Bulk and trace elements
-
Upload
truongkhue -
Category
Documents
-
view
231 -
download
5
Transcript of Bulk and trace elements
![Page 1: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/1.jpg)
Bulk and trace elements – bulk elements: C, H, O, N, S, P– maintaining the osmotic pressure body fluids
Na, K, Ca, Mg, Cl
– essential trace elements:F, I, Se, Si, Sn (main group elements)Fe, Zn, Cu, Mn, Mo, Co, V, Ni (transition metals)
– potential trace elements: B, Ti, As, Pb, Cd, W, ....– toxic elements
![Page 2: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/2.jpg)
Average abundance of trace elements(70 kg individual)
0.15100S1.0680P2.61815N9.76780H18.012590C65.145550OOrganic elements%weight (g)element
![Page 3: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/3.jpg)
0.000014 mgMo0.0000312-20 mgMn0.0001480-120 mgCu0.0042-4Zn
0.0074.2-4.6FeTrace elements(<100 mg/body kg)
0.0642Mg0.1070Na0.16115Cl0.36250K2.421700CaBulk elements
Average amount of trace elements (70 kg individual)
![Page 4: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/4.jpg)
Trace elements
1. The abundance of elements in different living organisms is in a given concentration range
2. The decreasing of abundance of elements causes physiological changes (diseases)
3. Administration of missing trace elements improve the physiological conditionThey take part in the metabolism.
4. The elements have defined biochemical functions
![Page 5: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/5.jpg)
Trace elements
µg/day 10 50 Se 200 103 104
mg/day 0,5 2 F 10 20 100
survival deficiency optimal toxicity lethalit
therapeutic width
![Page 6: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/6.jpg)
Roles of trace elements
1. Transport of biological small moleculespl. O2-transport: hemoglobin (Fe), hemocianin (Cu)
O2-storage: mioglobin (Fe)
2. Activation of molecules: metalloenzymes, enzymes activated by metal ionsa) catalysing of redox processes (Fe, Cu, Mn, Co, Mo, Ni)
biological oxidation, reduction of substrateb) catalysing of acid-base processes (Zn)
![Page 7: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/7.jpg)
3. Secunder conformation of macromolecules– determination of conformation of enzymes– determination of conformation of proteins, nucleic acids
4. Metabolism of microelements– uptaking, transport, storage of trace elements
Roles of trace elements
![Page 8: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/8.jpg)
Experimental methods for study of biological systems
− UV-visible (UV) spectroscopy (exited electron →groundstate)− electronspin resonance spectroscopy (ESR) (interaction between unpaired electron and magnetic field)− nuclear magnetic resonance spectroscopy (NMR) − X-ray diffraction (study of solid crystals)− Mössbauer spectroscopy (study of iron-, tin-complexes)− molecule modelling (computational modelling)
![Page 9: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/9.jpg)
Abundance of trace elements in a caveman andtoday (ppm)
1701,70,01Pb> 2000,19<0,001Hg7000,70,001Cd1,00,40,4Ti2,30,90,4Al2,30,70,3B1,00,030,03Co1,00,10,1Mo1,21,21,0Cu1,03333Zn1,06060Fe
ratiotodaycavemanelement
![Page 10: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/10.jpg)
Composition of earth crust and see water (ppm)
5⋅10–70,00355Cu∼10–8∼10–71-100Ln0,010,011,5Mo∼10–60,0005100Cr∼10–70,0014400Ti∼10–53,0277000Si∼10–70,0181300Al14619000130Cl0,371005028300Na
see/earthsee waterearth crustelement
![Page 11: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/11.jpg)
- circumstances of life origin- chemical factors(complex formation ability, solubility, reversibility of bound, hard-soft acid-base properties)
The origin of life
Chemical evolution: formation of simple and more complicate organic molecules from elementsPrebiological evolution: formation of living cells from group of complicate organic compoundsBiological evolution: the development of living world
![Page 12: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/12.jpg)
Coordination chemistry of metal ions
Complex formation proecesses:M(H2O)n + L ML(H2O)n-1 + H2O
MLn-1(H2O) + L MLn + H2O
M(H2O)n + nL MLn + nH2Oβn = K1·K2· ... ·Kn
