BIOCHEMISTRY - Institut Teknologi Bandungkuliah.ftsl.itb.ac.id/wp-content/uploads/2016/10/BIOCHEMISTRY.pdf · What is Biochemistry? ... • Fatty acids are components of several lipid

BIOCHEMISTRY

What is Biochemistry?

•  Biochemistry = chemistry of life.

•  Biochemists use physical and chemical principles to explain biology at the molecular level.

•  Basic principles of biochemistry are common to all living organism

How does biochemistry impact you?

•  Medicine

•  Agriculture

•  Industrial applications

•  Environmental applications

Principle Areas of Biochemistry

•  Structure and function of biological macromolecules

•  Metabolism – anabolic and catabolic processes.

•  Molecular Genetics – How life is replicated. Regulation of protein synthesis

Principles of Biochemistry    •  Cells (basic structural units of living organisms) are highly

organized and constant source of energy is required to maintain the ordered state.

•  Living processes contain thousands of chemical pathways. Precise regulation and integration of these pathways are required to maintain life

•  Certain important pathways e.g. Glycolysis is found in almost all organisms.

•  All organisms use the same type of molecules: carbohydrates, proteins, lipids & nucleic acids.

•  Instructions for growth, reproduction and developments for each organism is encoded in their DNA    

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Cells •  Basic building blocks of life •  Smallest living unit of an organism •  Grow, reproduce, use energy, adapt, respond to their

environment •  Many cannot be seen with the naked eye •  A cell may be an entire organism or it may be one of billions of

cells that make up the organism

•  Basis Types of Cells

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Nucleoid region contains the DNA •Cell membrane & cell wall • Contain ribosomes (no membrane) to make proteins in their cytoplasm

Contain 3 basic cell structures: • Nucleus • Cell Membrane • Cytoplasm with organelles

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Two  Main  Types  of    Eukaryo2c  Cells  

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Characteristic Bio-membranes and Organelles    

   Mitochondrion Surrounded by a double membrane with a series of folds called cristae. Functions in energy production through metabolism. Contains its own DNA, and is believed to have originated as a captured bacterium.

Plasma Membrane A lipid/protein/carbohydrate complex, providing a barrier and containing transport and signaling systems. Nucleus Double membrane surrounding the chromosomes and the nucleolus. Pores allow specific communication with the cytoplasm. The nucleolus is a site for synthesis of RNA making up the ribosome

Chloroplasts (plastids) Surrounded by a double membrane, containing stacked thylakoid membranes. Responsible for photosynthesis, the trapping of light energy for the synthesis of sugars. Contains DNA, and like mitochondria is believed to have originated as a captured bacterium.

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Rough endoplasmic reticulum (RER) A network of interconnected membranes forming channels within the cell. Covered with ribosomes (causing the "rough" appearance) which are in the process of synthesizing proteins for secretion or localization in membranes. Ribosomes Protein and RNA complex responsible for protein synthesis

Smooth endoplasmic reticulum (SER) A network of interconnected membranes forming channels within the cell. A site for synthesis and metabolism of lipids. Also contains enzymes for detoxifying chemicals including drugs and pesticides.

Golgi apparatus A series of stacked membranes. Vesicles (small membrane surrounded bags) carry materials from the RER to the Golgi apparatus. Vesicles move between the stacks while the proteins are "processed" to a mature form. Vesicles then carry newly formed membrane and secreted proteins to their final destinations including secretion or membrane localization. Lysosymes

A membrane bound organelle that is responsible for degrading proteins and membranes in the cell, and also helps degrade materials ingested by the cell.

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Vacuoles Membrane surrounded "bags" that contain water and storage materials in plants.      

Peroxisomes or Microbodies Produce and degrade hydrogen peroxide, a toxic compound that can be produced during metabolism.      

Cell wall Plants have a rigid cell wall in addition to their cell membranes Cytoplasm enclosed by the plasma membrane, liquid portion called cytosol and it houses the membranous organelles.

Cytoskeleton Arrays of protein filaments in the cytosol. Gives the cell its shape and provides basis for movement. E.g. microtubules and microfilaments.

http://www.biology.arizona.edu copyright © 1997 - 2004..    11

12 Biochemistry

Biolog. Nanostructures

Biochemical Evolution"

?  

CH4,  H2O,  NH3,  HCN  

How did organic complex molecules evolved from more simple molecules?  

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How did organic complex molecules evolved from more simple molecules?  

