice: pH = ~ 8 ----------------------------------------------------- H + very low concentration in blood plasma !!! pH = 7.40 H + = 0.000 040 mmol/l (40 nmol/l) (Na + 142 mmol/l K + 4.5 mmol/l) extreme influence of H + on biological systems !!! ionisation of functional groups in PROTEINS Ionisation of amino acids + -
Lithium Li compounds: LiCl Li 2 CO 3 crimson (red) colour of flame Therapy of manic-depressive psychosis (bipolar affective disorder) = alternating periods of mania (euphoria) and depression The manic phase - increased activity, decresased need for sleep - persistent elevated mood - impaired normal functioning ! The depressive phase - lack of energy - pessimistic - self-destructive behavior (risk of suicide !) Li + changes of ion transport in CNS - still in use "mood stabilizing agent"
Lithium mineral water – therapy of GOUT (type of arthritis) (Li-urate more soluble than uric acid) Uric acid - in humans - the end product of purine catabolism - poorly soluble in water - lithium urate – more soluble !
Sodium Na (Natrium) Na + the main EXTRAcellular cation (132 – 145 mmol/l) Na + strongly binds water ionic diameter: Na + K + !!! in hydrated form: Na + larger in diameter than K + Na + ( together with Cl - ) large fraction of osmotic pressure (osmolality) of body fluids Water and Na balance are closely interdependent !
NaCldaily intake: 5 – 15 g food (common salt) Elimination: urine (95 %) sweat (perspiration) stool Kidney BLOOD Glomerular filtrate (180 l H 2 O / day) Glomerular filtration URINE 2 l H 2 O 5 – 15g NaCl [ 1.5 kg NaCl ] Tubular resorption dependent on hormones (aldosteron, ADH)
Hormones regulating tubular resorption Aldosteron- steroid hormone (mineralocorticoid) - produced in the adrenal gland (adrenal cortex) - acting in the distal tubule of the kidney nephron: reabsorption of Na + into blood secretion of K + into urine Vasopressin = antidiuretic hormone (ADH) - peptide hormone - synthesized in the hypothalamus, released into blood in the pituitary gland (posterior part) - ADH increases the permeability of the collecting duct to water allows water reabsorption small volume of concentrated urine deficiency of ADH: DIABETES INSIPIDUS - polyuria - excretion of large amounts of diluted urine ( 10 – 20 l /day !)
Potassium K (Kalium) K + the main INTRAcellular cation (cytosol > 100 mmol/l) -human blood plasma: only 3.8 - 5.2 mmol/l -daily intake: ~ 4g of KCl excretion: URINE -proper concentrations of K + and Na + functions of membranes „membrane potential“ most cells – membrane potential relatively stable neurons, muscle cells – use changes of membrane potential for function ! (nervous system – communication between neurons) action potential
3Na + cell membrane 2K + ATP ! Na + K+K+ EXTRAcellular fluid INTRAcellular fluid Na + /K + ATPase Ion channels ACTION POTENTIAL falling phase = repolarisation rising phase = depolarisation resting potential
In cells K + is bound to GLYCOGEN ! Diabetic coma ( glucose in blood ) Glycogen synthesis Binding of K + in cells Plasma K + depletion HEART failure !!! insulin
Copper Cu (Cuprum) microelement (in human body 100 - 150 mg) dietary intake: ~ 2 mg / day Cu 2+ - cofactor of some enzymes: cytochrom c oxidase (metalloenzymes) superoxide dismutase - cofactor of HEME biosynthesis CERULOPLASMIN - transport of Cu 2+ in blood plasma ( 8 Cu 2+ / mol. ) - 2 globulin synthesized in the liver - enzymatic activity: Fe 2+ Fe 3+ WILSON‘s DISEASE - accumulation of copper in tissues (hepatolenticular degeneration) - low ceruloplasmin levels - hereditary disease - neurological symptoms, liver disease
CuSO 4. 5 H 2 O copper (II) sulphate pentahydrate = „blue vitriol“ - in Fehling‘s solution (detection of glucose in urine) copper salts - poisonous ! ------------------------------------------- Hemocyanins - Cu 2+ containing proteins - O 2 transport - MOLLUSCA (snail, clam, mussel,...) - ARTHROPODA (crabs)
Silver Ag (Argentum) precious metal ( + H 2 S Ag 2 S black ! ) AgBr - photosensitive photography ------------------------------------------------------------------ Ag - useful in dental alloys for fittings and fillings ( Ag + Hg amalgam ) AgNO 3 - caustic effect treatment of warts Bartholin’s gland abscess in women (removal: silver nitrate stick insertion) - diluted solution: antiseptic properties it was dropped into newborn‘s eyes to prevent gonococcal conjuntivitis ! (Gonorrhoea is a venereal disease caused by the bacteria Neisseria gonorrhoeae)