]L][)OH(M[])OH(ML[K
n2
1n21
−=
]L)][OH(ML[]ML[K
21n
nn
−
=
nn2
nn ]L][)OH(M[
]ML[=β
![Page 13: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/13.jpg)
Complex formation processes
General equilibrium
pM + qA + rB + sH MpAqBrHs
M: metal ion (oxidation number: 1-3 (4)) or oxoanionA, B: ligands
![Page 14: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/14.jpg)
Types of coordination compoundsa/ parent complexes: complex formed with one ligand:
MA, MA2, MA3 .... MAN (N: coordination number)b/ mixed ligand complexes: complex formed with two or more ligands:
M + A + B MAB orMA2 + MB2 2MAB
c/ protonated complexes: the non-coordinated donor groups of ligands are protonated
M + HnA M(AH) + n–1 H+
Coordination chemistry of metal ions
![Page 15: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/15.jpg)
Types of coordination compoundsd/ deprotonated complexes: M + A M(AH–1) + H+
−deprotonation and coordination of ligands (e.g.: alcoholic group, amide group−deprotonation of coordinated water moleculeMA(H2O)n MA(H2O)n–1(OH) + H+
c/ polynuclear complexes: nM + mA MnAm
(A: bridge ligand or ligand containing more donor atoms)
Coordination chemistry of metal ions
![Page 16: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/16.jpg)
Reactions of metal complexes 1. Substitution of ligands
MA + B MB + Ain solution:
M(H2O)n + nA MAn + nH2Othermodinamic aspect: stable, instable complexes (lg β)kinetic aspect: labile (fast exchange), inert (slow exchange)Biological importance:
MXY + L MXL + Y(X - polifuntional macromolecule, Y – small molecule)e.g.: Zn-carboxypeptidase, Fe-mioglobin
Coordination chemistry of metal ions
![Page 17: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/17.jpg)
Reactions of metal complexes2. Redox reactions
ε(oxidated form) < εo < ε(reduced form)
Fe(III)/Fe(II) ε (V) Cu(II)/Cu(I) ε (V)εo H2O +0,77 H2O +0,17
OH– –0,56 glycine –0,16oxalate +0,02CN– +0,22 bipiridine +0,96 pyridine +0,27fenantroline +1,10 imidazole +0,35
CN– +1,10
Coordination chemistry of metal ions
![Page 18: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/18.jpg)
Factors influenced stability of complexes:• Type and charge of metal ion
- the complex of metal ion with +3 oxidation state is more stable- the stability of complexes of 3d elements with +2 oxidation state follow the Irving-Williams series
Mn(II) < Fe(II) < Co(II) < Ni(II) < Cu(II) > Zn(II)(related to the decrease in ionic radii)
Coordination chemistry of metal ions
![Page 19: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/19.jpg)
Factors influenced stability of complexes:• Type of metal ions and ligands
- hard metal ions (Lewis-acids) form stable complexes with ligands containing hard donor atoms (F, O) - soft metal ions (Lewis-acids) form stable complexes with ligands containing soft donor atoms (I, S)
• Type of ligands- formation of chelate rings (five- or six-membered ring) →enhance the stability of complexes: chelate effect
Coordination chemistry of metal ions
![Page 20: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/20.jpg)
Potential donor atoms in biological systems
• Hard-soft acid-base groups of metal ions and ligands
Oxigen containing ligands: H2O, CO3
2–, NO3–, PO4
3–, ROPO3
2–, (RO)2PO3–,
CH3COO–, OH–, RO–, R2O, crownethersNitrogen containing ligands:NH3, N2H4, RNH2,Cl–
H+, Na+, K+
Mg2+, Ca2+, Mn2+, VO2+
Al3+, Co3+, Cr3+, Ga3+, Fe3+, Tl3+, Ln3+, MoO3+
hard bases (ligands)hard acids (metal ions)
![Page 21: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/21.jpg)
,
Sulphur containing ligands:RSH, RS–, R2S, S2O3
2–
R3P, (RS)2PO2–,
(RO)2P(O)S–,RNC, CN–, CO, R–, H–, I–
Cu+, Au+, Tl+, Ag+, Hg22+
Pt2+, Pb2+, Hg2+, Cd2+, Pd2+, Pt4+,
soft bases (ligands)soft acids (metal ions)
Br–, SO32–,
Nitrogen containing ligands:NO2
–, N3–, N2,
Fe2+, Ni2+, Zn2+, Co2+, Cu2+,Pb2+, Sn2+, Ru2+, Au3+
intermediate bases(ligands)
intermediate acids (metal ions)
NH2
NNH
Potential donor atoms in biological systems
![Page 22: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/22.jpg)
The most important ligands in biological systems
• amino acid, peptide, protein• nucleic acid base, nucleoside, nucleotide• porfirins• polyphenols, carbohydrates, glycerides