•  Urea was synthesized by heating the inorganic compound ammonium cyanate (1828)

•  This showed that compounds found exclusively in living organisms could be synthesized from common inorganic substances

The Urey-Miller experiment (1950)

Some amino acids could be produced:

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Many Important Biomolecules are Polymers

•  Biopolymers - macromolecules created by joining many smaller organic molecules (monomers)

•  Condensation reactions join monomers (H2O is removed in the process)

•  Residue - each monomer in a chain

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Molecular Organisation of a cell

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Water • About 60-90 percent of an organism is water

Water is used in most reactions in the body Water is called the universal solvent

Bio-molecules •  Just like cells are building blocks of tissues likewise molecules are

building blocks of cells.

•  Animal and plant cells contain approximately 10, 000 kinds of molecules (bio-molecules)

•  Water constitutes 50-95% of cells content by weight.

•  Ions like Na+, K+ and Ca+ may account for another 1%

•  Almost all other kinds of bio-molecules are organic (C, H, N, O, P, S)

•  Infinite variety of molecules contain C.

•  Most bio-molecules considered to be derived from hydrocarbons.

•  The chemical properties of organic bio-molecules are determined by their functional groups. Most bio-molecules have more than one.

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Biomolecules – Structure

•   Building block •  Simple sugar •  Amino acid •  Nucleotide •  Fatty acid

•   Macromolecule •  Polysaccharide •  Protein (peptide) •  RNA or DNA •  Lipid

Anabolic  

Catabolic  

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Linking Monomers Cells link monomers by a process

called dehydration synthesis (removing a molecule of water)

This process joins two sugar monomers to make a double sugar

Remove H

Remove OH

H2O  Forms  

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Breaking Down Polymers •  Cells break down

macromolecules by a process called hydrolysis (adding a molecule of water)

Water added to split a double sugar

Sugars

•  Carbohydrates most abundant organic molecule found in nature.

•  Initially synthesized in plants from a complex series of reactions involving photosynthesis. •  Basic unit is monosaccharides. •  Monosaccharides can form larger molecules e.g.

glycogen, plant starch or cellulose. Functions •  Store energy in the form of starch (photosynthesis in

plants) or glycogen (in animals and humans). •  Provide energy through metabolism pathways and cycles. •  Supply carbon for synthesis of other compounds. •  Form structural components in cells and tissues. •  Intercellular communications

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Monosaccharides -Polysaccharides

Glycosidic bonds connecting glucose residues are in red

Glucose - Cellulose

Fatty acids - Lipids

•  Are monocarboxylic acid contains even number C atoms

•  Two types: saturated (C-C sb) and unsaturated (C-C db)

•  Fatty acids are components of several lipid molecules.

•  E,g. of lipids are triacylglycerol, steriods (cholestrol, sex hormones), fat soluble vitamins.

Functions •  Storage of energy in the form of fat •  Membrane structures •  Insulation (thermal blanket) •  Synthesis of hormones

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Triglyceride

Glycerol   Fa8y  Acid  Chains  

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Structure of a biological membrane

• A  lipid  bilayer  with  associated  proteins    

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Steroids

• The carbon skeleton of steroids is bent to form 4 fused rings

Cholesterol is the “base steroid” from which your body produces other steroids Estrogen & testosterone are also steroids

Cholesterol  

Testosterone  Estrogen  

Synthetic Anabolic Steroids are variants of testosterone

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Nucleic Acids

• Store hereditary information

Contain information for making all the body’s proteins

Two types exist --- DNA & RNA

Amino acids - Proteins:  

•  Amino acids: •  Building blocks of proteins.

•  R Group (side chains) determines the chemical properties of each amino acids.

•  Also determines how the protein folds and its biological function.

•  Functions as transport proteins, structural

proteins, enzymes, antibodies, cell receptors.

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Proteins as Enzymes

•  Many proteins act as biological catalysts or enzymes

Thousands of different enzymes exist in the body

Enzymes control the rate of chemical reactions by weakening bonds, thus lowering the amount of activation energy needed for the reaction -> Catalysator

-> No not interfere with the equilibrium of reaction

-> Enzymes are reusable !!!!

