Biochemical and Molecular Toxicology

How Passage of Chemical through Body

A toxicant can enter the body in several ways it can be through the skin’s respiratory passage digestive system.

If the skin is in contact with acid it causes an effect on the skin where it exposes this is the simplest example in the majority of cases chemical interbody and then exerts a toxic effect at a different site in the body during its distribution the body can detoxified it bye different defense mechanism, for example, it metabolizes it different chemical or removes it from the body by excretion the body defense mechanism consists of four-step

Absorption: Distribution: Metabolism: Excretion

In the first step, the toxicant is absorbed through the different passage and enters the body where it exerts it adverse effect at the point of exposure or it can be distributed to the other part of the body where it can be changed into other less toxic substances or can be excreted outside the body

Absorption:

The most common way for a toxicant to enter the body is ingestion.Inhalation.Dermal or skin absorption

For the absorption, the toxicant can enter or pass through the cell membrane to reach the plasma off the cell this technique by simple diffusion facilitative diffusion or by using energy active

transport but the most common way of transport of toxicants through plasma membrane is passive diffusion which needs only concentration gradient and nonpolar lipophilic compound This process do not need any kind of energy the cell membrane is a lipids bilayer so the lipophilic compound can easily pass through the membrane

Distribution

After reaching the plasma of the cell chemical can be transported throughout the body showing its effects in all the body but the amount of toxicant is not equal in all the body parts it depends upon the blood flow as different parts of the body receive a different quantity of blood supply.

Therefore the amount of toxic and is also different in these organs for example heart liver and lungs receive a major quantity of blood during cardiac circulation therefore or the accumulation of these

Metabolism:

Metabolism is a sum of all chemical reaction taking place in the normal body whether they are anabolic or catabolic body can also metabolize chemicals to less toxic substances to decrease its effect on the body

Excretion:

The Chemicals remove from the body true pieces are urine small molecule are excreted through Kidneys why large molecules move to liver where it pass to the feces by bile duct and excreted through the body

Biochemical Toxicology

The interaction of toxicants and organisms at the cellular level is studied in the branch of biochemical toxicology of applied biology. Study the toxic effects and their interaction are fundamental understanding these effects may be chronic or acute these concepts are very useful how to make new or techniques methodologies and therapies for the analysis of toxic effects and for the formation of new clinical drugs are antibiotics medicine or different biocides in agriculture the effect of these poisons considered as a cascade.

But in the case of Molecular toxicology and chemical toxicology involve analysis which is restricted to the use of biomarkers and their Discovery there are some Expo year which involves the biochemistry  and the distribution of cell membrane transport process taking place within the body involve the metabolism of toxicants their point of entry and their distribution in the organs such as liver where the detoxification of toxicants take place these toxicants maybe be activated or making more toxic than the parent for example in

The liver detoxification take place some Chemicals have intrinsic toxicity which reacts with metabolites for many modes of toxic action direction include the reaction of toxicants with macromolecules like DNA and protein which have high molecular weight the most important area of toxicology is the study of toxic action and their modes of action Dev action are studied at the different organization level for example at organ level cellular level or tissue level at organ level there are different fields rashes dermo toxicology days with the toxic effect of toxicants on the skin immunotoxicity the toxicity of central nervous system and peripheral nervous system is studied in the neurotoxicology and other fields are hepatoxicology respiratory toxicology

Cellular Toxicology

Tissue culture technique was known since yearly twenty century these cultures a prepared from living organism cells, with the development immunologist cell lines benefit of experimental biology and cell culture has been increased it is comparatively Les complex to study the toxic effect on a cellular level rather than studying on an intact organism level which is more complex and its potential utility for routine toxicity the liver cells have not the ability to divide and they are short-lived so they must be used in primary cell culture other cells which are capable of dividing are used another cell culture which incorporates with the tumor cells and they are the ability to divide is retained after continuous cell lines the cells has some of the features of normal cells nontumor cells cooperation study and techniques of Cell and Molecular Biology enhances the benefit for experimental toxicology as the cell can be used for genetic study reproduction and studying in enzymatic effects.

Molecular Toxicology

Buy the discovery of genetic code and the structure of DNA a double-helical by Watson and Crick model the field of Molecular Biology was started after that about 50 years that methodology and techniques of Molecular Biology have risen too many fields of biology e as it’s important to increase the study of the genome of a different organism in evolutionary tree Rises with the success of Human Genome Project genetically modified mice production PCR molecular cloning these are the techniques which have been valuable and important in toxicology analysis of risk and toxic hazards in the fields of applied biology some techniques have been valuable and potentially useful for example micro race used to evaluate gene expression under various circumstances bioinformatics stores integrate and manage a large amount of genomic data and easily accessible by the user having optimized algorithm and web interfaces

Life before Oxygen

Molecular oxygen is very important it for the organism which aerobically respires but at the same time it is toxicant for those which anaerobic in the bacterial Kingdom many groups of bacteria are killed when they are exposed to molecular oxygen and at the same time organism which respires on oxygen may I also not survive on the high concentration of oxygen because the excessive dose of everything is a toxicant.

