Elements of group V

V A V B

N Nitrogenium V Vanadium

P Phosphorus Nb

As Arsenicum Ta

Sb Stibium

Bi Bismuthum

Nitrogen N (Nitrogenium)

N2 78% of the atmosphere - chemically rather inert

- principal bioelement: organic compounds ( "NH3 derivatives" )

AMINO ACIDS PROTEINS

many heterocyclic compounds

pyrimidine

purine

uracil, thymine, cytosine

adenine, guanine

NUCLEIC ACIDS

(DNA, RNA)

NH3 ammonia - sharp odour

NH4+ ammonium ion

N2O Nitrous oxide [ Dinitrogen oxide ]

= "laughing gas"

- surgery: inhalation insensibility to PAIN

= anaesthetic and analgetic effects (without muscle relaxation)

obstetrics - pain relief during childbirth

NO Nitric oxide [ Nitrogen monoxide ]NO2 Nitrogen dioxide - reddish-brown gas

toxic properties for animals

in the environment

-toxic gases

(Photochemical smog)

Biological functions of NO

= important gaseous signaling molecule !!!

EDRF = endothelium-derived relaxing factor = NO

NO synthesis

Endothelial cell

relaxation

Smooth muscle cellNO

diffusion

Nitroglycerin = glyceryl trinitrate - oily explosive liquid [ DYNAMITE ]

NO

Nitroglycerin vasodilator

- treatment of angina pectoris

(a lack of blood suply of heart muscle chest pain)

Biochemical formation of NO

Arginine (amino acid)

Citrulline

NOenzyme: NO synthase

Functions of NO: 1) dilation of blood vessels vasodilator ( = EDRF ) 2) neurotransmitter 3) in macrophages and neutrophils – immune response

(NO is toxic to bacteria) 4) role in penile erection

halflife: ~ 4 sec.

HNO2 Nitrous acid (INN: Acidum nitrosum) - weak acid, not stable

salts: nitrites NaNO2 Sodium nitrite (INN: Natrii nitris)

- toxic !

food additive: alters the color of preserved meat

prevents growth of Clostridium botulinum

(botulinum toxin botulism)

organic nitrites = esters of nitrous acid

HNO3 Nitric acid (INN: Acidum nitricum) - strong acid

- oxidazing agent !

salts: nitrates AgNO3 Silver nitrate (INN: Argenti nitras)

Amyl nitrite – treatment of angina pectoris

Toxicity of NO2- (NO3

-)

intestinal bacteria can reduce nitrates to nitrites: NO3- NO2

-

Limits for drinking water: NO3- 50 mg/l adults 15 mg/l infants

1) Methemoglobinemia "blue baby syndrom"

HEMOGLOBIN

FeII

METHEMOGLOBIN

FeIII

nitrites

unable to transfer O2

methemoglobin reductase

"protective enzyme" - insufficient in infants !

2) Nitrosamines

Nitrites can react with secondary amines Nitrosamines

CARCINOGENS !

Nitrites in food - meat and cheese products preserved with

nitrite pickling salt !!!

Phosphorus P

- principal bioelement

H3PO4 Phosphoric acid (INN: Acidum phosphoricum)

- in biochemistry: "phosphates" = esters of H3PO4

1) Bone and tooth mineral: hydroxyapatite Ca5(PO4)3OH

2) Anions in body fluids: H2PO4- / HPO4

2-

3) Nucleotides, DNA, RNA

4) Structural lipids (phospholipids) - membranes !

5) Metabolic intermediates (Glucose–6–phosphate, ...)

6) High energy compounds ATP

ATP = adenosine triphosphate

phosphoanhydride bonds

ester bond

ATP + H2O ADP + Pi + energy

ATP + H2O AMP + PPi + energy

pyrophosphate

E = - 30.5 kJ/mol

ATP = adenosine triphosphate

ATP is used to drive many energy consuming reactions !

ATP is used as "energy" for active transport ("pumps")

ATP is often used to "activate metabolites":

ATP ADP

hexokinase

glucose glucose-6-P

ATP is formed from ADP when "fuel molecules" are oxidized.

glucose CO2 + H2O up to 36-38 ATP / molecule of glucose

(majority of this ATP production: oxidative phosphorylation in mitochondria)

Organophosphate neurotoxins

Sarin

Parathion

Sarin, soman, tabun - "nerve gases"

- extremely toxic substances !!!