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Enzymes:

•  Active site - a cleft or groove in an enzyme that binds the substrates of a reaction

Egg white lysozyme

The nature and arrangement of amino acids in the active site make it specific for only one type of substrate. (accepts just one enaniomer)

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Macromolecules

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Macromolecules

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Concepts of Life

Life is characterized by

•   Biological diversity: lichen, microbes, jellyfish, sequoias, hummingbirds, manta rays, gila monsters, & you

•  Chemical unity: living systems (on earth)

obey the rules of physical and organic chemistry – there are no new principles

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Life needs 3 things:    

(1) ENERGY, which it must know how to:  

•   Extract •  Transform •  Utilize

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The Energetics of Life

• Photosynthetic organisms capture sunlight energy and use it to synthesize organic compounds

• Organic compounds provide energy for all organisms

Using toxic O2 to generate energy

2 H2O à O2 + 4e- + 4H+ (photosynthesis)  

Glucose + 6O2 à 6CO2 + 6H2O + Energy

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Glycolysis: the preferred way for the formation of ATP

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Life needs (2) SIMPLE MOLECULES, which it must know how to:

 •   Convert •  Polymerize •  Degrade  

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Life needs (3) CHEMICAL MECHANISMS, to:

 •   Harness energy •  Drive sequential chemical reactions •  Synthesize & degrade macromolecules •  Maintain a dynamic steady state •  Self-assemble complex structures •  Replicate accurately & efficiently •  Maintain biochemical “order” vs outside

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Trick #1: Life uses chemical coupling to drive otherwise unfavorable reactions

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Trick #2: Life uses enzymes to speed up otherwise slow reactions

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How does an enzyme do it, thermodynamically?

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How does an enzyme do it, mechanistically?

Chemical reaction types encountered in biochemical processes

1.  Nucleophilic Substitution •  One atom of group substituted for another

2. Elimination Reactions •  Double bond is formed when atoms in a molecule is removed

3. Addition Reactions: •  Two molecules combine to form a single product. •  A. Hydration Reactions •  Water added to alkene > alcohol (common addition pathway)

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4. Isomerization Reactions. •  Involve intramolecular shift of atoms or groups

5. Oxidation-Reduction (redox) Reactions •  Occur when there is a transfer of e- from a donor to

an electron acceptor

6. Hydrolysis reactions •  Cleavage of double bond by water.

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Biochemical Reactions    •  Metabolism: total sum of the chemical reaction happening in a

living organism (highly coordinated and purposeful activity) a.  Anabolism- energy requiring biosynthetic pathways b.  Catabolism- degradation of fuel molecules and the production of

energy for cellular function

•  All reactions are catalyzed by enzymes

•  The primary functions of metabolism are: a. acquisition & utilization of energy b. Synthesis of molecules needed for cell structure and functioning (i.e. proteins, nucleic acids, lipids, & CHO c. Removal of waste products

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Even though thousands of pathways sound very large and complex in a tiny cell:

•  The types of pathways are small

•  Mechanisms of biochemical pathways are simple

•  Reactions of central importance (for energy production & synthesis and degradation of major cell components) are relatively few in number

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Energy for Cells    

•  Living cells are inherently unstable.

•  Constant flow of energy prevents them from becoming disorganized.

•  Cells obtains energy mainly by the oxidation of bio-molecules (e- transferred from 1 molecule to another and in doing so they lose energy)

•  This energy captured by cells & used to maintain highly organized cellular structure and functions

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ENVIRONMENTAL  BIOCHEMISTRY  

METABOLIC  RESPONCES  TO  THE  ENVIRONMENTAL  FACTORS  AND  THE  LIMITS  OF  CHANGES  THERE  OF,LEADING  TO  ADAPTATION.  

EFFECTS  OF  VARIATION  IN  ATMOSPHERIC  TEMPERATURE  &  CHEMICAL  STRESS  IN  FORM  OF  AIR,  WATER  AND  FOOD  POLLUTION.  

ALTERATION  IN  ATMOSPHERIC  TEMPERATURE  

EXPOSURE  TO  COLD  STRESS  

TYPES  OF  INJURY:  LOCAL(FROSTBITE)  &  GENERAL(HYPOTHERMIA)  

COMPENSATORY  MECHANISM  

1.   SHIVERING  PHASE  (INVOLVEMENT  OF  SKELETAL  MUSCLE)  

2.   NON  SHIVERING  PHASE  (NON  SHIVERING  THERMOGENESIS  OR  CHEMICAL  THERMOGENESIS)  

                       ~NUTRITIONAL  MODIFICATION  

                                               INCREASED  COMBUSTION,RISE  IN  TYROSINE  TRANSAMINASE  &  TRYPTOPHANPYRROLASE  ALSO  INCREASE  IN  ARGINASE.  