Metal complexes of amino acids and peptides• -COO–-coordination: Na+, Ca2+, Al3+
• -NH2-coordination: Ag+, Hg2+
• (NH2,COO–) coordination: M2+ (M+, M3+) transition metal ions
![Page 23: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/23.jpg)
amino acid dipeptide
![Page 24: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/24.jpg)
coordination is influenced: • by R1-Rn sidechain• pl: Asp, Glu – carboxylate group,• His – imidazole ring, • Cys – SH-group
![Page 25: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/25.jpg)
Nukleinsavak és alkotórészeik
N
N N
N
O CH2 O P
O
-O
O P
O
O-
O P
O
O-
O-
NH2
HO OH
nukleobázis: N-donorok soft fémek
foszfát: O-donor hard fémek
Nucleic acids and their components
nucleic base: N-donors
phosphate: O-donors
soft metal ions
hard metal ions
![Page 26: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/26.jpg)
N
N N
N
MM2+ + H2P MP + 2 H+
Order of stabilitiesMg(II) < Zn(II) < Cu(II) < Fe(II) < Ni(II) < Pd(II) < Pt(II)
N = 4 (Ni(II), Pt(II), Pd(II)) – all coordination sites are occupiedN = 6 (Fe(II), Co(II), Mg(II), Zn(II)) – axial coordination site
Metalloporphyrines
![Page 27: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/27.jpg)
Complexes of alkali metal ions
No stable complexes with “normal” ligands
Crown ethers: macrocyclic polyethers
18-crown-6 Dibenzo-crown-6
OO
O
OO
O OO
O
OO
O
![Page 28: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/28.jpg)
cryptand e.g. 2,2,2 NO O
NO OO O
Li+ complex of 12-crown-4
Complexes of alkali metal ions
![Page 29: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/29.jpg)
Factors influencing the stability of alkali complexes
O
O O
O
OO
O
OO
O
a) the size of cavity
K+> Rb+> Cs+ > Na+> Li+
lgβNa(I) = 2.2 (methanol)lgβK(I) = 1.3 (methanol)
lgβNa(I) = 4.1 (methanol)lgβK(I) = 5.9 (methanol)
![Page 30: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/30.jpg)
NO O
NO OO O
( )m( )n
( )n(vízben) lgβLi(I) lgβNa(I) lgβK(I)
m=0, n=1 5,3 2,8 <2,0
m=1, n=0 2,5 5,4 3,9
m=n=1 <2,0 3,9 5,4
m=1, n=2 <2,0 1,65 2,2
m=2, n=1 <2,0 <2,0 <2,0
m=n=2 <2,0 <2,0 <2,0
a) the size of cavity
Factors influenced the stability of alkali complexes
![Page 31: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/31.jpg)
c) number of binding side
lgβNa(I)=6,95 lgβK(I)=9,45
NO O
NO OO O N
O ON
O O
lgβNa(I)=3,0 lgβK(I)=4,35
Factors influenced the stability of alkali complexes
methanol/water = 95/5
![Page 32: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/32.jpg)
d) type of binding side
OO
O
OO
O
ON
O
ON
O
CH3
CH3
Factors influenced the stability of alkali complexes
lgβNa(I) = 4.3 (methanol)lgβK(I) = 6.1 (methanol)
lgβNa(I) = 3.7 (methanol)lgβK(I) = 5.3 (methanol)
![Page 33: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/33.jpg)
d) type of binding side
NO O
NO OO O N
N NN
O OO
CH3 CH3
O
Factors influenced the stability of alkali complexes
lgβNa(I) = 3.9 (water)lgβK(I) = 5.4 (water)
lgβNa(I) = 2.5 (water)lgβK(I) = 2.6 (water)
![Page 34: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/34.jpg)
Selectivity of ligands
NO O
NO OO O
Importance• specific chelators (diagnostic, therapy)• phasetransfer: transport of KMnO4 in organic phase
![Page 35: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/35.jpg)
Complexes of alkali earth metals
O-donor ligands are preferred• crown ethers, macrocyclic• edta
NCOOH
COOHHOOC
HOOCCH2CH2N
ON
O
O
N O
O
O
O
O
![Page 36: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/36.jpg)
Alkali and alkali earth metal ions:biological roles
Abundance in human body• cca 1 % of body (trace elements < 0,01 %)• e.g. 170 g potassium/ 70 kg, 1000-1250 g Ca, 26 g Mg
• bulk elements: C, H, O, N, S, PNa, K, Ca, Mg, Cl
![Page 37: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/37.jpg)
Distribution (mmol/1000 g)
22.0440.0Extracellular fluid of neuron
410.049.0Intracellular fluid of neuronCalamary
2.51.55.0152.0blood plasma0.12.592.011.0blood cell
Ca2+Mg2+K+Na+
Alkali and alkali earth metal ions:biological roles
![Page 38: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/38.jpg)
Membrantransportprocesses