- chemical weapons of mass destruction

very potent insecticid

also highly toxic !

inhibition of the enzyme acetylcholinesterase !

neuronal synapse neurotransmitter receptor effect

vesicles with neurotransmitter

synaptic cleft receptor

Neurotransmitter must be removed from the synaptic cleft (after its job is done) !

1) REUPTAKE

2) Enzymatic breakdown into inactive fragments - ACETYLCHOLINE

(acetylcholinesterase)

1)

2)

Cholinergic synapses ( neurotransmitter = acetylcholine )

ACH receptor

vesicles with acetylcholine (ACH)

acetylcholine choline acetic acid

*

synaptic cleft

botulinum toxin (release of ACH is blocked)

ATROPINE(ACH receptor is blocked)

organophosphates(acetylcholinesterase is blocked)

*

* acetylcholinesterase

As Arsenicum - toxic in all forms

dentistry – root canal therapy (devitalisation of tooth) arsenic compounds

SALVARSAN - organic compound containing As

- drug that was used to treat syphilis !

- the first effective "chemotherapeutic agent"

before penicillin (1940s)

- severe side effects

Elements of group VI

VI A VI B

O Oxygenium Cr Chromium

S Sulfur Mo Molybdaenum

Se Selenium W Wolframium

Te Tellurium

Po

Chalcogens

Oxygen O (Oxygenium)

O2 21% of the atmosphere

- principal bioelement: H2O

many functional groups in biomolecules

- OH "hydroxyl group" alcohols, phenols

"carbonyl group" aldehydes, ketones

- COOH "carboxyl group" carboxylic acidsC O

electron acceptor in biologically important oxidations !

O2 + 4 e- 2 O2- 2 H2O+ 4 H+

Oxygen radicals - TEXTBOOK (Toxicity of oxygen)

very reactive can cause damage to most cell components !!!

O2 + e- O2- superoxide radical

O2H perhydroxyl radical(hydroperoxyl)

H2O2 + e- OH- + OH hydroxyl radical

ROS = reactive oxygen species "free radicals" + H2O2 , ....

+ H+

Sulphur S (Sulfur)

- principal bioelement

H2S Hydrogen sulphide - strong poison

- gas with odour of rotten eggs

- SH sulfhydryl groups in organic structures

(often: active groups of proteins – enzymes)

protein SH

SH

Toxic heavy metals ( Pb, Hg, As, ...) - block sulfhydryl groups !

H2SO3 Sulphurous acid (INN: Acidum sulfurosum) - weak acid

salts: sulphites ( ........ sulfis )

H2SO4 Sulphuric acid (INN: Acidum sulfuricum) - strong acid

salts: sulphates ( ........ sulfas )

H2S2O3 Thiosulphuric acid (INN: Acidum thiosulfuricum)

salts: thiosulphates

( ........ thiosulfas )

H2S Hydrogen sulphide (INN: Acidum hydrosulfuricum)

salts: sulphides ( ........ sulfuridum )

Amino acids containing sulphur

cysteine ( Cys )

methionine ( Met )

- essential amino acids

- in proteins

Redox reactions

R SH R S

R‘ SH R‘ S

- 2 H

+ 2 Hdisulfide bond - S – S -

disulfide bonds stabilize the folded form of a protein

S

S

S

S

S

S

intramolecular -S-S- bondintermolecular -S-S- bonds

R SH R S OH

O

O

"sulfates"oxidation

sulfate groups - modification of polysaccharides

(heparine, chondroitin sulfate, keratan sulfate, ...)

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

Vitamins containing S

lipoic acid

biotinvitamin B1 (thiamin)

important

COENZYMES

coenzyme A Acetyl-CoA

important molecule in metabolism

Coenzyme A - thiol

("high energy bond")

- acyl group carrier thiol + carboxylic acid thioester

pantothenic acid

Selenium Se

trace element

- in enzymes: glutathion peroxidase (destruction of peroxides)

- chemically related to sulphur analogous amino acids

selenocysteine

= "rare amino acid" in some proteins: thyroid hormone deiodinases

Elements of group VII

VII A VII B

F Fluorum Mn Manganum

Cl Chlorum Tc

Br Bromum Re

I Iodum

At

Halogens

Fluorine F (Fluorum)

trace element F2 yellowish very reactive gas

Ca5(PO4)3F fluorapatite - bones, teeth

compounds of fluorine ( NaF ) – toothpaste to prevent dental caries

excessive consumption of F- "fluorosis" - damage of dental enamel

(white spots, mottling of enamel)

Freons (chlorofluorocarbons) - destruction of O3 layer

Hydrofluorocarbon derivatives - inhalational general anaesthetics

halothane

(isofluran, sevofluran, ...)

