Water
non-bonding electron pairs
O
H2O
H
105o
H
bent molecule
d-
polar character
O
H
d+
-
H
+
d+
electrical dipole
Hydrogen bonding
-
attractions between water molecules
+
+

+
-
+
-
+
0 oC
3.6
/ H2O
HIGH melting point
boiling point
specific heat
heat of vaporization
surface tension
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)
WATER - very good solvent !
Attraction between
water dipoles and ions
"hydrated ions"
Dispersing "amphipathic" molecules
"micelles"
"Amphipathic" molecules – contain both highly hydrophobic
and highly polar groups
palmitic acid
non-polar chain = hydrophobic
polar group = hydrophilic
(water-fearing)
(water-loving)
Phospholipids
phosphatidylcholine
(lecithin)
polar groups
Biological membranes
- separate the cells
separate the spaces (compartments) of the cell
cell membrane
mitochondria
nucleus
lysosome
endoplasmic reticulum
Phospholipid BILAYER
hydrophilic
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
Phosphates
Proteins
K+
Na+ Mg2+
Na+
Cl-
Na+
K+
Ca2+
HCO3-
Mg2+
Phosphates
K+
Na+/K+ pump
( = Na+/K+ -ATPase )
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:
Excretion:
Saliva
Stomach
Bile
Pancreas
Small intestine
1 500 ml / day
2 500
500
700
3 000
Urine 60 %
Skin
20 % (perspiration)
Lungs 15 %
Faeces 5 %
8 200 ml /day
Human blood plasma
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
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
SELECTIVE permeability
(membrane = barrier)
- receptors
- transport systems
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
"channels"
2) Active transport
"pumps"
- does not involve energy
- diffusion from high to low concentration
- uses energy (ATP)
- can transport against the concentration gradient
- one direction, high specificity
ATP
3) Secondary active transport - no direct need of energy
- gradient created by active transport is used !
Passive transport
concentration and
electrochemical
GRADIENT
1
2
3
1) Simple diffusion
toward equilibrium
small molecule, NO charge, solubility in lipids !
O2
CO2
2) Ion channels - pore-forming proteins
- can be "GATED"
"gate" is closed
3) Facilitated diffusion ("carrier proteins")
"gate" is open
- selective !
- large molecules, insoluble in lipids
Ion transport antibiotics
Gramicidin
- peptide: 15 amino acids
HELIX - hydrophilic groups inside
"wet channel"
- lipophilic groups outside
increase of the permeability of bacterial cell wall
inorganic ions can travel through
equilibration of concentrations = NO GRADIENT
"wide wet pore"
Valinomycin
hydrophillic groups INSIDE = "WET cave"
hydrophobic (lipophillic) groups OUTSIDE
( = soluble in lipids of membrane)
K+
highly selective carrier for
K+
K+
( Na+ with water coating is too big)
equilibration of K+ concentration = NO GRADIENT
K+
Valinomycin
hydrophillic groups
hydrophobic (lipophillic) groups
Active transport = "PUMPS"
Transport against
GRADIENT
ENERGY !
ATP
ADP + Pi
Na+/K+ ATPase
(sodium potassium pump)
ATP
INHIBITION:
cardiotonic steroids
2 K+
3 Na+
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
inhibitors of this pump:
-
outer side of the membrane
+
cardiotonic steroids = cardiac glykosides
(oubain, digoxin)
 treatment of heart failure, cardiac arrhytmia
Digitalis purpurea
(foxglove)
H+/K+ ATPase
stomach  gastric acid
CO2
* carboanhydrase
Zn2+
HCl
CO2 + H2O
*
H2CO
3
HCO3-
H+ Cl-
K+
ATP
HCO3- + H+
Clblood pH = 7.4
parietal cell
106 increase of H+ concentration !
lumen of the stomach
pH = 1 - 2
Secondary active transport
"COTRANSPORT"
Na+ dependent transport of glucose, aminoacids, Ca2+
"energy" = Na+ gradient generated by Na+/K+ ATPase
Na+
glucose
SYMPORT
ANTIPORT
Na+
Ca2+
Na+ - glucose symport
glucose
glucose
Na+
K+
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
Ca2+
Ca2+
Na+
K+
Ca2+ ATPase
Na+/Ca2+ exchanger
Na+
ATP
 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 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
receptor
vesicles with
neurotransmitter
synaptic cleft
Water transport across membranes
Water moves by "simple diffusion" through membranes
?
Additional mechanism for water transport:
AQUAPORINS
"water channels"
Water transport - due to osmotic differences (osmotic gradient)
OSMOSIS
high osmolality
H2O
low osmolality
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
4)
Microelements (trace elements)
Ca
PO43-
Fe, Cu, Co, Zn, I, F, Se, ...
--------------------------------------------------------
5)
Contamination (intoxication):
Hg, Al, ...
Elements of group I
IA
Alkali
metals
IB
H
Hydrogenium
Cu
Cuprum
Li
Lithium
Ag
Argentum
Na
Natrium
Au
Aurum
K
Kalium
Rb
Cs
Fr
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
acidic solutions
7
neutral
alkaline (basic) sol. 14
water is weakly ionized:
H+ + OH-
H2O
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
dibasic acid: H2SO4
Weak acids – do not disociate completely:
Strong bases: NaOH, KOH, Ca(OH)2
Weak base: NH4OH
CH3COOH
H+ + Cl2 H+ + SO42H+ + CH3COO-
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
compounds:
LiCl
Li2CO3
Li
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
OH
N
N
HO
OH
N
NH
- poorly soluble in water
- lithium urate – more soluble !
