METAL IONS IN BIOLOGY

A.I.Anu Karthi SwaghathaB443002

OBJECTIVES

To understand the role of metal ions in biology

To know something regarding the Na-K pump

CONTENTS

A Complex Life...ClassificationMetals in BiologyWhat Are Their Roles?Ultra trace ElementsConclusion

A COMPLEX LIFE…Life’s a metal ionMetals from s- and d- block acts as active sites in

majority of the enzymesFe , Zn and CuMetal-containing biomolecules-very much

important

CLASSIFICATION OF ELEMENTS

ESSENTIAL

NONESSENTIA

L

ELEMENTS

ESSENTIAL ELEMENTS

• Required for the maintenance of life of plants & animals

• Absence causes death or severe malfunction

NON ESSENTIAL ELEMENTS

• Don’t play any positive role in biological systems

TOXIC ELEMENTSELEMENTS AVERAGE

QTY (mg)EXCESS OF QUANTITY

As 18 cancerous

Sn 6.0 cancerous

Bi 0.2 cancerous

Te 0.1 cancerous

Pb 121 Plumbism

Cd 5.0 High B.P.

Sb 8.0 Poisoning

Be 0.04 Causes heart disease

Cr (VI) 1.5 cancerous

Periodic Distribution of Biologically Important Elements

METAL IONS IN BIOLOGYOccur in several formsMost advanced class- Metalloenzymes or

BIOLOGICAL CATALYSTSSpecific roleMajor- d-block elementsBut s-block elements are also important – -Structural role (Ca) -Enzymatic action(Mg) -Homeostatic balance (Na & K)

WHAT ARE THEIR ROLES???

s-block metalsBulk metals- K, Na, Mg and Ca

Maintain electrical charges

Osmotic pressure

Prevents the cells from collapsing by making it turgid

Na+

Major cation of the extracellular fluidCreates electrical potential for the functioning of

nerve cells & muscle cellsNa+ - 0.01 MNa+ ions also serves as essential activating ions for

specific enzyme activityAssociated with acid-base balance

K+

K – 0.15 M Electrolytic balance Proper functioning of heart Maintainenance of blood pressure Nerve impulses Aids in the waste removal process Enhances the muscle functioning In the synthesis of ribosomes

TRANSPORTATION OF IONS• Charged Ions must pass through a Hydrophobic

Membrane– Neutral gases (O2, CO2) and low charge density

ions (anions) can move directly through the membrane

– High charge density cations require help

MECHANISMS• Ionophores: special carrier molecules that wrap

around metal ions so they can pass through the membrane by diffusion

• Ion Channels: large, membrane-spanning molecule that form a hydrophilic path for diffusion

• Ion Pumps: molecules using energy to transport ions in one direction through a membrane

TYPES• Passive Transport: moves ions down the concentration

gradient, requiring no energy source– Ionophores and Ion Channels are Passive

• Active Transport: moves ions against the concentration gradient, requiring energy from ATP hydrolysis– Ion Pumps are Active

• Choice of Transport Mechanism– Charge– Size– Ligand Preference

Sodium and Potassium Ion Pump• Na+/K+-ATPase– Membrane-Spanning Protein Ion Pump– a2b2 tetrameric 294,000 dalton protein– Conformational changes pump the ions: one conformation

binds Na+ best, the other binds K+ best– Hydrolysis of ATP provides the energy for conformational

changes (30% of a mammal’s ATP is used in this reaction)– Antiport transport: like charged ions are transported in

opposite directions– Reversing the normal reaction can generate ATP– Reaction can occur 100 time per second– 3Na+in + 2Kout+ + ATP4- + H2O 3Na+out + 2K+in + ADP3-

+ HPO42- + H+

Sodium and Potassium--Ionophore• Nonactin: microbial Na+ and K+ ionophore• Makes Na+ and K+ membrane soluble when complexed• Oxygen Donors can be modeled by Crown Ethers

OOO

O

O O O

O

CH3

O

CH3CH3

O CH3CH3

O

CH3CH3

OCH3

Sodium and Potassium--Ion Channel• Gramicidin: ion channel-forming molecule– Helical peptide dimer– Hydrophobic outer surface interacts with membrane– Carbonyls and Nitrogens on inner surface can interact with

cations as they pass through– Potassium selective: pore size and ligands select for K+

