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Biogenic elements
Classification according to their abundance in the organism:
Biogenic elements - necessary for the maintenance of life
processes (play an important biological role)
Macroelements (11 elements in total, form up to 99 % of any organism):
a) a group of stable primary elements, 2-65 % of total
organism weight (C, H, O, N)
b) a group of stable secondary elements, 0.05-2%
of total organism weight (Na, K, Ca, Mg, P, S, Cl)
Microelements (less than 0.05%):
a) a group of metals (Fe, Cu, Zn, Mn, Co, V, Mo, W)
b) a group of semi- and nonmetals ( Se, B, Si, F, I)
Water
substantial component of living organisms
newborn infant 80-70%, adult 60%, senior 50%
intake and elimination in equilibrium ≈ 2700 ml
intake: beverages, food, metabolism
elimination: urine, exhalation of vapour by lungs, sweat, feces
Hydrogen bonding between water molecules
Biological functions of water
• universal solvent and transport medium of inorganic
and organic compounds
• structural component of biological macromolekules
• activator of certain chemical reactions
• takes part in organism thermoregulation (high specific
heat capacity and heat of vaporization)
• substrate or product of some enzymatic reactions
Coordinate bond „Bond – Coordinate Bond“
Coordination compound – compound that contains a coordination entity:
[Co(NH3)6]Cl3hexaamminecobalt(III) chloride
- bond formed upon interaction between molecular species, one of which serves as a donor (ligand) and the other as an acceptor (central atom) of the electron pair to be shared in the complex formed
Coordination entity (or complex) – an ion or neutral
molecule composed of a central atom and ligands:
[Co(NH3)6]3+
Multidentate ligands - chelating ligands – contain more than 1 donor atom (form more than one bond with the central atom)
Coordination number = 6!
Chelates – complexes with multidentate ligands, ring structures, more stable
Co
NH2
NH2
NH2H2N
H2N NH2
H2N - CH2 - CH2 - NH2 = ethylenediamine [Co(en)3]3+
Coordination number – the number of σ-bonds betweenligands and the central atom, e.g. for [Co(NH3)6]3+ = 6Monodentate ligands – contain 1 donor atom (NH3 , H2O)
a) tetrapyrrolespartially unsaturated tetradentate macrocyclic ligands
porphin chlorin corrin
Biologically important ligands for metal ions
b) proteins - S, N, O donor atoms in the side chainsof aminoacids
c) nucleotides, DNA, RNAcoordination by nucleobases or by phosphate groups (N and O donor atoms)
CH2 CHHS
NH2
COOH CH2 CH2SH3C COOH
NH2
CH
C CH2
O
HOCH2 CH
NH2
COOHC CH2
O
HOCOOH
NH2
CH
N
NH
CH2 COOH
NH2
CH CH2 CH2CH2NHCH2N
NH
COOH
NH2
CH
histidín
metionín
arginín
cysteín
kyselina asparágová kyselina glutámováglutamic acidaspartic acid
histidine arginine
methioninecysteine
Sodium, potassium
Na+ - extracellular cationK+ - intracellular cationelectrolytes - charge cariers
Functions- transmission of the nerve impulses
- regulation of the osmotic pressure
- regulation of the enzyme activity
- transport processes
Na+ - necessary for regulation of body fluids
K+ - important for heart function
hyper- or hypokalemia abnormal heart rhythm
Magnesium
Mg2+ - intracellular cation
Functions
- regulation of the enzyme activity (important in the ATP
metabolism)
(DNA, RNA synthesis, protein synthesis, glycolysis)
- part of endoskeleton (in bones and teeth together
with Ca2+)
- transmission of the nerve impulses, muscle
contraction
- photosynthesis ( chlorophyll in plants)
Calcium
- the most abundant cation in the body
Ca2+ - 99 % in bones and teeth
≈ 1% in intra– and mainly extracellular space
in bones and teeth
hydroxyapatite Ca10(PO4)6(OH)2, (carbonate apatite, fluorapatite), Ca3(PO4)2,
together with Mg2+, Zn2+ and trace amounts Na+, Cu2+,
Functions
• it affects neuromuscular excitability (together with the ions K+, Na+, Mg2+) and it takes part in muscle contraction
• it takes part in regulation of glycogenolysis in liver and in regulation of gluconeogenesis in kidneys and liver
• it decreases cell membrane and capillary wall permeability, what results in its anti-inflammatory,anti- exudative and antiallergic effects
• it is necessary for blood coagulation
• it influences secretion of insulin into the circulation and secretion of digestion enzymes into smal intestine
IronFe(II), Fe(III)healthy adults 4 - 5 gthe daily absorption rate of iron supplied by foodamounts to 1-2 mg
≈ 65 % hemoglobin Fe(II) O2 transport
4 % myoglobin Fe(II) O2 storage in muscle
30% ferritin Fe(III) iron storage
0.2 % transferrin Fe(III) iron transport
the remaining iron – cytochromes, cytochrome c oxidase
(see Copper), catalase, aconitase, e.t.c.
