1. Biochemistry of MineralsP Na K Ca Mg Cl
Biological forms of minerals in living systems Fe Zn Cu Mn Se Co V Si As Mo I Br F

2. Characteristics of Biochemical Ion Complexes
Na+, K Mg2+,Ca Zn2+, Ni2+ Fe, Cu, Co, Mo, Mn
Favored Oxidation state +1 +2
Variable, more than one state
Stability of complex
Very low
Low to medium
High
High (medium for Mn2+ and Fe2+)
Favored donor atoms
Oxygen
Sulfur or nitrogen
Sulfur or nitrogen (oxygen for Mn and Fe)
Mobility in biological media
Very mobile
Semi mobile
Static
Static, semi mobile for Mn2+ and Fe2+
After Frausto de Silva and Williams

3. Glucose Na+ Mg2+ Mn2+ K+ Ca2+ PO43- Hemoglobin O2 Fe2+ H2O Cu2+
intestine
Na+
liver
Mg2+
Mn2+ K+
Ca2+
PO43-
mitochondria
Hemoglobin O2
Fe2+
H2O
Cu2+

4. Inorganic Enzyme Cofactors
(one-third of all enzymes require a metal ion for catalytic function)

5. Metalloenzymes vs Metal Activated Enzymes
1. Metal in equilibrium
Metal firmly affixed to protein
2. Activated by adding metal ion
Adding metal has minimal effect
3. Metal lost on isolation
Metal stays bound, removable by chelators
4. No stoichiometry with protein
Integral number per protein
5. Electrostatic bonding
Coordinate covalent bonding
6. Multiple metal binding sites
Limited number, generally one
7. Binding sites, angles irregular
Binding sites exhibit specific geometry
Mostly group IA and IIA metals
Na+, K+, Mg2+. Ca2+
Mostly 3d transition metals
Zn2+, Fe2+. Cu2+, Co2+

6. Examples of Metalloenzymes
Zinc (over 300)
Manganese
Arginase
Water splitting enzyme
Pyruvate carboxylase
Dehydrogenases
RNA, DNA polymerase
Carbonic anhydrase
Carboxypeptidase
Amino peptidase
Cobalt (with B12)
Methylmalonyl CoA mutase
Homocysteine transmethylase
Copper
Superoxide dismutase
Tyrosinase
Cytochrome oxidase (with Fe)
Lysyl oxidase
Peptide amidating
Dopamine beta hydroxylase
Molybdenum
Nitrogenase
Xanthine oxidase
Calcium
Iron
Thermolysin
Ribonucleotide reductase
Cytochrome oxidase (with Cu)
Nickel
Urease

7. Quick Overview of Mineral Functions
Zn2+
Na+, K+, Cl-
Osmotic control
Electrolyte equilibria
Ion currents
Gated channels
Lewis acid
Enzyme cofactor
Protein structure
Hormone activator
Neurotransmitter
Genetic expression regulator
Mg2+
Fe2+, Fe3+
Phosphate metabolism
Heme iron
Electron transport
Oxygen activator
Oxygen carrier
Ca2+
Muscle contraction
Cell signaling
Enzyme cofactor
Blood clotting
Mineralization
Morphogenesis
Gene regualtion
Cu+, Cu2+
Enzyme cofactor
Oxygen carrier
Oxygen activator
Iron metabolism

8. Quick Overview (cont.) Se Cr3+ Redox reactions Antioxidant
Insulin mimetic
Glucose metabolism
Mo2+
Mn2+
Enzyme cofactor
Nitrogen activator
Enzyme cofactor (limited)
HPO4=, Si
Ni2+
Coenzyme
Remnant of early life
Acid-base non metals
Biomineralization
Co3+
Vitamin b12

9. Examples of Metalloproteins
Function
1. Metallothionein
Cu, Zn, Cd storage, heavy metal buffer
2. Ferritin
Iron storage, iron buffer
3. Calmodulin
Ca binding, allosteric regulator
4. Transferrin
Iron transport
5. Selenoprotein W
Selenium transport
6. Calbindin
Calcium transport

10. Biomineralization
Calcium and phosphate
Bones and Teeth

11. Cross section through trebecular and cortical bone revealing the internal architecture surrounded by marrow tissue.
Cortical bone with Halversion system (a series of channels supplying nutrients). Black dots are osteocytes
Leg bone of a horse showing the trebecular (spongy) bone and the cortical (solid) bone. This bone is able to withstand forces generated by this 1,500 lb animal
Trebecular bone of the lower spine. Changes with aging.

