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Detoxification (Xenobiotics)

Introduction to Detoxification (Xenobiotics)

Xenobiotics are toxic foreign compounds (strangers) entering our body :

They may be divided into:

(a) Pharmacological xenobiotics

Pharmacological xenobiotics include the drugs that we take intentionally

(b) Environmental xenobiotics

Environmental xenobiotics include food additives, food adulterants and pollutants present in food, water and air

  • It’s no secret
    • Pollution and pollutants are a serious problem.
    • Pollution and its effects can be found in virtually every place on earth.

Xenobiotic Exposure

  • Since WW-II between 75,000 to 80,000 new synthetic chemicals have been released into the environment: less than half have been tested for potential toxicity to adult humans.
  • Over 2 billion kgs of pesticides are used annually. This amounts to 1 kgs for every man, woman, and child.

(EPA’s Office of Prevention, Pesticides, and Toxic Substances)

Exotoxins

  • Industrial Compounds & Chemical Byproducts :-
    • Volatile Organics – Solvents & Detergents
    • Toxic Metals
    • Plasticizers
    • Insulators & Asbestos
  • Combustion / Incineration Pollutants
    • Pesticides
    • Insecticides
    • Herbicides
  • Food Additives & Preparation Byproducts
    • Cosmetic Additives
    • Synthetic Medications

Carcinogen Releases

  • Dichloromethane
  • Styrene
  • Chloroform
  • Formaldehyde
  • Tetrachloroethylene
  • Benzene
  • Acetaldehyde
  • Lead
  • 1,3-Butadiene
  • Nickel Compounds

Typical Air Pollutants

  • Carbon Monoxide
  • Ozone Formaldehyde
  • Sulfur Dioxide
  • Acetylene
  • Nitrogen Dioxide
  • Ammonia
  • Methyl Chloride

But some of it we can’t see…

  • Invisible CFC’s from aerosol sprays makes holes in the protective ozone layer.
  • Invisible fumes from chemicals used in paints, cleaners, solvents and fuels may contribute to health problems in some people.

Chemicals Frequently Detected in Water

  • Toluene
  • Trichloroethylene
  • Chloroform
  • Chlorine
  • PCB’s
  • Lead
  • Mercury
  • Pesticides
  • Chlorobenzene
  • Tetrachloroethylene

Air Pollution

  • Cigarettes, excessive alcohol, even poor diet add their weight to the toxic burden we already carry.
  • These are lifestyle choices we make for ourselves, and can thus exercise control over.

Harmful Habits

  • Our system may become overwhelmed by overexposure to the toxins found in air, water supplies as well as the chemicals and hormones added to food.
  • The symptoms of fatigue, frequent headaches, lack of mental clarity, etc. that many people feel may be the result.
  • These substances (toxins) may cause changes in our body functions
  • Pollutants and their effects have been linked to various medical problems, ranging from increased respiratory problems like asthma, and to increased risk to a variety of cancers.

Symptoms of a Toxic Body

  • Gas
  • Acne
  • Fatigue
  • Constipation
  • Cancer
  • Poor Skin
  • Difficult Breathing
  • Infertility
  • Arthritis
  • Dizziness
  • Hyperactivity
  • Allergies
  • Pre-Mature Aging
  • Obesity
  • Depression
  • Asthma
  • Insomnia
  • Aches & Pains

WHAT IS DETOXICATION

  • Detoxication means all the biochemical processes, whereby noxious substances are rendered less harmful and are more easily excreted in urine
  • The term detoxication covers all the biochemical changes proceeding in the body, which convert foreign molecules, generally toxic, to non toxic or less toxic, and more soluble so that they can be easily excreted
  • The liver is the organ primarily responsible for modifying these toxins so they can be eliminated from the body.
  • It occurs in a two-step process, called “Phase I” and “Phase II”.

Xenobiotics

Toxic foreign molecules which enter the body are called as Xenobiotics. For eg. drugs, food additives, pollutants etc.

Detoxication

Biochemical process by which toxic / noxious substances are rendered less harmful & are more easily excreted in urine.

Theory of Sherwin

  • It explains that by detoxication, toxic compounds are transformed into less toxic & more soluble derivatives, which are easily excreted.

Theory of Berczeller

  • It explains that toxic compounds are made less toxic by transforming into compounds having surface tension near to water.
  • In this way, toxic compounds are prevented from accumulation & easily excreted.

Theory of Quick

  • It explains that weak acidic substances are converted to strong acidic substances.
  • Kidney can excrete stronger acids their salts more easily than weaker acid.

Mechanism of detoxication

These are of 4 types- Oxidation,

  • Reduction, Hydrolysis and Conjugation.
  • These processes may occur independently as well as in combination inside human body. In human, detoxication is carried out in liver, but upto some extent in kidney also.
  • Detoxication process occurs in 2 phases

Phase 1

  • In this phase, main reaction is hydroxylation catalysed by monooxygenase or cytochrome P450.
  • This phase also include oxidation and reduction reactions.

CYTOCHROME P450 SYSTEM: MONO OXYGENASES

  • It is an inducible enzyme present in endoplasmic reticulum & microsomal fraction of liver (high conc.)
  • Six types of Cyt-P450 in endoplasmic 450 reticulum have been identified & described
  • Chemically, they are haemoprotein. Enzyme is NADPH Cyt-P450 reductase, which requires NADPH for its optimum activity. Cyt-P450 system contains lipids, mainly phosphatidyl choline (Lecithin)
  • Oxygenases catalyze oxidative reactions in which oxygen atoms are directly incorporated into the substrate molecule, forming a new hydroxyl or carboxyl group.
  • Monooxygenases catalyze reactions in which only one of the two oxygen atoms of O2 is incorporated into the organic substrate, the other being reduced to H2O.
  • Monooxygenases require two substrates to serve as reductants of the two oxygen atoms of O2. The main substrate accepts one of the two oxygen atoms, and a co-substrate furnishes hydrogen atoms to reduce the other oxygen atom to H2O.
  • RH + BH2 + O2 R-OH + B + H2O
  • The most common monooxygenation reactions are those employing cytochrome P450.
  • Cytochrome P450 can react with O2 and bind carbon monoxide.
  • Because the carbon monoxide complex form absorbs light strongly at 450nm — thus the name P450.
  • Cytochrome P450 catalyzes hydroxylation reactions

Hydroxylation of xenobiotics makes them more soluble in water and allows their excretion in the urine.

Other Biochemistry Notes

Biochemistry of Proteins

Carbohydrate Metabolism

VITAMIN PYRIDOXINE AND BIOTIN

Vitamin A

Pyrimidine metabolism

Purine Metabolism

Cardiac Biomarkers

VITAMIN D

. Blood Metabolism (Heme synthesis and breakdown)

Haemoglobinopathies

DNA Repair

Regulation of gene expression

DNA Replication

Transcription

Protein synthesis and genetic code

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