Alkali and alkali earth metal ions:biological roles
![Page 39: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/39.jpg)
Membrantransport processesTransport across the membrane
Diffusion: non-selective, in direction of concentrationgradient
Facilated passive transport: by means of carriers (ionophors)energy is not required
Active transport: in opposite direction of contentrationgradient, energy is requiredenergy source: hydrolysis of ATP
Alkali and alkali earth metal ions:biological roles
![Page 40: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/40.jpg)
Membrantransport processesTransport across the membrane
Alkali and alkali earth metal ions:biological roles
![Page 41: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/41.jpg)
Membrantransport processesTransport across the membrane
Diffusion: non-selective, in direction of concentrationgradient
Facilated passive transport: by means of carriers (ionophors)energy is not required
Active transport: in opposite direction of contentrationgradient, energy is requiredenergy source: hydrolysis of ATP
Alkali and alkali earth metal ions:biological roles
![Page 42: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/42.jpg)
Membrantransport processesTransport across the membrane
Alkali and alkali earth metal ions:biological roles
![Page 43: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/43.jpg)
Membrantransport processesPassiv transportLigands: carrier ionophors: e.g. Valinomicin
Alkali and alkali earth metal ions:biological roles
![Page 44: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/44.jpg)
Chanel ionophorse.g. Gramicidin A
![Page 45: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/45.jpg)
Membrantransport processesTransport across the membrane
Diffusion: non-selective, in direction of concentrationgradient
Facilated passive transport: by means of carriers (ionophors)energy is not required
Active transport: in opposite direction of contentrationgradient, energy is requiredenergy source: hydrolysis of ATP
Alkali and alkali earth metal ions:biological roles
![Page 46: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/46.jpg)
Membrantransport processesTransport across the membrane
Alkali and alkali earth metal ions:biological roles
![Page 47: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/47.jpg)
Biological rolesNa+, K+:• maintaining of osmotic pressure of cells• take part in acid-base processes• regulation of membrane potentials• K+: take part in determination of conformation of biomolecules, in activation of enzymes, in synthesis of acetilcoline• Na+: take part in activation of enzymes, in secondary active transport
Alkali and alkali earth metal ions:biological roles
![Page 48: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/48.jpg)
Biological roles of alkali metals
Na+, K+: regulation of membrane potentials
![Page 49: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/49.jpg)
Na+, K+: regulation of membrane potentials
Biological roles of alkali metals
![Page 50: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/50.jpg)
![Page 51: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/51.jpg)
![Page 52: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/52.jpg)
Ca2+:• regulation the processes of nerve transmission• regulation the muscle contraction• regulation electrolyte balance• blood coagulation• building up bones and theeths
Biological roles of alkali earth metals
![Page 53: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/53.jpg)
Ca2+: regulation the processes of nerve transmission
Biological roles of alkali earth metals
![Page 54: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/54.jpg)
P1
ADP
Ca2+: muscle contraction
![Page 55: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/55.jpg)
Ca2+-binding proteins• trigger proteins: e.g.: calmodulin
Buffer proteins: pl. calbindin• Ca-storage proteins: calreticulin, calsequestrin• blood coagulation: prothrombin• building up bones: osteocalcin: Ca5(PO4)3OH
![Page 56: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/56.jpg)
Ca2+-binding proteins: blood coagulation - protrombin
Biological roles of alkali earth metals