                       ~LIPID  METABOLISM  

                                               DECREASE  IN  TOTAL  FFA,ROLE  OF  BROWN  ADIPOSE  TISSUE  

                       ~CALORIGENIC  SHUNT  

                                               INCREASED  GLYCOLYSIS,GLUCONEOGENESIS,ROLE  OF  ETC.  

                           ~HORMONAL  EFFECT  

                                               ROLE  OF  THYROID  HOMONE  

EXPOSURE  TO  HEAT  

HEAT  BALANCE  &  HEAT  STRESS  (MUST  BE  DISSIPATED)  

VARIOUS  FACTOR  EFFECTING  IT.  

EFFECTS  OF  HEAT  STRESS  

     ~HEAT  STROKE  

     ~HEAT  HYPERPYREXIA  

     ~HEAT  EXHAUSTION  

     ~HEAT  SYNCOPE  

CHEMICAL  STRESS  AND  POLLUTION  

AIR  POLLUTION    

1.POLLUTANTS  &  CONTAMINANTS  

2.SOURCE  

                     INDUSTRIAL  

                     COMBUSTION  

                     MOTOR  VEHICLE  

                   MISCELLANEOUS  

3.INDICATORS  

                     SULPHURDIOXIDE  

                     SMOKE  INDEX  

                     SUSPENDED  PARTICLES  

HEALTH  EFFECTS  OF  AIR  POLLUTION  

1.  OXIDES  OF  SULPHUR                      INJURY  TO  RESPIRATORY  SYSTEM  

                     DAMAGE  TO  LUNG  TISSUE  

2.  OXIDES  OF  CARBON  

                   CO2  ADAPTATION:CHANGE  IN  ACID  BASE  EQUILIBRIUM  

                     CO  TOXICITY:  HYPOXIA,REACTION  WITH  Hb.  

3.  PHOTOCHEMICAL  OXIDANTS  

                       SECONDARY  PRODUCTS  OF  NITROGEN  OXIDE  

                       EYE  AND  LUNG  IRRITATION  ,  ASTHMA      

4.  PARTICULATES  

                         PULMONARY  ABNORMALITIES    

                                           SIDEROSIS(IRON)                            ASBESTOSIS(ASBESTOS)  

                                           ANTHRACOSIS(SOOT)            BYSSINOSIS(COTTON  DUST)  

                                           SILICOSIS(SILICA)                          BAGASSOSIS(SUGARCANE,RICE)  

OTHER  EFFECTS  OF  AIR  POLLUTION  

WATER  POLLUTION  

1.ORGANIC  POLLUTANTS  

                                   a.  SEWAGE,WASTE  FROM  TANNRIES,PAPER  MILLS,  FOOD  

                                               PROSSESING  INDUSTRIES.                                                                                                                                                                                                                                      

                                               DECREASE  DISSOLVED  OXYGEN  

                                               PATHOGENIC  MICROORGANISM  ,  EUTROFICATION  

                                   b.  SYNTHETIC  ORGANIC  CHEMICALS  

                                                 (  PLASTIC,PAINTS,PHARMA  WASTE)  

                                   c.  PESTICIDES  

                                                             CLASSIFICATION  

                                                                       ~CHLORINATED  HYDROCARBON  

                                                                                       (DDT,ALDRIN,DIELDRIN)  ENTERS  FOOD  CHAIN  

                                                                       ~CHLOROPHENOXY  ACID  

                                                                                         (ATRAZINE  2,4-­‐D)  

                                                                       ~ORGANOPHOSPHORUS      

                                                                                               (  MALATHIONE,DIAZINONE)  NEUROTOXIC,INHIBITOR  

                                                                                                     OF  CHOLINESTERASE    .                                

2.INORGANIC  POLLUTANTS  

HEAVY  METAL  POLLUTANTS  

             ~ENTER  INTO  FOOD  CHAIN  

               ~AFFINITY  FOR  SULPHUR;ATTACK  SULPHUR  BONDS  IN  ENZYMES  

               ~OTHER  VULNARABLE  SITES  ARE  COOH  OF  PROTEIN  ALSO  BIND  TO  CELL    

                           MEMBRANE.  

         A.  ORGANIC  MERCURIAL:  INCECTISIDES  &  BACTERICIDES,  NEUROLOGICAL    

                                                                                                   DISORDERS  

         B.  CADMIUM:  UNCOUPLER  OF  OXIDATIVE  PHOSPHORYLATION  

         C.  BERYLLIUM  :PHOSPHATE  INHIBITOR  

         D.STRONTIUM  :COMPETITOR  FOR  CALCIUM  IN  BONE  

E.  LEAD  

         ~GUIDELINES  ON  PREVENTING  LEAD  POISONING  BY  US  CDC.  

