Water

H2O OH H105o

bent molecule

non-bonding electron pairs

polar character OH H

-

+

-

++

electrical dipole

Hydrogen bonding

-

+

-

+

-

+

-

+-

+

0 oC 3.6 / H2O

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

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+ Mg2+

Phosphates

Proteins

Na+ K+ Ca2+ Mg2+

Cl- HCO3- Phosphates

Na+/K+ pump ( = Na+/K+ -ATPase )

Na+

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: Saliva 1 500 ml / dayStomach 2 500Bile 500 8 200 ml /dayPancreas 700Small intestine 3 000

Excretion: Urine 60 %Skin 20 % (perspiration)Lungs 15 %Faeces 5 %

mmol/l

Na+ 132 – 145

K+ 3.8 - 5.2

Ca* 2.1 – 2.6

Mg2+ 0.8 – 1.1

Cl- 97 – 108

HCO3- 22 – 26

Phosphates

HPO42- + H2PO4

- 0.6 – 1.6

Human blood plasma

pH = 7.36 – 7.44 * Ca "total Ca" Ca2+ "ionized" is about ½ of "total" ~ 1.2 mmol/l

Blood plasma( extracellular fluid )

Cell fluid (cytosol)( intracellular fluid )

phospholipids

cholesterol

PROTEINS - enzymes

- receptors

- transport systemsSELECTIVE 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 diffusion small molecule, NO charge, solubility in lipids !

O2 CO2

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+highly selective carrier for K+

( Na+ with water coating is too big)

K+

K+

Valinomycin

hydrophillic groups

hydrophobic (lipophillic) groups

Active transport = "PUMPS"

ATP ADP + Pi

Transport against

GRADIENT

ENERGY !

3 Na+

2 K+

ATPNa+/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 Zn2+

CO2 CO2 + H2O

HCO3- HCO3

- + H+

H2CO3K+ H+

ATP

Cl-

Cl-

*

parietal cell blood pH = 7.4 lumen of the stomach

pH = 1 - 2

106 increase of H+ concentration !

Secondary active transport "COTRANSPORT"

Na+ dependent transport of glucose, aminoacids, Ca2+

"energy" = Na+ gradient generated by Na+/K+ ATPase

SYMPORT

ANTIPORT

Na+

glucose

Na+

Ca2+

Na+ - glucose symport

Na+

K+

glucose glucose

Na+

ATP

proximal tubulus of each nephron in the kidneys resorption of glucose

intestines resorption of glucose from GI tract

Na+/Ca2+ antiport = sodium–calcium EXCHANGER

Na+

K+

Ca2+ Ca2+

Na+

ATP

Ca2+ ATPase

Na+/Ca2+ exchanger very low concentration of Ca2+ 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 receptorreceptors 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 osmolalityH2O

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 ( H2O ) Na+, K+, Mg2+, Ca2+, Cl-, ( HCO3- , phosphates)

3) Mineral constituents of bones and teeth Ca

PO43-

4) Microelements (trace elements) Fe, Cu, Co, Zn, I, F, Se, ...

--------------------------------------------------------

5) Contamination (intoxication): Hg, Al, ...

Elements of group I

I A I 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 O2 and H2O

- must be stored under oil

Hydrogen H

biogenic element - it is present in almost all organic compounds !

H2O

H+ = proton ( H3O+ )

pH = - log [H+]

The pH scale

0 7 14 acidic solutions alkaline (basic) sol.

neutral

water is weakly ionized: H2O H+ + OH-

KW = [H+] x [OH-] = 10-14 mol2 / l2 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: H2SO4 2 H+ + SO42-

Weak acids – do not disociate completely: CH3COOH H+ + CH3COO-

Strong bases: NaOH, KOH, Ca(OH)2

Weak base: NH4OH

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 Li2CO3 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 !

N

N

NH

N

OH

OH

OH

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 !

NaCl daily intake: 5 – 15 g food (common salt)

Elimination: urine (95 %)

sweat (perspiration)

stool

Kidney

BLOOD Glomerular filtrate (180 l H2O / day)

Glomerular filtration

URINE

2 l H2O 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 bloodsecretion 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+

2K+

ATP !

Na+

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

Cu2+ - cofactor of some enzymes: cytochrom c oxidase (metalloenzymes) superoxide dismutase

- cofactor of HEME biosynthesis

CERULOPLASMIN - transport of Cu2+ in blood plasma ( 8 Cu2+ / mol. )

- 2 globulin synthesized in the liver - enzymatic activity: Fe2+ Fe3+

WILSON‘s DISEASE - accumulation of copper in tissues(hepatolenticular degeneration) - low ceruloplasmin levels

- hereditary disease - neurological symptoms, liver disease

CuSO4 . 5 H2O copper (II) sulphate pentahydrate

= „blue vitriol“

- in Fehling‘s solution (detection of glucose in urine)

copper salts - poisonous !

-------------------------------------------

Hemocyanins - Cu2+ containing proteins

- O2 transport - MOLLUSCA (snail, clam, mussel, ...)

- ARTHROPODA (crabs)

Silver Ag (Argentum)

precious metal ( + H2S Ag2S black ! )

AgBr - photosensitive photography

------------------------------------------------------------------

Ag - useful in dental alloys for fittings and fillings

( Ag + Hg amalgam )

AgNO3 - 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?