For example, if mice are kept in a pure oxygen environment they can survive for only one week this takes place due to the Lang abnormality and damage as chronic lung disease and retinopathy molecular oxygen have an acute effect on the anaerobic organism and chronic effect on aerobic organism cells molecular oxygen cause of oxidative stress which cause many e physiological changes for example cell signaling pathological stress neurodegeneration cardiology disease diabetes about a half-century ago a scientist named Stanley Miller to prove that Wan Hai

electrical charge is passed through gases which are present in atmosphere like ammonia methane hydrogen they produce complex organic compound such an as Sugar and amino acids the reduction of these gases make possible the origin of life by the synthesis of prebiotic Chemical synthesis for example reduction of carbon mono oxide this reaction took place by the energy provided by sunlight and another geological source of energy but the evolution of molecular oxygen started by the evolution of the photosynthetic organism.

Reduction of Molecular Oxygen 4 electrons are required for the whole reduction of molecular oxygen to H20 and this has large positive redox potential Desh Redox reaction this Redox reaction is are thermodynamically favorable by almost all biochemical reactions, molecular oxygen is a paramagnetic homonuclear diatomic molecule that exists as ground state two electrons are antibonding they have the same spin due to this paramagnetic behavior molecular oxygen cannot react with diamagnetic organic molecule due to different state of spin the energy production during the reduction of molecular oxygen can be released by managing spin restriction the enzyme having metallic ions of transition group are those having univalent valency provides partially reduced intermediates.

O2 + e* —* Or (superoxide anion)

O2′ + e’ + 2H~ —* H:0: (hydrogen peroxide)

H2O2 + e’ —> OH*+ OH’ (hydroxyl radical) OH’+ e + H+ —* H2O (water)

 

Oxidation Mechanism 18-century Oxygen was discovered by Cal William and Joseph Priestley oxidation was considered as the fundamental of life the cells which do not involve oxidation died but in the 20 century it was clear that oxidation can carry out in anaerobic condition by studying a tissue in an anaerobic condition weather quantitative experimental enzymology

Detoxification of Hydrogen Peroxide

In 1888 French scientist Lois Jacques first prepares hydrogen peroxide. He examined that when organism tissue is treated with hydrogen peroxide it produces molecular oxygen and bubbles are formed. This concept was greatly used in the enzymatic study for many years

The reaction proceeds in the following way

H2O2 + H2O2 —> H2O + O2

This reaction is catalyzed by an enzyme group catalase named as Hydrogen peroxide oxidoreductase.

It was early thought that hydrogen peroxide is decomposed by enzyme universally and it is a universal property of enzyme to decompose the hydrogen peroxide.

In the eukaryotic cell, the decomposing of hydrogen peroxide take place in penalized organelles called peroxisomes. It is generally produced in the cell in two ways by the peroxisomal oxidative activities or by the dismutation of oxides which is the byproduct of respiration. Hydrogen peroxide is very reactive and can pass from the membrane of the cell easily and also easily transported between the cell’s organelles between cells and tissue by simple diffusion.

Besides its toxic properties, it also acts as a chemical messenger that activates the signal transduction cycle.

Catalases the catalyst is in the mammalian cell is a tetrameric protein the molecular mass of this protein is about 240 kilo Dalton one heme group and one molecule of nadph2 is present in each unit of this protein erythrocytes obtain their NADPH from this catalase enzyme organelle which are associated with reduction of hydrogen peroxide have this catalase enzyme this enzyme is present for example in the cytosol of erythrocytes liver and other tissues where the production of hydrogen peroxide take place enzyme has specific structure substrate specificity expression pattern and other unique characteristics, therefore, they are used a marker to detect mammalian peroxide enzyme

Reaction Cycles of Catalase and Peroxidases

By using the technique of spectrophotometer scientist named Britain chance and his colleagues in 1940 e at the University of Pennsylvania observe the decay of intermediates in the reaction of catalase and peroxidase this observation was the very first to apply Rapid Kinetic techniques on the enzymatic study of the catalyst containing ferric heme group produce short leave oxidized intermediates which chance named as compound 1 catalase similarly peroxidases also produce a similar type of compound one intermediate at the start of the cycle when these intermediates react with reduced organic substrates they returned to the resting ferric state this state is known as intermediate compound 2 state

  • Peroxidase (Fe+3) + H202 Peroxidase
  • Compound 1 (Fe+S02—) + H20 Peroxidase
  • Compound I (Fe+502—) + RH2 Peroxidase
  • Compound 11 (Fe+4) + + OH Peroxidase

Reviewed by:
Dr. Muhammad Adnan Asghar (Ph.D.)
Chinese Academy of Sciences Fuzhou, Fujian