TRANSITION ELEMENTS IN BIOLOGY,

OCCURRENCE, BENEFICIAL AND

TOXIC EFFECTS OF METAL IONS

Anjana Rajeev K
P190042CY
 Classification of elements in biological system

1.Essential metals

a)Bulk
-Na, K, Ca, Mg

b)Trace metals
-Fe,Zn,Cu

c)Ultra trace metals

- Mn, Mo, Co, Cr, V, Ni, Sn,Li

2.Non-essential metals
-Hg, Pb,Cd, Al and others
 FUNCTION OF BULK METALS
Calcium
• 1.5-2% of body mass.
• Strengthening of bones and teeth
• muscular activity
• blood coagulation
• cellular permeability.

Sodium
• Active in hydrosaline equilibrium
• transmission of nervous impulses and
transport of
metabolites.

Magnesium
Potassium
• In bones and teeth, together with Ca
• Maintenance of water balance and fluids inside and
• activation of muscular contractions
outside cells
• body temperature control
• muscular contractions and nervous impulses.
• component of several enzymes.,
• intracellular activity
 FUNCTIONS OF TRACE METALS
Iron
• Part of hemoglobin, which carries oxygen in the blood
• Part of myoglobin in muscles, which makes oxygen available
for muscle contraction
• Necessary for the utilization of energy as part of the cells
metabolic machinery
Zinc
• Occurs in all tissues, mostly in bones, muscles and skin
• active in the immunological system
• regulates body growth
• protects the liver
• Part of many enzymes
• Associated with the hormone insulin
• Involved in making genetic material and proteins, transport of vitamin
A,taste perception, wound healing and the normal development of the
fetus
Copper
• various roles in biological electron transport and oxygen
transportation.
• Component of various oxidizing enzymes during metabolism
of energy
sources
• active in the synthesis of hemoglobin
 FUNCTIONS OF ULTRA TRACE METALS
Manganese
• Promotion of growth and development
• cellular functions
• takes part in metabolic reactions. Chromium
• Cofactor of many enzymes. • Needed for metabolism of sugar by binding
and potentiating insulin

Cobalt
Vanadium
• Active in vitamin B12 and in chemical
• Essential. Extends teeth life
reactions.

Molybdenum
Selenium
• Cofactor for several enzymes
• Defends against oxidation
• Regulates thyroid hormone
Nickel
• part of many enzymes like urease

METALS ARE AN INTEGRAL PART OF MANY STRUCTURAL AND FUNCTIONAL COMPONENTS IN THE BODY
BUT…….
 Toxicity
Toxicity of metals stems from the fact that they are biological non-degradable and have a
tendency to accumulate in vital organs.
e.g. brain, liver, etc. and their accumulation become progressively more toxic

Factors that Affect Metal Toxicity

• Level and duration of exposure Two Classes of Toxic Metal Compounds
• Chemical form of metal • Accidental ingestion of the element or from
• Metal-protein complexes metabolic disorders leading to the
• Host factors incapacitation of normal biochemical
1. Lifestyle mechanisms
2. Gender • The other broad class results from entry of
3. Age nonessential metals into the cell through food,
4. Immune status skin absorption, or respiration.

• Biochemical mode of action of metal

toxicity: inhibition of enzymes
Affinity for-SH (sulfhydryl groups)
• Occur in enzymes which control metabolic
pathways
M2+ + 2 R-S-H → R-S-M-S-R + 2H+
 Copper Overload and Wilson's Disease

• Wilson's disease results from a genetically inherited metabolic

defect in which copper can no longer be tolerated at normal
levels.

• The clinical manifestations are liverdisease,neurological

damage, and brown or green rings in the cornea of the eyes.

• Patients suffering from Wilson's disease have low levels of

the copper-storage protein ceruloplasmin.
 Iron Toxicity
•Acute iron poisoning, such as that resulting from accidental ingestion of FeS04 tablets,
results in corrosion of the gastrointestinal tract.

• Chronic iron poisoning, or hemochromatosis, arises from digestion of excess iron

usually supplied by vessels usedfor cooking.

• A classic case of the latter is siderosis induced in members of the Bantu tribe in South
Africa, who consume large quantities of beer brewed in iron pots and who suffer from
deposits of iron in liver, kidney, and heart, causing failure of these organs.