Iron deficiency - sideropenia
main causes of iron deficiency :
• the poor availability of iron in the diet
• malabsorption
• chronic blood loss
• severe malnutrition
iron deficiency anemia
symptoms of iron deficiency:
pale skin , fatigue, headache, impaired physical capacity,
increased susceptibility to infections, retardation of growth
and cognitive performance (in infants and children)
treatment of iron deficiency:
• iron supplementation (preferably by oral route)
• blood transfusion
Iron overload
causes:
• excessive blood transfusions, hemolytic anemia -
hemosiderosis
• hereditary hemochromatosis – genetic disorder
causes tissue damage (mainly liver, heart and pancreas)
treatment of iron overload:
• phlebotomy (periodic blood removal)
• iron chelation therapy (desferrioxamine -Desferal)
Toxic effect of iron- transition metal
Fenton reaction:
Fe2+ + H2O2.OH + OH- + Fe3+
hydroxyl radical – damage to DNA, proteins, lipids
Free radicals (oxidants)
- atoms, molecules or their fragments with one or more
unpaired electrons capable for a short time of independent
existence
Reactive oxygen species (ROS):
free radicals (. OH, O2. −) and nonradical molecules such as
H2O2 , HClO, singlet oxygen
Hemoglobin
- in erythrocytestetramer – 4x globin + 4x hem hem = Fe(II) + protoporphyrin IX = chelate
Functions
- transport of O2 from lungs to tissues – oxyhemoglobin
-transport of CO2 from tissues to lungs –
carbaminohemoglobin
- contributes to the buffering capacity of blood
deoxyhemoglobin (without O2) binds H+/oxyhemoglobin releases H+
in tissues: O2 is released and deoxyhemoglobin binds H+ (one H+ for every two O2 molecules )in lungs: the reverse process
Carboxyhemoglobin – after CO poisoning
(CO has 200x higher affinity to Hb than O2)
• decreased oxygen-carrying capacity of Hb• decreased delivery of oxygen to cells
Notice
O2 and CO: bind to Fe(II) in heme
CO2 binds to globin (free -NH2 groups in side chains of amino
acids, e.g. lysin)
methemoglobin – Fe(II) Fe(III)
- biological inactive
Myoglobin
- hemoprotein in heart and skeletal muscle
- monomer (single polypeptide chain that is structurally
similar to the individual subunit polypeptide chains of
the hemoglobin molecule)
Functions
- reservoir for oxygen
- oxygen carrier (increases the rate of transport of
oxygen within the muscle cells)
Catalase
tetramer - 4x polypeptide chain + 4x hem
2H2O2 2H2O + O2
hydrogen peroxide – oxidant (e.g. oxidation of SH- group of cystein), substrate for free radical generation (.OH)
catalase is high-molecular weight antioxidant
Antioxidants – compounds which at low concentration prevent oxidative damage to molecules by oxidants.
Copper
Cu(II), Cu(I)
healthy adults 100 -150 mgpredominantly in: liver, muscles, bones and braindaily requirement ≈ 1mg
Copper deficiency
a) e.g. malabsorption
anemia (Cu influences Fe metabolizm )
b) Menkes syndrome
- hereditary dysfunction of copper transport
- affected the structure of bone, skin, hair, and blood vessels and nerve function
Copper overload
Wilson disease
- hereditary dysfunction of Cu transport and incorporation into ceruloplasmin - accumulation of Cu in liver and brain and cornea (dementia, liver failure)
www.wilsons.dk
corneal Kayser-Fleischer ring
treatment of copper overload : D-penicillamine
CH3
CH3 C CH COOH
S H N H2
donor atomshydrofilic group
Ceruloplasmin
- Cu transport
- Fe mobilisation and oxidation - ferrooxidase activity
- antioxidative effect:
1. oxidation of Fe2+ to Fe3+
preventing .OH formation (the role of Fe2+ in Fenton reaction!)
2. direct reaction with superoxide anion radical , O2−
Fenton reaction generaly
M(n-1)+ + H2O2.OH + OH- + Mn+
.
Superoxide anion radical (superoxid) produces hydroxylradical in Haber-Weiss reaction:
O2- + H2O2 O2 + OH- + .OH
Mn+ /M(n-1)+.