Gold Au (Aurum) precious metal chemically and biologically resistent, inert in nature – almost exclusively in the native state pure gold – soft ! in jewellery: alloys (+ Cu, + Ag) harder The gold content of gold alloys in carats or in thousandths pure gold: 24 carats = 1000/1000 The standard for high quality jewellery: 18 carats = 750 / 1000 What is the gold content (g) of a 100 g piece marked 18 carats? 18 24 x 100g = 75 g
Elements of group II II AII B Be Beryllium Zn Zincum Mg Magnesium Cd Cadmium Ca Calcium Hg Hydrargyrum Ba Barium Sr Strontium Ra Alkaline earth metals
Magnesium Mg PLANTS: Mg 2+ - central atom of green pigment CHLOROPHYLL (photosynthesis) in human body: ~ 20 g Mg > ½ in bones ( Ca-Mg phosphates ) intracellular cation Mg 2+ activates number of enzymes !!! ENZYMES using ATP "kinases" glucose glucose–6–phosphate (Enzymes of ATP-dependent reactions require Mg 2+ as cofactor) hexokinase ATP ADP
other effects of Mg 2+ : anti-convulsive effect (MgSO 4 - prevention of eclamptic convulsions) influence on neuromuscular excitability can help to prevent kidney and gall stones "duodenal reflex" - MgSO 4 delivered into the region of the sphincter of Oddi relaxation of the sphincter + contraction of the gallbladder expulsion of bile to intestine ( the bile release from the gallbladder is stimulated by Mg 2+ ) Magnesium mineral water (Karlovy Vary) purgative effect
Calcium Ca CaO + H 2 O Ca(OH) 2 "slaking" slaked lime "burning" CaCO 3 limestone, chalk quicklime CaO + CO 2 Ca(OH) 2 + CO 2 CaCO 3 + H 2 O Hardening of mortar:
Calcium Ca in human body ~ 1 kg (99% in bones, teeth) dietary intake: 800 - 1200 mg / day human blood plasma: "total Ca" 2.5 mmol/l (extracellular !) ionized Ca 2+ 1.2 mmol/l resorption: ileum – specific protein carrier ~ 200 mg / day excretion: urine liver bile feces
Mineral constituents of bones and teeth enamel dentin cementum pulp Enamel: - hardest substance of the body water 1-3 % organic comp. 1% mineral > 95 % (bones ~ 60 %) F - fluoroapatite Hydroxyapatite Ca 5 (PO 4 ) 3 OH
Hormones regulating Ca metabolism Parathormone- peptide hormone ( 84 amino acids ) - secreted by parathyreoid glands - activation of bone mineral degradation Ca 2+ release from bones - stimulation of Ca 2+ readsorption in kidney - stimulation of calcitriol formation (kidneys) - stimulation of Ca-resorption protein formation (ileum) Ca 2+ in blood PTH
Calcitonin- peptide hormone ( 32 amino acids ) - produced by parafollicular cell of the thyreoid gland - inhibition of bone mineral degradation (decrease of „osteoclasts“ activity) - stimulation of Ca 2+ excretion in kidney Salmon calcitonin is used for the treatment of OSTEOPOROSIS Ca 2+ in blood
Calcitriol= 1,25-dihydroxycholecalciferol - active form of D–vitamin - stimulation of Ca-resorption protein formation absorption of calcium from the gastrointestinal tract
Ca 2+ increase PTH release inhibition Ca – FOOD (protein-bound) ILEUM Ca-resorption protein PLASMA Ca 2.5 mmol/l Ca 2+ 1.2 mmol/l URINE BONES PTH calcitonin calcitriol milk excrements
Very low concentration of Ca 2+ in cytoplasma 10 -6 mol/l MUSCLE - Ca 2+ is stored in sarcoplasmic reticulum (SR) CALSEQUESTRIN = calcium-binding protein of the SR 40 Ca 2+ binding sites Ca 2+ in cytoplasma can cause the specific action of the cell: MUSCLES contraction Ca 2+ = important SECOND MESSENGER
"SIGNAL" release of Ca 2+ EFFECT endoplasmic reticulum
Clotting of BLOOD Ca 2+ is required for the proper function of the coagulation CASCADE XaXa Fibrinogen Fibrin Prothrombin Thrombin Extrinsic pathway (Tissue factor pathway) Intrinsic pathway (Contact activation pathway)
Removing of Ca 2+ = NO clotting ! Anticoagulants - bind Ca 2+ ions ( "in vitro" = outside the body) Oxalate EDTA = ethylenediamine tetraacetic acid COO - COO + Ca 2+ Ca Citric acid
Gypsum, plaster of Paris CaSO 4. 2 H 2 O CaSO 4. 1/2 H 2 O + H 2 O hardening heating When the dry plaster powder is mixed with water, it re-forms into gypsum bandage impregnated with plaster = support for broken bones
Strontium Sr - similar to Ca 2+ incorporation in BONES (naturally present in bones in trace amounts) - new treatment for osteoporosis: „Strontium ranelate“ (improves bone density and strenght) excess: Strontium rickets radioisotope Sr bone marrow irradiation LEUKEMIA (important isotope regarding health impacts after the Chernobyl disaster) radioisotope Sr - treatment of bone cancer 90 89 half life 28 years half life 50 days