Iron overload: infections, fatigue, joint pain,

skin pigmentation, organ damage
 Toxic Effects of Other Essential Metals
When present in concentrations above their normal cellular levels, most of the
other metals are toxic.
• Failure to regulate Ca2+ leads to calcification of tissue, the formation of
stones and cataracts, a complex process about which little is understood.

• Chronic manganese poisoning, which can occur following ingestion of

metal-oxide dust, e.g., among miners in Chile, produces neurological
symptoms similar to Parkinson's disease.

• Although Zn toxicity is rare, it can lead to deficiencies in other essential

metals, notably calcium, iron, and copper.

• Cobalt poisoning leads to gastrointestinal distress and heart failure.

• Selenium-Loss and brittleness of hair and nails, Skin rash, fatigue,

irritability, and nervous system disorders,Garlic breath odor

• Cr-Excess may result in renal failures. Excess of Cr is carcinogenic.

• V-Excess may cause lung diseases.

 Metals as Carcinogens

•Although most metal ions have been reported to be carcinogenic, the three most effective
cancer-causing metals are Ni, Cr, and, to a lesser extent, Cd.

• Nickel subsulfide, found in many nickel-containing ores, has been extensively studied and
shown to be carcinogenic in humans and other animals.

• Chromium is most carcinogenic as chromate ion (Cr042-), which enters cells and reduced to
Cr(III) via a Cr(V)-glutathione intermediate species.

• The latter complex binds to DNA to produce a kinetically inert and potentially damaging
lesion.
 Non-essential metals are highly toxic

Al Non essential, despite its crustal abundance. Interferes with and reduces assimilation
of phosphorus, causing bone demineralization. Suspect of influencing Alzheimer disease.

Be Non essential. Toxic when inhaled as dust.

Cd Non essential. Toxic and carcinogenic. Interferes with Zn, inhibiting the normal
assimilation of Zn.

Hg Non essential. Poisonous.

Pb Non essential and toxic.

Sn Non essential and toxic.

Ti Non essential and toxic.

 Lead
• Types of lead
• Inorganic – PbO2
• Organic – Tetraethyl lead, tetramethyl lead, highy toxic as they are lipid-soluble

• Sources of exposure
• Mining/Smelting
• Cutting and welding lead-painted structure
• Manufacture/Recycling of lead storage
batteries
• Production of lead based paints

The use of unleaded gasoline and the removal of lead-containing pigments from paint have
substantially diminished the quantity of this element released to the environment each year
Transport and storage
• Pb is transported to all organs and tissue of body by blood
• 95% of Pb in blood is associated with the erythrocytes and remain with plasma
protein
• Lead accumulates in bone throughout life
• 90% of body burden of lead is found in bone and most remaining 10% in kidneys
and liver

Organ systems
• GI
• Nervous & neuromuscular
• Renal and cardiovascular
• Reproductive system – premature baby
• Signs and symptoms include
• Muscle weakness, anemia, Insomnia, loss of memory, headache, paralysis of
extensor muscles of the wrist
 Cadmium

Sources
• By-product from smelting of lead & zinc ores
• Welding
• Food & smoking

Toxic effects
• Mechanism
• Displacing or replacing zinc from the many (over 200) enzymes requiring zinc as a
catalytic or structural component
• Acute exposure to Cd fumes
• Cough, chest pain, irritation to upper Resp. tract, respiratory damage
• Death
• Chronic
• Liver damage, anaemia, teratogenic effects, renal damage
 MERCURY
Was used as “cure” for almost every ailment in the past
Incident of methyl mercury
• Minimata Bay 1953 – 1960
• Methylmercury - The highly toxic compound bioaccumulated in fish and shellfish
when eaten by the people living around the bay, gave rise to Minamata disease
• The 1971 Iraq poison grain disaster was a mass methylmercury poisoning incident
Metabolism – Three form
• Elemental – Hgo
• Inorganic : Hg+ and Hg 2+
• Organic
Absorption
• Hgo via respiratory tract (80% retained)
• Hg+ and Hg 2+ about 7% retained
• Organic Hg about 70% retained
Distribution and Metabolism
• Oxidation finally to Hg2+
• Affinity for kidney
 Biological Effects
• Central Nervous System
• Neuropsychiatric by Hgo
• Tremor, insomnia, emotional instability, depression
• Sensorimotor for organic Hg
• loss of senses, incoordination, paralysis
• Mechanism
• Disrupts metabolism and causes degeneration of neurons
• Kidney
• Mainly inorganic – tubular damage

Others
Stomatitis- inflammation of the mouth and lips
Gingivitis-non-destructive disease that occurs around the teeth.
Excessive salivation
 Biological metal-coordination sites

 The major binding sites for metal ions are provided by the amino acids that make up
protein molecules.
The ligation sites range from backbone peptide carbonyls to the side chains that provide
more specific complexation.