Sodium
Na+
Na
(Natrium)
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
Elimination:
urine (95 %)
sweat (perspiration)
stool
food (common salt)
Kidney
Glomerular
filtration
BLOOD
Glomerular filtrate (180 l H2O / day)
[ 1.5 kg NaCl ]
Tubular
resorption
dependent on hormones
(aldosteron, ADH)
URINE
2 l H2O
5 – 15g NaCl
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+
K
the main INTRAcellular cation
(Kalium)
(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
Na+/K+ ATPase
EXTRAcellular fluid
cell membrane
INTRAcellular fluid
3Na+
2K+
Ion channels
Na+
ATP !
2K+
K+
rising phase = depolarisation
ACTION POTENTIAL
falling phase = repolarisation
resting potential
In cells K+ is bound to GLYCOGEN !
Diabetic coma
(
glucose in blood )
insulin
Glycogen synthesis
Binding of K+ in cells
Plasma K+ depletion
HEART failure !!!
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. )
- a2 globulin synthesized in the liver
- enzymatic activity: Fe2+  Fe3+
WILSON‘s DISEASE
(hepatolenticular degeneration)
- accumulation of copper in tissues
- 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
precious metal
Ag
( + H 2S
(Argentum)
 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
precious metal
Au
(Aurum)
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 A
Alkaline
earth
metals
II B
Be
Beryllium
Zn
Zincum
Mg
Magnesium
Cd
Cadmium
Ca
Calcium
Hg
Hydrargyrum
Ba
Barium
Sr
Strontium
Ra
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"
hexokinase
glucose
glucose–6–phosphate
ATP
ADP
(Enzymes of ATP-dependent reactions require Mg2+ as cofactor)
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
CaCO3
"burning"
limestone,
chalk
CaO + H2O
Ca
CaO + CO2
quicklime
"slaking"
Ca(OH)2
slaked lime
Hardening of mortar:
Ca(OH)2 + CO2
CaCO3 + H2O
Calcium
Ca
in human body ~ 1 kg (99% in bones, teeth)
dietary intake: 800 - 1200 mg / day
human blood plasma: "total Ca"
(extracellular !)
ionized Ca2+
2.5 mmol/l
1.2 mmol/l
resorption: ileum – specific protein carrier
~ 200 mg / day
excretion: urine
liver
bile
feces
Mineral constituents of bones and teeth
Hydroxyapatite
Ca5 (PO4)3 OH
Ffluoroapatite
enamel
dentin
cementum
pulp
Enamel: - hardest substance of the body
water
1-3 %
organic comp.
1%
mineral
> 95 %
(bones ~ 60 %)
Hormones regulating Ca metabolism
Parathormone - peptide hormone ( 84 amino acids )
- secreted by parathyreoid glands
PTH
- 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
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
Ca2+
in blood
Salmon calcitonin is used for the treatment of OSTEOPOROSIS
Calcitriol
= 1,25-dihydroxycholecalciferol
- active form of D–vitamin
- stimulation of Ca-resorption protein formation

absorption of calcium from the gastrointestinal tract
PTH
Ca – FOOD (protein-bound)
ILEUM
Ca-resorption protein
calcitriol
calcitonin
PLASMA
BONES
PTH
PTH
URINE
Ca 2.5 mmol/l
Ca2+ 1.2 mmol/l
calcitonin
calcitriol
milk
excrements
Ca2+ increase
PTH release inhibition
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
endoplasmic reticulum
"SIGNAL"
release of Ca2+
EFFECT
Clotting of BLOOD
Intrinsic pathway
Extrinsic pathway
(Contact activation pathway)
(Tissue factor pathway)
Xa
Prothrombin
Thrombin
Fibrinogen
Fibrin
Ca2+ is required for the proper function of the coagulation CASCADE
Removing of Ca2+ = NO clotting !
Anticoagulants - bind Ca2+ ions
( "in vitro" = outside the body)
Oxalate
COO COO -
Citric acid
+
Ca2+
COO
Ca
COO
EDTA = ethylenediamine tetraacetic acid
Gypsum, plaster of Paris
CaSO4 . 2 H2O
heating
CaSO4 . 1/2 H2O
+ H 2O
hardening
CaSO4 . 2 H2O
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
90
Sr
bone marrow irradiation 
LEUKEMIA
half life 28 years
(important isotope regarding health impacts after the Chernobyl disaster)
radioisotope
89
Sr
half life 50 days
- treatment of bone cancer
Barium Ba
toxic heavy metal
water-soluble compounds
[ Ba(NO3)2 BaCl2 ]
- strongly neurotoxic
- 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
microelement
Zn
(Zincum)
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
NAD+
CH3CH2OH
NADH+H+
CH3CHO
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 Cd
toxic 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 !
glutamine synthetase
glutamine
NH3 + glutamate
H3BO3 = inhibitor
toxic 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
HCN
 competes with O2 for hemoglobin
 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