1824

x 100g = 75 g

Elements of group II

II A II B

Be Beryllium Zn Zincum

Mg Magnesium Cd Cadmium

Ca Calcium Hg Hydrargyrum

Ba Barium

Sr Strontium

Ra

Alkaline earth

metals

Magnesium Mg

PLANTS: Mg2+ - central atom of green pigment CHLOROPHYLL

(photosynthesis)

in human body: ~ 20 g Mg > ½ in bones ( Ca-Mg phosphates ) intracellular cation

Mg2+ activates number of enzymes !!! ENZYMES using ATP"kinases"

glucose glucose–6–phosphate

(Enzymes of ATP-dependent reactions require Mg2+ as cofactor)

hexokinase

ATP ADP

other effects of Mg2+: anti-convulsive effect

(MgSO4 - prevention of eclamptic convulsions)

influence on neuromuscular excitability

can help to prevent kidney and gall stones

"duodenal reflex" - MgSO4 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 Mg2+ )

Magnesium mineral water (Karlovy Vary) purgative effect

Calcium Ca

CaO + H2O Ca(OH)2

"slaking"

slaked lime

"burning"CaCO3

limestone, chalk

quicklime

CaO + CO2

Ca(OH)2 + CO2 CaCO3 + H2O

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 Ca2+ 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

Ca5 (PO4)3 OH

Hormones regulating Ca metabolism

Parathormone - peptide hormone ( 84 amino acids )

- secreted by parathyreoid glands

- activation of bone mineral degradation

Ca2+ release from bones

- stimulation of Ca2+ readsorption in kidney- stimulation of calcitriol formation (kidneys)- stimulation of Ca-resorption protein formation (ileum)

Ca2+ 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 Ca2+ excretion in kidney

Salmon calcitonin is used for the treatment of OSTEOPOROSIS

Ca2+ in blood

Calcitriol = 1,25-dihydroxycholecalciferol

- active form of D–vitamin

- stimulation of Ca-resorption protein formation

absorption of calcium from the gastrointestinal tract

Ca2+ increase PTH release inhibition

Ca – FOOD (protein-bound)

ILEUM

Ca-resorption protein

PLASMA

Ca 2.5 mmol/l

Ca2+ 1.2 mmol/l

URINEBONES

PTH

PTH

PTH

calcitonin

calcitonin

calcitriol

calcitriol

milkexcrements

Very low concentration of Ca2+ in cytoplasma 10-6 mol/l

MUSCLE - Ca2+ is stored in sarcoplasmic reticulum (SR)

CALSEQUESTRIN = calcium-binding protein of the SR

40 Ca2+ binding sites

Ca2+ in cytoplasma can cause the specific action of the cell:

MUSCLES contraction

Ca2+ = important SECOND MESSENGER

"SIGNAL"

release of Ca2+

EFFECT

endoplasmic reticulum

Clotting of BLOOD

Ca2+ is required for the proper function of the coagulation CASCADE

Xa

Fibrinogen Fibrin

Prothrombin Thrombin

Extrinsic pathway

(Tissue factor pathway)

Intrinsic pathway

(Contact activation pathway)

Removing of Ca2+ = NO clotting !

Anticoagulants - bind Ca2+ ions( "in vitro" = outside the body)

Oxalate

EDTA = ethylenediamine tetraacetic acid

COO -

COO -

COO

COO + Ca2+ Ca

Citric acid

Gypsum, plaster of Paris

CaSO4 . 2 H2O

CaSO4 . 2 H2O

CaSO4 . 1/2 H2O

+ H2O

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 Ca2+ 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 metalwater-soluble compounds - strongly neurotoxic

[ Ba(NO3)2 BaCl2 ] - painful cramps, tremor

BaSO4 (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 H2O + CO2 H2CO3 H+ + HCO3-

alcohol dehydrogenase - oxidation of ethanol to acetaldehyde

CH3CH2OH CH3CHO

NAD+ NADH+H+

Insulin binds ZINC ! "Zn – insulin hexamers"

Metallothionein - protein synthesized in kidneys rich of -SH groups

- can bind metals ( Zn2+ Cd2+ .... )

- zinc transport, heavy metal detoxification (Hg2+) ?

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): Zn3(PO4)2 . 4 H2O "hopeit"

Cadmium Cdtoxic heavy metal

metallothionein – strongly binds Cd2+

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 ( Zn2+ 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

HgCl2 - "sublimate" - soluble in water = toxic

- corrosive ulceration of GI tract

- renal failure

Hg2Cl2 – "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(CH3)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 Hg2+

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 A III B

B Borum Sc

Al Aluminium Y

Ga La

In Ac

Tl

Ra

Boron B (Borum)

PLANTS – micromineral

Boric acid H3BO3 - a very weak acid

- disinfectant (used in dermatology and ophtalmology)

- also toxic properties !

NH3 + glutamate glutamine

glutamine synthetase

H3BO3 = inhibitortoxic to BRAIN

Sodium tetraborate Na2B4O10 = 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 Al3+ !

Elements of group IV

IV A IV B

C Carboneum Ti

Si Silicium Zr

Ge Hf

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, CO2

respiration CO2

Toxic: CO competes with O2 for hemoglobin

HCN reaction with cytochromes inactivation of cell respiration

Silicon Si (Silicium)

abundant element in lithosfere, but not useful in human body

SiO2 (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 SiO2 dust SILICOSIS - lung disease

occupational disease (miners, ceramics workers)

progressive, signs of it will appear years after exposure !

Silicic acids: general formula n SiO2 . m H2O

H4SiO4 orthosilicic acid

Silicates - salts of silicic acids SiO44-

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