Barium Ba toxic heavy metal water-soluble compounds - strongly neurotoxic [ Ba(NO 3 ) 2 BaCl 2 ] - painful cramps, tremor BaSO 4 (barium sulphate) - almost insoluble in water ! - radiocontrast agent for X-ray imaging ( "barium meal" ) -imaging of the gastrointestinal tract large intestine
Zinc Zn (Zincum) microelement dietary intake: 12 -15 mg / day cofactor of many ENZYMES: carboxypeptidase - protein digestion carbonic anhydrase H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - alcohol dehydrogenase - oxidation of ethanol to acetaldehyde CH 3 CH 2 OH CH 3 CHO NAD + NADH+H +
Insulin binds ZINC ! "Zn – insulin hexamers" Metallothionein - protein synthesized in kidneys rich of -SH groups - can bind metals ( Zn 2+ Cd 2+.... ) - zinc transport, heavy metal detoxification (Hg 2+ ) ? Zinc is an essential nutrient for proper sperm production ! ------------------------------------------------ compounds used in medicine: ZnO - a basis of powders, pastes, creams ( in DERMATOLOGY ) dental fillings (cements): Zn 3 (PO 4 ) 2. 4 H 2 O"hopeit"
Cadmium Cd toxic heavy metal metallothionein – strongly binds Cd 2+ Cd intoxication kidney damage "Itai itai disease" - mass Cd poisoning in Japan in 1950 - the name comes from painful screams ( "itai" in Japanese = PAIN ) - the bones become soft and weak severe pain, fractures "Chemical castration" = destruction of seminiferous epithelium of testicles ( Zn 2+ antagonism )
Mercury Hg (Hydrargyrum) Toxic effects 1) elemental Hg - very toxic when absorbed as a vapour through lungs - poorly absorbed through the gastrointestinal tract !!! (only purgative effect) 2) inorganic Hg compounds HgCl 2 - "sublimate" - soluble in water = toxic - corrosive ulceration of GI tract - renal failure Hg 2 Cl 2 – "calomel" - low solubility = less toxic - it was used in medicine ! (diuretic and purgative effect, ointments in dermatology) - calomel electrod (reference electrod - measurement of pH)
2) organic Hg compounds - often extremely toxic - dimethylmercury Hg(CH 3 ) 2 damage of CNS (central nervous system) - one of the strongest known neurotoxins ! "The Minamata Disease" - mass Hg poisoning in Japan in 1956 - Minamata Bay – waste industrial water with Hg 2+ biomethylation by a variety of microorganism bioaccumulation in FISH dietary intake from fish diets Poison grain disaster in Iraq (1971) - seed grain mercury-treated to prevent rot was used as FOOD
Elements of group III III AIII B B Borum Sc Al Aluminium Y GaLa InAc Tl Ra
Boron B (Borum) PLANTS – micromineral Boric acid H 3 BO 3 - a very weak acid - disinfectant (used in dermatology and ophtalmology) - also toxic properties ! NH 3 + glutamate glutamine glutamine synthetase H 3 BO 3 = inhibitor toxic to BRAIN Sodium tetraborate Na 2 B 4 O 10 = borax (fusible glaze for pottery)
Aluminium Al in human body – only traces – contamination ? Al(OH) 3 together with MgO or Mg(OH) 2 oral antacid (neutralization of acid in the stomach) Al – also considered as toxic ACID RAIN SOIL release of Al 3+ !
Elements of group IV IV AIV B C Carboneum Ti Si Silicium Zr GeHf Sn Stannum Pb Plumbum
Carbon C (Carboneum) the most important biogenic element organic compounds (covalent bonds C-C, chains, rings) biomolecules: proteins, nucleic acids, lipids, carbohydrates combustion CO, CO 2 respiration CO 2 Toxic: CO competes with O 2 for hemoglobin HCN reaction with cytochromes inactivation of cell respiration
Silicon Si (Silicium) abundant element in lithosfere, but not useful in human body SiO 2 (silica)Quartz - common mineral in the Earth‘s crust - many varieties: amethyst (purple) citrine (yellow) morion (dark-brown) rose quartz (pink) - in many rocks (granit, sandstone), metallic ores cutting, breaking, crushing,... inhalation of fine SiO 2 dust SILICOSIS - lung disease occupational disease (miners, ceramics workers) progressive, signs of it will appear years after exposure !
Silicic acids: general formula n SiO 2. m H 2 O H 4 SiO 4 orthosilicic acid Silicates - salts of silicic acids SiO 4 4- Si atom - tetrahedral coordination by 4 oxygens complex structure - different degrees of "polymerization" linear arrangement FIBERS (asbestos) planar arrangement MICAS Silicate minerals - largest class of rock-forming minerals