Cu/Zn Superoxidedismutase (Cu/Zn-SOD)
dimer (each subunit contain Cu(II) and Zn(II))
antioxidative activity – superoxide dismutation:
2O2.- + 2H+ O2 + H2O2
1. step: Cu2+ + O2.- Cu+ + O2
2. step: Cu+ + O2.- Cu2+ + H2O2
2H+
SOD
mitochondria
terminal oxidase of respiratory chain
O2 + 4H+ + 4e- 2H2OEnzyme
Cytochrome c oxidase
Zinc
Zn(II) – in contrast to Cu and Fe is not redox active
healthy adults 2-3 gdaily requirement 3-25 mg
Functions
a) catalytic role (conversion or degradation of proteins,
nucleic acids, lipids, porphyrin precursors)
b) structural role – stabilization of tertiary structure of
proteins (Cu/Zn-SOD)
• more than 200 metalloproteins contain zinc
Zinc deficiency
• disturbance of growth
• break-down of the immune system
• enhanced disposition for inflammations
• reduced sense of taste
Carbonic Anhydrase (carboanhydrase)
- very effective hydrolytic enzyme
H2O + CO2 HCO3- + H+
- pH control (bicarbonate buffer system)
Alcohol Dehydrogenase
- oxidation of primary and secondary alcohols to
aldehydes and ketones (cooperation with NAD+/NADH)
CH3 CH2 OH + NAD+ CH3 CHO + NADH +H+
CH3 OH + NAD+ H CHO + NADH +H+
ADH
ADH
methanol formaldehyde
ethanol acetaldehyde
CobaltCo(II), Co(III)
healthy adults 1 mg
85% in B12 (cobalamin) – bound to corrin
Function (B12 ):
• DNA and red blood cells synthesis (together with folic acid)
• maintenance of myelin sheath
deficiency – impairment of DNA synthesis, pernicious anemia, neurological dysfunctions
AxonMyelinsheath
Manganese(II), (III), (IV)deficiency – rare
Functions
• activator of many enzymes (hydrolases, transferases,
dekarboxylases)
• Mn-SOD in mitochondria- Mn(III)SOD
2O2.- + 2H+ O2 + H2O2
Toxic elements
Toxic elements
Effe
ct
+
-
Concentration
essential (Fe, Cu, Zn)
toxic (Pb, Cd, Hg)
positive
negative
Paracelsus (Philippus Aureolus Theophrastus Bombastus von Hohenheim)
"The right dose differentiates a poison and a remedy."
Toxic elements
Pb, Hg, Cd, Be, As, Tl, Ba
Toxic effect depends on:
• the dose
• physicochemical properties (redox state, solubility –
Ba(NO3)2 vs. BaSO4 , form)
• duration and route of exposure (inhalation, digestion
skin)
• organism (age, gender)
BaSO4
Metal toxicity is based on:
- substitution of essential for toxic metal ion
e.g. Zn2+ Cd2+, Pb2+, Hg2+
affects enzyme activity
- binding to the functional group of aminoacids in the side
chains of proteins (e.g. -SH) - affects enzyme activity
- binding to the negatively charged sites of the lipid
membrane - affects membrane transport
- binding to DNA – changes in genetic information
- oxidative damage – formation of reactive species (ROS,
RNS) oxidative damage to lipids, proteins and DNA
Mercurybinding to –SH groups of enzymes and membrane
proteins, Hg2+ Zn2+
liquid mercury - poorly absorbed from GIT (liquid state at room temperature, melting point -38 0C)
Toxic forms of Hg:
• mercury vapour
• soluble inorganic compounds (e.g. HgCl2 )
• organometallic compounds, e.g. methylmercury - CH3Hg+
Effects:
• nervous system – accumulation in the brain,
tremor, incoordination, loss of memory,
• renal, GIT, cardiovascular systems – kidney damage
abdominal crumps and pain, abnormal heart rhythm
and blood pressure
• accumulation in placenta – effect on fetal brain
development
- binding to –SH groups of enzymes
- Pb2+ Zn2+ , Ca2+
Effects:
• inhibition of hem synthesis anemia
• affects the biosynthesis of bones ( Pb2+ Ca2+ )
• nervous system - encephalopathy, depression,
muscular tremor
• renal and GIT - lead nephropathy,loss of apetite,
abdominal cramp and pain
• reproduction - spontaneous abortion, effect on
fetal brain development
Lead
Arsenic (metalloid)
Effects:
- binding to –SH groups of enzymes
- affects the generation of ATP - competition with phosphate
- carcinogenic effects – skin, lung, liver cancer
• cardiovascular, dermal, GIT, hepatic effects
AsO43-
Pi
Cadmium
highly toxic, lethal dose 350 mg
Cd2+ Zn2+ , Ca2+
binding to –SH groups of enzymes
• kidney damage• effects on bone – osteoporosis• carcinogen
Treatment of metal poisoning
1. Prevention of further absorption (e.g. by emptyingthe stomach)
2. Elimination of absorbed poison
• inactivation of absorbed poison – chelation therapy
• hemodialysis
3. Modification of response (reduction of symptoms)
Chelation therapy
- in the treatment of metal poisoning or metal-storage
diseases (Wilson disease)
Chelating agents (multidentate ligands):
• high affinity to toxic metal
• permeation to tissues where metal is deposited
• minimal interaction with biomolecules in organism
• minimal metabolism
• minimal toxicity of formed complex
• fast elimination from organism
Ligands used in chelation therapy:
D-penicillamine – Pb, Hg, Au, Zn, Cu (Wilson dis.)
Na2Ca EDTA – Pb
Dimercaptopropanol (DIMERKAPROL) – As, Hg (inorg.),
Sb, Cu, Zn
CH2 SH
CH SH
CH2 OH
Desferrioxamine (DESFERAL) – Fe, Al
NCH2CH2N
-OOCH2C
-OOCH2C
CH2COO-
CH2COO-
2Na+, Ca2+
desferrioxamine (DESFERAL, i.v.) – Fe, Al