Chlorine Cl (Chlorum)

Cl2 pale green poisonous gas, suffocating odour

World War I chemical weapon destruction of lungs !

(it was soon replaced by more deadly gases – phosgene, ...)

Cl2 + H2O HCl + HClO

HClO HCl + O

Chlorination of water - to KILL bacteria

COCl2

O

Cl C Cl

Cl- important anion in body fluids

the main EXTRAcellular anion (97 – 108 mmol/l)

Physiologic saline solution (= isotonic = same osmolality as blood plasma)

NaCl 0.9 %

Inorganic acids

HCl Hydrochloric acid Acidum hydrochloricum

HClO Hypochlorous acid Acidum hypochlorosum

HClO2 Chlorous acid Acidum chlorosum

HClO3 Chloric acid Acidum chloricum

HClO4 Hyperchloric acid Acidum hyperchloricum

HCl - stomach !

CHCl3 Chloroform - one of the first anesthetics (~ 1850)

- inhaled vapour insensibility "painless sugrery"

- hepatotoxic !

- 2 CHCl3 + O2 2 HCl + 2 COCl2

CCl4 Tetrachloromethane (Carbon tetrachloride)

- solvent

- hepatotoxic ! ( = liver damage )

CH3CH2Cl Ethyl chloride

- boiling point 13o C

- evaporation cooling down the skin pain relief

- local skin anesthesia (sport injuries , ...)

CH2 CHCl Vinyl chloride - is used to produce its polymer: PVC

phosgene !

(war gas)

DDT (dichloro-diphenyl-trichloroethane)

contact poison for INSECTS only:

lipids of insect cuticule penetration to nervous ganglia paralysis death

DDT was used with great effect to prevent insect-borne diseases !

(mosquitoes – MALARIA lice – spotted TYPHUS)

environmental impact ! - long half life = persistent pollutant

magnifying through the food chain accumulation in fatty tissue

(reproductive toxicity, carcinogen ?, ...)

1960s USA - DDT - major reason for the decline of the bald eagle

(impaired quality of eggshells)

best known banned pesticide (insecticide)

high solubility in lipids !

Polychlorinated biphenyls PCBs

biphenyl

good technical properties were used as: insulating materials

cooling fluids in transformers

additives in plastics

PROBLEM: very stable ! = persistent pollutants BANNED

contamination of soil plants animals cumulation in lipids, milk

(carcinogens ?)

DIOXIN

tetrachlorodibenzo-1,4-dioxin

TCDD

(the most toxic dioxin)

general poison LD50 = 10 - 100 g/kg ("lethal dose")

very stable, very resistant (up to 800o C) persistent pollutant

accumulation in fatty tissues - teratogens, mutagens, carcinogens

by-product of production of herbicides

Vietnam War - Agent Orange (herbicide contaminated by TCDD)

1976 Seveso (Italy) - industrial accident – uncontrolled reaction

explosion of chemical reactor cloud containing dioxin !

Iodine I (Iodum)

trace element

as element: purple – black solid sublimes into purple gas !

- solubility in water can be increased by addition of KI

Lugol‘s solution ( I2 KI water )

tincture of iodin = I2 in ethanol

starch + iodine complexes of deep blue color

starch = mixture of -amylose – linear polymer of glucose

amylopectin – branched polymer of glucose

- polysaccharide of PLANTS in FOOD

desinfectant

Thyroid hormones

T4 thyroxine

T3 triiodothyronine

smaller quantity, greater

activity !

deiodinases in tissues

Se (selenocysteine) !

Function: stimulation of metabolism (act to increase the metabolic rate)

essential to proper development (BRAIN !)

