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Medical Chemistry (1 st year – GM) Lecture III MUDr. Vlastimil Kulda October 16 th , 2012. Elements of group V. adenine, guanine. Nitrogen N (Nitrogenium) N 2 78% of the atmosphere - chemically rather inert
Nitrogen N (Nitrogenium)
N2 78% of the atmosphere - chemically rather inert
AMINO ACIDS PROTEINS
many heterocyclic compounds
uracil, thymine, cytosine
NH3ammonia - sharp odour
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 ]
NO2Nitrogen dioxide - reddish-brown gas
Smooth muscle cell
Biological functions of NO
= important gaseous signaling molecule !!!
EDRF = endothelium-derived relaxing factor = NO
- treatment of angina pectoris
(a lack of blood suply of heart muscle chest pain)
Nitroglycerin = glyceryl trinitrate - oily explosive liquid [ DYNAMITE ]
enzyme: NO synthase
Biochemical formation of NO
halflife: ~ 4 sec.
Functions of NO: 1) dilation of blood vessels vasodilator ( = EDRF )
3) in macrophages and neutrophils – immune response
(NO is toxic to bacteria)
4) role in penile erection
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
HNO3Nitric 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"
unable to transfer O2
"protective enzyme" - insufficient in infants !
Nitrites can react with secondary amines Nitrosamines
Nitrites in food - meat and cheese products preserved with
nitrite pickling salt !!!
H3PO4 Phosphoric acid (INN: Acidum phosphoricum)
- in biochemistry: "phosphates" = esters of H3PO4
ATP + H2O AMP + PPi + energy
ATP = adenosine triphosphate
DE = - 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 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)
- extremely toxic substances !!!
- chemical weapons of mass destruction
very potent insecticid
also highly toxic !
inhibition of the enzyme acetylcholinesterase !
neuronal synapse neurotransmitter receptor effect
Neurotransmitter must be removed from the synaptic cleft(after its job is done) !
2) Enzymatic breakdown into inactive fragments - ACETYLCHOLINE
(release of ACH is blocked)
vesicles with acetylcholine (ACH)
Cholinergic synapses ( neurotransmitter = acetylcholine )
(acetylcholinesterase is blocked)
(ACH receptor is blocked)
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
O2 + 4 e- 2 O2- 2 H2O
+ 4 H+
Oxygen O (Oxygenium)
O2 21% of the atmosphere
many functional groups in biomolecules
- OH "hydroxyl group" alcohols, phenols
"carbonyl group" aldehydes, ketones
- COOH "carboxyl group" carboxylic acids
very reactive can cause damage to most cell components !!!
O2 + e- O2- superoxide radical
O2H perhydroxyl radical
H2O2 + e- OH- + OH hydroxyl radical
ROS = reactive oxygen species "free radicals" + H2O2 , ....
Sulphur S (Sulfur)
H2S Hydrogen sulphide - strong poison
- gas with odour of rotten eggs
- SH sulfhydryl groups in organic structures
(often: active groups of proteins – enzymes)
Toxic heavy metals ( Pb, Hg, As, ...) - block sulfhydryl groups !
salts: sulphites ( ........ sulfis )
H2SO4Sulphuric acid (INN: Acidum sulfuricum) - strong acid
salts: sulphates ( ........ sulfas )
H2S2O3 Thiosulphuric acid (INN: Acidum thiosulfuricum)
( ........ thiosulfas )
H2S Hydrogen sulphide (INN: Acidum hydrosulfuricum)
salts: sulphides ( ........ sulfuridum )
Amino acids containing sulphur
methionine ( Met )
- essential amino acids
- in proteins
R SH R S
R‘ SH R‘ S
- 2 H
+ 2 H
R S OH
disulfide bond - S – S -
disulfide bonds stabilize the folded form of a protein
intermolecular -S-S- bonds
intramolecular -S-S- bond
(heparine, chondroitin sulfate, keratan sulfate, ...)
Vitamins containing S
vitamin B1 (thiamin)
Coenzyme A - thiol
- acyl group carrier
thiol + carboxylic acid thioester
("high energy bond")
important molecule in metabolism
- in enzymes: glutathion peroxidase(destruction of peroxides)
- chemically related to sulphur analogous amino acids
= "rare amino acid" in some proteins: thyroid hormone deiodinases
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
(isofluran, sevofluran, ...)
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
Cl C Cl
the main EXTRAcellular anion (97 – 108 mmol/l)
Physiologic saline solution(= isotonic = same osmolality as blood plasma)
NaCl 0.9 %
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)
- 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
high solubility in lipids !
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)
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
(the most toxic dioxin)
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 a-amylose – linear polymer of glucose
amylopectin – branched polymer of glucose
- polysaccharide of PLANTS in FOOD
deiodinases in tissues
Se (selenocysteine) !
smaller quantity, greater activity!
Function: stimulation of metabolism (act to increase the metabolic rate)
essential to proper development (BRAIN !)
metabolism low body temperature
intolerance to cold
- children: mental retardation, short stature [ CRETENISM ]
Excess of thyroid hormones = hyperthyroidism ( Grave‘s disease )
metabolism intolerance to heat
increased heart rate
GOITER (Latin STRUMA) = enlarged thyroid gland
(function of the gland can be low, normal, high)
very effective in uptake of I- from blood !!!
I-, IO3-, ...
Iodine is necessary for the synthesis of the thyroid hormones !!!
TSH (Thyroid-stimulating hormone)
hormone release into the blood
uptake of I-
Thyroid gland is composed of spherical "follicles"
T4, T3 release into blood
"Colloid" inside the follicles is
rich in protein
seafood - rich of iodine !
inland areas (Czech republic !!!) iodine deficiency
prevention: iodised SALT ( = table salt fortified with NaI, KI, or KIO3)
( 25 mg KI / 1 kg of salt )
Elements of group VIII
human body: 4–5 g Fe
a) functional form - heme iron proteins hemoglobin 70 % myoglobin 5 %
- 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
Hemoglobin -O2 transport in blood
- in red blood cells
- tetramer = 4 subunits
(each subunit: one heme + one globin)
HbA ("adult") a2b2
HbF ("fetal") a2g2
Myoglobin- "O2 store" in muscle cell
Cytochromes- electron transport
- their function is based on: Fe2+ (reduced) Fe3+ (oxidized)
iron–sulphur proteins (FeS proteins)
Transferrin- blood plasma protein ( b1 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
red blood cells
BLEEDING (Fe losses)
Overview of iron metabolism
- 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, ...)
HCl pH 1-2
gastroferrin - iron binding protein
INTESTINAL MUCOSA CELL
(daily intake ~ 1 mg "the liver store": 3–5 years !)
Vit. B12 deficiency
pernicious anemia– due to impaired absorption !
Absorption of vit. B12
gastric parietal cells
complex B12– intrinsic factor
absorption in terminal ileum