![Page 57: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/57.jpg)
Mg2+:• activation of enzymes, determination of conformation of proteins• take part in hydrolysis of ATP, universal source of energy → metabolism of energy • building up of bones• part of chlorophyll (photosynthesis)
Biological roles of alkali earth metals
![Page 58: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/58.jpg)
Mg2+ - photosynthesis
6 CO2 + 6 H2O = C6H12O6 + 6 O2
Two photosystemI. reduction of CO2 (dark reaction)CO2 + NADPH + H+ + ATP → C6H12O6
+ ADP + Pi + NADP+
II. photolysis of water (light reaction)H2O + NADP+ + Pi + ADP
O2 + NADPH + H+ + ATP⎯⎯→⎯light
chlorophyll
Biological roles of alkali earth metals
![Page 59: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/59.jpg)
Mg2+ - photosynthesis
Biological roles of alkali earth metals
![Page 60: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/60.jpg)
Mg2+ - photosynthesis
90Sr – radioactive, t½ = 28 year, can be built up in bonesBaSO4 – contrast compound (X-ray)
Biological roles of alkali earth metals
![Page 61: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/61.jpg)
Complexes of iron(II)
Complexes:• in solution: [Fe(H2O)6]2+ (octahedral, pale green)• easy oxidation to iron(III) (in basic solution)• redoxpotential of Fe(III)/Fe(II) is changed by formation of complexesFe3+/Fe2+ : CN– +0,36 V
H2O +0,77 VPhen +1,12 V
![Page 62: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/62.jpg)
Complexes:• intermediate (hard/soft) acid: binding to O-, N- and S-donor-atoms
• most important ligands: aromatic nitrogen donors in chelatable position• bipiridine, fenantroline, porphyrins
• usually octahedral complexes (some tetrahedral complexes)
Complexes of iron(II)
![Page 63: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/63.jpg)
Complexes:• in solution: [Fe(H2O)6]3+ (pale violet)• stable complexes in acid and basic pH range• characteristic reaction: hydrolysis
pH > 1: [Fe(H2O)6]3+ + H2O [Fe(H2O)5(OH)]2+ + H3O+
Ks = 1,8⋅10–3
• Dimerization → structure with oxo bridges (yellow)[(H2O)5Fe–O–Fe(H2O)5]4+
Complexes of iron(III)
![Page 64: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/64.jpg)
Complexes:pH > 2: polynuclear structures, mixed hydroxo complexes →Fe(OH)3 precipitation
• usually octahedral complexes• hard acid: • binding to F– and O-donors containing ligands• [Fe(SCN)4]– + 6 F– [FeF6]3– + 4 SCN–
intensive red colorless
Complexes of iron(III)
![Page 65: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/65.jpg)
Biological role of iron
Iron proteins
Hem proteins Non-hem proteins~ 70 % ~ 30 %
iron-sulphur othersproteins
• Human body: cca. 4 g iron (~3 g in hemoglobin)• uptaking of iron: 1 mg/day
![Page 66: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/66.jpg)
Iron proteins
Hem proteins Non-hem proteinsoxygen transport, storage
hemoglobin hemerythrinmyoglobin
electron transfercytochromes iron-sulphur proteins
oxidases, oxygenasescytochrome c oxidase
iron transport transferriniron storage ferritin
Biological role of iron
![Page 67: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/67.jpg)
Globin: contains153 amino acidsHem: Fe-porphyrin
Hem is bound to globin protein via iron ion (without covalent bound)
5. coordination side:imidazole N
Myoglobin (oxygen storage)
![Page 68: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/68.jpg)
Hemoglobin (oxygen transport)
It contains 4 globin units
Fe(II) + O2: iron ion passes to porphyrin ring
![Page 69: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/69.jpg)
uptaking of oxygen: high partial pressure of oxygengiving down of oxygen: low partial pressure of oxygenCO2 + H2O HCO3
– + H+
Hemoglobin (oxygen transport)
parital pressure of oxygen in the lungs
partial pressure of oxygen in the muscle
![Page 70: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/70.jpg)
– oxygen transporter in molluscs
– 4 part, one part contain two iron, it binds one O2
Hemerythrin
![Page 71: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/71.jpg)