Metalloproteins, proteins containing one or more metal ions, perform a wide range of
specific functions.
1. Oxidation and reduction (Fe, Mn, Cu, and Mo)
2. Oxygen carriers(Fe and Cu)
3. Radical-based rearrangement reactions & methyl-group transfer (Co)
4. Hydrolysis (Zn, Fe, Mg, Mn, and Ni)
5. DNA processing(Zn)
6. Special proteins are required for transporting and storing different metal atoms
7. Metal-ion activated proteins

Metalloenzymes, this term is applied to enzymes that not only require the participation of
metal ion at the active site to function but bind that metal ion strongly even in the resting
state.
Sub-class of metalloproteins
 Co-ordination sites

All amino acid residues can use their peptide carbonyl (or amide-N) as a donor group,
but it is the side chain that usually provides more selective coordination.
Donor groups are either chemically hard or soft and that therefore confer a particular affinity
for specific metal ions.

 Aspartate and glutamate-forCa2+

 Histidine-for Fe, Cu and Zn
Cystein -Fe, Cu, and Zn as well as for toxic metals such as Cd and Hg.
 Methionine-Fe(II)andCu(I).
Tyrosine -Fe(III)).

Special ligands

1.Porphyrin
2.Corrin
 Oxygen carriers
1.Myoglobin
 Fe protein
coordinates O2 reversibly and controls its concentration in tissue.
contains several regions of helix, implying mobility.
 Single Fe porphyrin group located in a cleft between helices E and F.
The fifth ligand -histidine-N from helixF.
The sixth position - O2

The Fe in deoxymyoglobin is
• five-coordinate
• high-spin
• lies above the plane of the ring

When O2 binds
•coordinated end-on to the Fe atom
•coordination of O2 causes the Fe(II) to switch from highspin ( t2g4 eg2) to low-spin (t2g6)
•move into the plane of the ring.
2.Hemoglobin
 Fe protein
 Found in RBC(150g/litre)
 Tetramer of myoglobin
 α2β2 tetramer
 Picks up O2 from lungs and transport it to the tissue
 Exhibit co-operativity

3.Hemerythrin
 Non-heme
 Contains 2 Fe
 Marine invertebrates
 Fe(II) binds O2
 Generally in octameric form
 Redox reaction (Fe(II) to Fe(III))
 Oxyhemerythrin-diamagnetic-spin coupling
4.Hemocyanine
 Cu protein (2 Cu)
 Non heme-No cyano group
 Mollusca & Arthropoda
 Oligomeric
 Redox reaction (Cu(I) to Cu(II))
 Deoxy form-colourless-no interaction b/w two Cu
 Oxy form-Bright blue
 Unusual dihapto manner bridging (μ-ή2ή2)
 Electron transfer proteins
1.Cytochromes
Heme proteins
Fe(III)-Fe(II) couple
Six co-ordinated
Low spin in both oxidation state
Ex:Cytochrome c oxidase,Cytochrome P450,Cytochrome b6f

Cytochrome c oxidase
The most structurally well understood cytochrome. The heme active site is
hexa coordinated with N from a histidine residue and S from a methionine
residue. Present in photosynthesis and respiration chains S(Cys) Protein

one of the oldest chemicals present in biological processes

protein S(Cys) Protein

N N
N N CH3
H Fe S
methionine
•Reduce O2 to H2O N N residue of
protein
•Contains two heme groups cyt.a and cyt.a3 &
two Cu atoms CuA and CuB
OH
HO O
O
2.Fe-S proteins

Small ET proteins containing FeS clusters are known as ferredoxins

[2Fe–2S]

[4Fe–4S]

[3Fe–4S]