• Channels can be Voltage-Gated or activated by the binding of a Chemical Effector which changes the conformation

• 107-108 ion/second may pass (Emem = 100 mV)

Mg2+

Mg2+

- chlorophyll - intracellular fluids - carbohydrate metabolism - enhances nerve impulses (extracellular fluid) - Active site of transferase, phosphohydrase

Ca2+

-Bone formation-- Brain functioning-Maintains the heart rhythm-- Blood clotting -Formation of teeth enamel (fluoroapatite) -1000 times less in intracellular fluids

d-block elements

VANADIUM - extremely small amounts - lichens & fungi have it in the active site of enzymes - appears in nitrogenase, vanadium (v) in

haloperoxidasesCHROMIUM Cr(III) – mammals - lipid and glucose metabolism - glucose tolerance Cr(VI) & Cr(V) – mutagenic and carcinogenic, Cr(V)

damages DNA - normal secretion of insulin

MANGANESE - in wider range of organisms - in important enzymes and

processes(photosynthesis) - Mn (II) and Mn(III) have redox role Eg: In the enzyme superoxidedismutase (SOD)

IRON - Truly ubiquitous - Required for tissue growth - Responsible for oxygen transport - In humans Hb & Mb represent 65% & 6% of all Fe in

body - Ferritin- rapid access to Fe

SOMETHING ABOUT FERRITIN• Structure:– symmetric, spherical protein coat of 24 subunits• Subunits are 175 amino acids, 18,500 daltons each• Channels on 3-fold axes are hydrophilic: iron entry• Inside surface is also hydrophilic

– Inner cavity• 75 Å inner diameter holds 4500 iron atoms• Iron stored as Ferrihydrate Phosphate

[(Fe(O)OH)8(FeOPO3H2) . nH2PO4]

– Iron-protein interface: binding of core to protein is believed to be through oxy- or hydroxy- bridges

Pathway of Fe2+ from food stuffs to Hb and ferritin involves the following mechanism

COBALT - essential in small amounts - cobalamines are found in many organisms (5 mg

in humans) -enzymes with inert Co (III) has been discovered,

provides labile reaction sites - extremely toxic to plants NICKEL - An important component in urease,

carbonmonoxide dehydrogenase and methyl-S-coenzyme M reductase

- Exists in oxidation states like I , II, III

COPPER - present at the active site of a large

number of enzymes - 3rd most abundant transition element - as electron transfer agentsEg: cytochrome C oxidase , tyrosinase,

nitrite reductase - blue copper proteins(type-1) - in Hb formation

ZINC - Adults 2-3 g - carbonic anhydrase, carboxypeptidase - 300 known enzymes - DNA binding proteins - zinc reserves - Maintains normal concentration of Vit-A - Tissue repairing & wound healing

Symptoms of Elemental Deficiency in Humans __________________________________________________________Ca Retarded skeletal growthMg Muscle crampsFe Anemia, immune disordersZn Stunted growth, skin damage, retarded maturationCu Liver disorders, secondary anemiaMn Infertility, impaired skeletal growthMo Retarded cellular growthCo Pernicious anemiaNi Depressed growth, dermatitisCr Diabetes symptomsSi Skeletal growth disordersF Dental disordersI Thyroid disordersSe Cardiac muscular weaknessAs Impaired growth (in animals)________________________________________________________

ULTRATRACE ELEMENTSNeeded at less than 1 ppm or 50 ppb

Includes As, B, Si, Ni, V in humans

Other elements include Br, Cd , F , Pb , Li, Sn

Quite toxic at any concentration much above concentrations ultra trace level

WHY CARBON INSTEAD OF SILICON?

CONCLUSIONLife evolved utilizing these elements that are

abundant & available to it and became dependent upon them

Rare elements are not utilized….

REFERENCE Huheey J E, Keiter A Ellen, Keiter L Richard, Medhi K Okhil, “Inorganic

Chemistry-Principles of Structures and Reactivity”, 4th edition, Pearson Lawrance A Geoffrey, “Introduction to Coordination Chemistry”,2010,

Wiley Puri, Sharma and Kalia, “Principles of Inorganic Chemistry”,31st edition,

Milestone J D Lee, “Concise Inorganic Chemistry” , 5th edition, Wiley

TIME TO QUERIES …

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