Disorders

Deficiency of thyroid hormones = hypothyroidism

metabolism low body temperature

intolerance to cold

weight gain

weakness, lethargy

- children: mental retardation, short stature [ CRETENISM ]

Excess of thyroid hormones = hyperthyroidism ( Grave‘s disease ) metabolism intolerance to heat

weight loss

increased heart rate

(tachycardia)

GOITER (Latin STRUMA) = enlarged thyroid gland

(function of the gland can be low, normal, high)

Iodine is necessary for the synthesis of the thyroid hormones !!!

THYREOGLOBULIN

hormone release into the blood

proteolysisTSH (Thyroid-stimulating hormone)

2 I- I2

iodination

thyroid peroxidase

FOOD BLOODTHYROID GLAND

very effective in uptake of I-

from blood !!!I-, IO3-, ...

Thyroid gland is composed of spherical "follicles"

thyreoglobulin

T4, T3 release into blood

I2

uptake of I-

I-

follicular cells

"Colloid" inside the follicles is

rich in protein

THYREOGLOBULIN

Iodine in food

seafood - rich of iodine !

inland areas (Czech republic !!!) iodine deficiency

"endemic goiter"

"endemic cretenism"

prevention: iodised SALT ( = table salt fortified with NaI, KI, or KIO3)

( 25 mg KI / 1 kg of salt )

Elements of group VIII

VIII A VIII B

He Fe Co Ni

Ne Ru Rh Pd

Ar Os Ir Pt

Kr

Xe

Rn

Ferrum

Cobaltum

Niccolum

Noble gases

Iron Fe (Ferrum)

important microelement

human body: 4–5 g Fe

a) functional form - heme iron proteins hemoglobin 70 %myoglobin 5

%

some enzymes

- non-heme iron proteins

b) tranport form (transferrin)

c) storage of iron (ferritin, hemosiderin) 20 %

Fe in food 10-30 mg/day absorption: only 7-10% ~ 1 mg/day

HEME iron proteins

Hemoglobin - O2 transport in blood

- in red blood cells

- tetramer = 4 subunits

(each subunit: one heme + one globin)

HbA ("adult") 22

HbF ("fetal") 22

Myoglobin - "O2 store" in muscle cell

Cytochromes - electron transport

- their function is based on: Fe2+ (reduced) Fe3+

(oxidized)

heme

Non-heme iron proteins FeII or FeIII bound to protein SH

iron–sulphur proteins (FeS proteins)

Transferrin - blood plasma protein ( 1 globulin )

- transport of Fe

- 1 molecule of transferrin can carry 2 iron ions in form of Fe3+

Ferritin - intracellular iron storage protein (liver, bone marrow)

- 1 ferritin complex can store about 4500 Fe3+

- ferritin without iron = apoferritin

Hemosiderin - "damaged (Fe-overloaded) ferritin" - Fe from it is less available

Overview of iron metabolism

liver

FERRITIN HEMOSIDERIN

blood plasma

TRANSFERRIN

bone marrow

FERRITIN

red blood cells

HEMOGLOBIN

spleen

FERRITIN

tissues

CYTOCHROMES

Fe-S proteins

muscles

MYOGLOBIN

BLEEDING (Fe losses)

FOOD

Iron metabolism = unique

- reutilization ! (closed system)

NO regulated excretion system for Fe !

Fe absorption must be "regulated"

Loss of Fe through loss of blood (females - mestrual bleeding)

Iron deficiency - microcytic anemia "iron deficiency anemia"

Iron overload - hemochromatosis = accumulation of iron in the body

(depositions as hemosiderin)

organ dysfunction (liver, heart, ...)

Iron absorption

FOOD Fe3+

STOMACH

HCl pH 1-2

ascorbic acid

gastroferrin - iron binding protein

Fe2+

reduction

INTESTINAL MUCOSA CELL

Fe3+

apoferritin ferritin (Fe3+)

BLOOD

transferrin (Fe3+)Fe2+

Cobalt Co (Cobaltum)

trace element

- central atom of vitamin B12 (cobalamin)

(daily intake ~ 1 g "the liver store": 3–5 years !)

Absorption of vit. B12

gastric parietal cells intrinsic factor

absorption in terminal ileum

B12

complex B12 – intrinsic factor

Vit. B12 deficiency

megaloblastic anemia

pernicious anemia – due to impaired absorption !