         ~ANY  CHILDREN  UNDER  6  YEARS  OF  AGE  WITH  BLOOD  LEAD  

                 LEVEL    <10  μg/dl    

       ~IN  ADULTS  ITS  <  60  μg/dl    

       ~SOURCE    -­‐-­‐  UBIQUITOUS  IN  ENVIRONMENT  (PAINTS  &  TETRAETHYL    

                                                                                                                                                                           LEAD)  

         ~CLINICAL  FEATURES  

                               IN  CHILDREN  IS  MENTAL  RETARDATION,SLOW  LEARNING,  

                                       BEHAVIOURAL  CHANGES,  LOSS  OF  4-­‐5  IQ  POINTS  FOR  EACH    

                                     10  μg/dl    OF  BLOOD  LEAD  

                                     IN  ADULTS  MENIFESTATIONS  ARE  NEUROPATHY  

                                                 ENCEPHALOPATHY  ,  ABDOMINAL  PAIN  &  SEVERE  ANEMIA.  

         ~LEAD  INHIBIT  

                                 ALA-­‐SYNTHASE,  ALA  DEHYDRATASE,  FERRO  CHELATASE  

F.  ARSENIC  

       SOURCE  :  FRUIT  SPRAYS  ,  RAT  POISON  ,  PESTICIDES  ETC.  

       TOXIC  EFFECTS:  DIZZINESS  CHILLS  CRAMPS  &  PARALYSIS  

                                   INHIBIT  SH  ENZYME  INTERFERES  WITH  CELLULAR  METABOLISM  

                                                       ALSO  CAUSES  INTRAVASCULAR  HEMOLYSIS.  

OTHER  CHEMICALS  

~FLOURINE              ~UV  RADIATION            ~RADIOACTIVE  MATERIAL  

~CFC’s  AND  HALONS  

FOOD  POLLUTION  

   I.  PROCESSING  OF  FOOD  

•  PRE  PACKAGING  -­‐-­‐  CONTAMINATION  BY  salmonella  &  staphylococcus  aureus.  

•  PACKING  –  BOTULISM  

•  FOOD  ADDITIVES  –  ANILINE  ,  CYLAMATE  ,  MONOSODIUM  GLUTAMATE  

   II.  NATURAL  TOXIN  

•  LATHYRISM—NEUROTOXIN  PRODUCE  BY  Lathyrus  sa*vum    

•  FAVISM—IN  G6PD  DEFICIENT  INDIVIDUALS  

•  ALKALOIDS—MUSCARINE  IN  MUSHROOMS  

•  GOITROGENS—THIOOXAZOLIDON  DERIVATIVES  (CABBAGE,TURNIP)  

                                                                 THIOCYANATES  &  ISOTHIOCYANATES  (RAPESEEDS,MUSTARD)  

III.STORAGE  CONTAMINATION  

 FUNGAL  GROWTH  IN  MOIST  CONDITION  

~AFLATOXIN,ERGOTOXIN    

IV.ADULTRATION  OF  FOOD  

   ~EPIDEMIC  DROPSY  

   ~ENDEMIC  ASCITES  

SUMMARY  OF  THE  CHAPTER  

ENVIRONMENTAL  BIOCHEMISTRY  

ALTERATION  IN                                                          CHEMICAL  STRESS  &  POLLUTION  ATMOSPHERIC  TEMPERATURE                                        AIR                                              WATER                                FOOD                                                                                                          ~COLD  STRESS          ~SOURCES                                                                                              FACTORS  ~HEAT  STRESS          ~INDICATORS                                                                                            ~PROCESSING                                                                  ~HEALTH  EFFECT                                                                              ~NATURAL  TOXINS                                                                  ~OTHER  EFFECT                                                                                  ~DURING  STORAGE                                                                        ACID  RAIN                                                                                                    ~ADULTERATION                                                                        GREENHOUSE  EFFECT                                                                        GLOBAL  WARMING                                                                                                                                                                                                                                                                                                                ~SOURCE                                                                                                                                                      ~ORGANIC                                                                                                                                                      ~INORGANIC                                                                                                                                                                      HEAVY  METAL(LEAD,ARSENIC)                                                                                                                                                      ~OTHERS