12. Demineralized bone: Shown is he organic matrix consisting mostly of collagen upon which the bone crystals are laid.

13. Hydroxyapatite (crystal structure)
Ca10(PO4)6 OH2 Ca P O H

14. Zinc Function 300 enzymes require zinc numerous hormones require zinc
DNA, RNA polymerases
numerous hormones require zinc
insulin
EGF
transcription factors (zinc finger proteins)
membrane stability
myelination
skeletal development

15. Metal Ions in Catalysis-
One third of all enzymes require a metal ion for catalysis

16. Zn 2+Polarizes H2O, making it a better nucleophile
His –Zn2+
His O H ..
+ C
His –Zn2+
His O H C
H2O
His –Zn2+
His O H ..
+ H+
+ H C
Bicarbonate
Displaces HCO3-

17. Biochemical Iron Hemoglobin- oxygen carrier in the blood
Myoglobin- O2 carrier in cells (mostly in muscle)
Cytochromes- electron carriers in membranes
Catalase- enzyme that destroys H2O2 (hydrogen peroxide)
Cytochrome oxidase- electron transport, ATP synthesis in mitochondria
Cytochrome P450- detoxifying enzyme
Nitrogenase- nitrogen fixation
Ferritin- iron storage in cells, plasma
Transferrin- iron transport in blood
Iron-sulfur electron proteins- electron carriers
Tyrosine and phenylalanine hydroxylase- enzymes that synthesizes L-DOPA and tyrosine, respectively
Ribonucleotide reductase- enzyme that forms deoxyribose from ribose

18. Function Oxygen Transport & Storage
Hemoglobin
Myoglobin
Electron Transport & Energy Metabolism
Cytochromes
Fe-S proteins
Substrate Oxidation & Reduction
– Iron dependent enzyme-
Ribonucleotide reductase
Amino acid oxidases
Fatty acid desaturases
Nitric oxide synthetase
Peroxidases
HEME is synthesized in the liver from succinyl-CoA and Glycine.
Hemoglobin represents more than 95% of the proteins of the red blood cell, and contains about 60% of the body iron.
Function1) transport O2from the respiratory organ to peripheral tissue
2)Transport of CO2 and proteins from peripheral tissues t the lung for subsequent excretion
3)transport NO. 2,3-bisphosphoglycerate, an intermediate in glycolysis, stabilizes the tettrameric structure of hemoglobin, indicateing another important function of glycolysis in the functions of red blood cells. (Iron dificient, heme decreases leading O2 transport and NO transport decrease--- Vascular systeem decreases and immune system decrease)
Myoglobin is a single polypeptide chain (MW16900). Contains about4% of the body’s iron. Myoglobin is the minor protein of muscle cells and is used for the short term storage of oxygen.
Electron transport: In cytochromes, the oxidation and reduction of the iron atom are essential to their biological function. By contrast, oxidation of the Fe2+ to Fe3+ of hemoglobin or myoglobin destroys biological activity.
All use O2 as a substrate

19. Examples of Iron-dependent Enzymes
Aldehyde Oxidase
R-CHO + O2  RCOOH + H-O-O-H
Tryptophan 5-monooxygenase
L-tyrptophan + BH4 + O2  5 OH L-tryptophan + BH2 + H2O
Fatty Acid desaturase
Stearoyl-CoA + NADH + H+ + O2  Oleoyl-CoA + NAD H2O
Peroxidase
2H2O2  2H2O + O2
(O2 is either incorporated into the product or reduced by electrons)

21. Electron Transport Complexes
Membranes bound heme proteins or “cytochromes”
Iron-Sulfur proteins..high reducing potential
Mobile electron carriers
Coenzyme Q
Cytochrome c

22. .. .. .. .. .. .. .. .. Reduced Oxidized Transport Mechanism
A bucket-brigade .. ..
Cyt
a+a3
(Fe3+)
(Fe2+) .. ..
Cyt b
(Fe3+)
(Fe2+)
Cyt c1
(Fe3+)
(Fe2+)
Cyt c
(Fe3+)
(Fe2+)
NADH
FMN
FMNH2
CoQ
CoQH2 O2
H2O
NAD+ .. .. .. ..
Reduced
Oxidized
volts
-0.32 volts

25. Iron and Molybdenum in Nitrogenase- H N = 2 F d e R A T P D . 9 4 3 c t i v a
Electron Transfer “Pump”
Dinitrogenase
Dinitrogenase Reductase
e + H+ Fe
N2 + 3H2  2NH3