Biochemistry of Minerals

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Biochemistry of Minerals
P
C
N
H
O
S
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
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Characteristics of Biochemical Ion Complexes
Na, K Mg2,Ca2 Zn2, Ni2
Fe, Cu, Co, Mo, Mn
Favored Oxidation state 1 2 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 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
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Inorganic Enzyme Cofactors (one-third of all
enzymes require a metal ion for catalytic
function)
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Metalloenzymes vs Metal Activated Enzymes
Metal Activated
Metalloenzyme
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
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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
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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 Genet
ic 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 Morphogenes
is Gene regualtion
Cu, Cu2
Enzyme cofactor Oxygen carrier Oxygen
activator Iron metabolism
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Quick Overview (cont.)
Se
Cr3
Insulin mimetic Glucose metabolism
Redox reactions Antioxidant
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
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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
Selenium transport
5. Selenoprotein W
6. Calbindin
Calcium transport
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Biomineralization
Calcium and phosphate
Bones and Teeth
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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.
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Demineralized bone Shown is he organic matrix
consisting mostly of collagen upon which the bone
crystals are laid.
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Hydroxyapatite (crystal structure) Ca10(PO4)6
OH2
Ca
P
O
H
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Zinc Function

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

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Metal Ions in Catalysis- One third of all
enzymes require a metal ion for catalysis
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Zn 2Polarizes H2O, making it a better nucleophile
H2O
Displaces HCO3-
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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

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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

All use O2 as a substrate
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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 2H2O
Peroxidase
2H2O2 ? 2H2O O2
(O2 is either incorporated into the product or
reduced by electrons)
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Electron Transport Complexes

• Membranes bound heme proteins or cytochromes
• Iron-Sulfur proteins..high reducing potential
• Mobile electron carriers
• Coenzyme Q
• Cytochrome c

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Transport Mechanism
A bucket-brigade
NADH
0.82 volts
-0.32 volts
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Iron and Molybdenum in Nitrogenase
Fe
N2 3H2 ? 2NH3