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