• transfer electrons (redox proteins and enzymes)• insert oxygen atoms or dioxygen into organic substrates or catalyse other important organic reaction• coordination number: 5 or 6• interaction between protein and hem moiety: covalent or van der Waals bound
Cytochromes
![Page 72: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/72.jpg)
Cytochrome C
provide electrons via following reaction:
Fe2+ Fe3+ + e–
![Page 73: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/73.jpg)
Cytochrome P450• part of monooxygenase enzymes • activation of dioxygen molecule
RH + O2 + 2 e– + 2 H+ → ROH + H2O
• 5. coordination side: cysteine S • 6. coordination side: H2O
Cytochromes
![Page 74: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/74.jpg)
Cytochrome P450
![Page 75: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/75.jpg)
Catalase– catalysing the disproportion of H2O2
2 H2O2 → 2 H2O + O2
– it contains four same units– 5. coordination side: tyrosine O–
– mechanism:
Fe(III)
O-(Tyr)
Fe(IV)
O-(Tyr)
H2O2 H2O
H2O2H2O + O2
![Page 76: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/76.jpg)
Catalase
![Page 77: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/77.jpg)
• Tetrahedral geometry of iron• Iron binding to inorganic and organic sulphur donors (Cys) S• one e–-pass
• reduced ferredoxin oxidized ferredoxin • unusually low redox potenctial: –0,05 - –0,49 V → they behave as a reduction agents
Iron-sulphur proteins
• rubredoxin: [1Fe]3+(RS–)4 (–0,06 V)• ferredoxins: [2Fe-2S]2+(RS–)4 (–0,3 - –0,4 V)
[4Fe-4S]2+(RS–)4 (–0,4 V)HIPIP: [4Fe-4S]2+(RS–)4 (0,35 V)
– e–
+ e–
![Page 78: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/78.jpg)
Iron-sulphur protein (HIPIP)
![Page 79: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/79.jpg)
Iron-sulphur proteins
![Page 80: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/80.jpg)
Transferrin:Transport: iron(III) form, at neutral pHStructure: M ~ 80.000, 0,15 % irontwo structural units:
one unit: 2 iron(III) + protein
Transport of iron
![Page 81: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/81.jpg)
Siderophores:iron transporter in microorganisms
C
N
R
R
O
O-
Fe+3
3
O-
O-
Fe+3
3
Rhydroxamate-type
e.g. ferrichromcatecholate-type
e.g. enterobactin
Transport of iron
![Page 82: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/82.jpg)
FerritinIt contains 24 protein units (~ 175 amino acids/unit)4500 iron atoms/ferritin (25 %)iron micelle (7 nm diameter) : (FeOOH)8⋅FeO⋅H2PO4
uptaking: iron(II) form, it is followed by oxidation to iron(III)Hemosiderinstorage of excess of ironcca. 45 % iron
Storage of iron
![Page 83: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/83.jpg)
![Page 84: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/84.jpg)
Biological role of copper
• Essential for every living organisms• 80-120 mg / 70 kg body• uptaking: 1,5-3,0 mg/day, < 10 mg• toxicity: > 15 mg• diseases caused by copper:
excess of copper: Wilson diseasemissing of copper: Menke’s disease
![Page 85: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/85.jpg)
Functions of copper proteins
• Oxygen transport, storage: hemocyanin (mollusc)
• Catalysing of redox processesoxidases (blue-copper oxydase), oxygenases, superoxide dismutase
• Copper transport, storage: ceruloplasmin, metallothionein
Biological role of copper
![Page 86: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/86.jpg)
Superoxide dismutase (SOD)2 O2
– + 2 H+ H2O2 + O2⎯⎯→⎯SOD
His 61
His 78
His 69
H2O
Zn2+
Cu2+
His 44
His 46His 118
Asp 81
Biological role of copper
![Page 87: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/87.jpg)
Superoxide dismutase (SOD)Zn: regulation of structureCu: takes part in redox processes
Reactions:Cu2+(His–)Zn2+ + O2
– + H+ → Cu+ + (HisH)Zn2+ + O2
Cu+ + O2– + H+ + (HisH)Zn2+ → Cu2+(His–)Zn2+ + H2O2
Biological role of copper
![Page 88: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/88.jpg)
Ceruplasmine:1005 amino acid (single protein chain), 6 copper
Function: • oxidase• ferrioxidase: Fe2+ → Fe3+
• transport of copper• metabolism of copper → missing of ceruloplasmine →Wilson disease, Menke’s disease
Biological role of copper
![Page 89: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/89.jpg)
Zinc metalloproteins1940 – first zinc enzyme: carbonic anhydrase1985 – 100 zinc containing enzymes1995 – 300 enzymes + > 100 zinc containing proteins
Role of zinc: • active centrum (catalysing of acid-base processes)• regulating of structure
The second most abundant trace element The least toxic elementEssential for every living organism2-4 g zinc / 70 kg body
Biological role of zinc
![Page 90: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/90.jpg)
Carboanhydrase
• Process:CO2 + H2O HCO3
– + H+
k = 3·10–2 s–1, with enzyme: k = 6·105 s–1
• Zn: tetrahedral geometry, • coordination: 3 histidine + 1 H2O• Zn – H2O → Zn-OH– → interact with CO2
Carboxypeptidase A• Process: hydrolysis of peptide bound at C-termini • 1 Zn + 307 amino acids (M ~ 34.000) • coordination: 2 histidine + 1 glutamate COO– + 1 H2O
![Page 91: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/91.jpg)
Glu 117
His 119
Thr 199
His 96
His 94
His 64
Glu 106
H2O
Gln 92
Zn2+
Carboanhydrase
![Page 92: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/92.jpg)
Carboxypeptidase A
![Page 93: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/93.jpg)
Zinc fingers
• Metalloproteins, which take part in the DNA transcription• Zn: regulation of structure• 9-10 zinc ions, • Zn2+: tetrahedral geometry (His N, Cys S) →the conformation is similar to a finger
![Page 94: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/94.jpg)
Zinc fingers
![Page 95: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/95.jpg)
Pharmaceutical application of metals
Administration of trace elements• treatment of deficiency diaseses Remove of toxic elements• treatment of toxicity of heavy metals
Important aspects:• metal complexes of chelatable or macrocyclic ligands have high stability• neither ligands nor complex are not toxic• ligand is selective
![Page 96: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/96.jpg)
Metal complexes in therapy
Anticancer pharmaceuticals, medicines:cisplatin complexes
cisplatin carboplatin
Pharmaceutical application of metals
H3NPt
H3N
Cl
Cl
H3NPt
H3N
O
O
C
C
O
O
![Page 97: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/97.jpg)
Mechanism of cisplatin
Pharmaceutical application of metals
H3N (II)Pt
H3N
Cl
Cl
H3N (II)Pt
H3N
Cl
OH2
NH3
Pt(II)H3N Guanin (DNA)
Cl
H3N (II)Pt
H3N
G
G
hydrolysis
DNA
![Page 98: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/98.jpg)
Metal complexes in therapyLithium: maniac depression: Li2CO3
Vanadium: insulin mimic (oral) pharmaceuticals
bis(picolinato)oxovanadium(IV) bis(maltolato)oxovanadium(IV)
OV
N
N
OO
O O OV
O
O
O
OO
O
CH3
CH3
Pharmaceutical application of metals
![Page 99: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/99.jpg)
Metal complexes in therapy• Bismuth: gastric ulcer: Bi(NO3)3
• zinc: treatment of ulcers
Pharmaceutical application of metals
![Page 100: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/100.jpg)
Metal complexes in therapy• gold: rheumatoid arthritis
Pharmaceutical application of metals
+Na-O
S
O-Na+
O
OAu
n
O
H
HO
H
HO
H
HOHH
S
OH
Au
Au S CH2
HC
H2C SO3Na
OH
nMyochrysine
Solganol
Allochrysine
![Page 101: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/101.jpg)
Metal complexes in therapysilver: treatment of infection
Pharmaceutical application of metals
SHN
N
N
H2N
O O
sulfadiazin
![Page 102: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/102.jpg)
Contrast compounds• X-ray contrast:
heavy metal salts: e.g.: BaSO4
organic iodine compounds• NMR tomography: Gd-polycarboxylate complexes
Pharmaceutical application of metals
![Page 103: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/103.jpg)
Contrast compounds• NMR tomography: Gd-polycarboxylate complexes
NN
N
COO-
-OOC
-OOC
COO-
COO-
N N
NNCOO-
COO-
-OOC
-OOC
DTPA - Magnevist
DOTA - Dotaterm
Pharmaceutical application of metals
![Page 104: Bulk and trace elements](https://reader030.fdocuments.us/reader030/viewer/2022020203/587759c21a28ab0f538bc3ce/html5/thumbnails/104.jpg)
Radioactive isotopesDiagnosis• > 80 %, 99mTc, γ-ray (t1/2(γ) = 6 hours, t1/2(β) = 212000 years)
Therapy• outer ray source• Injection: 186Re, 188Re
Pharmaceutical application of metals