chemical translocation & molecular fate

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CHEMICAL TRANSLOCATION & MOLECULAR FATE Presented by - Sumer Pankaj Class – M.Sc. EST Roll no. - 42 Institute of Science and Technology for Advanced Studies and Research Affiliated to Sardar Patel University Recognized under section 2(f) and 12 (B) of UGC act 1956 Mota Bazaar, Vallabh Vidyanagar, Anand, Gujarat 38812058 PG Department of Environmental Science and Technology Veggie my 06/28/2022 Chemical translocation & Molecular Fate 1

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Page 1: Chemical  translocation & molecular fate

05/03/2023 Chemical translocation & Molecular Fate

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CHEMICAL TRANSLOCATION & MOLECULAR FATE

Presented by - Sumer PankajClass – M.Sc. EST

Roll no. - 42

Institute of Science and Technology for Advanced Studies and ResearchAffiliated to Sardar Patel University Recognized under section 2(f) and 12

(B) of UGC act 1956 Mota Bazaar, Vallabh Vidyanagar, Anand, Gujarat 38812058

PG Department of Environmental Science and Technology

Veggiemy

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Chemical translocation & Molecular Fate

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Cont

ent • Background

• Mode of action• What is translocation• Passive diffusion through cell membrane• Filtration through membrane pores• Carrier mediated transport• Engulfing by the cell• Translocation in plants (pathways)• Molecular fate/Bio-transformation of toxicants• Why bio transformation is necessary• Sites and enzymes involved in bio-transformation• Phase reactions of bio-transformation• Case study

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Background

• In the US in 2007, about 83%of all herbicide usage, determined by weight applied, was in agriculture.

• 2,4-D, the first chemical herbicide, was discovered during the Second World War.

• A toxicant is any toxic (harmful) substance which are often used to denote substances made by humans or introduced into the environment by human activity, in contrast to toxins, which are toxicants produced naturally by a living organism.

•  Toxicants are poisonous and they can enter into the plants by the stomatal openings and by root absorption.

• In animals these toxic compounds may enter by ingestion, inhalation and dermal absorption.

Veggie

Fig. Structure of 2,4- D05/03/2023

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Mode of Action

Death/Excretion (in animals & humans)

Bio-chemical Response

Molecular Fate

Translocation

Absorption• Mode of action refers to the series of steps from the site of

application to death of the plant.• Mode of action comprises the sum total of anatomical,

physiological, and bio-chemical responses that make up the total phytotoxic action of a chemical as well as physical and molecular fate of aa chemical.

• The copper ion is the component of copper sulphate used as fungicide and herbicides. Copper ions appear to bind to functional groups of protein molecules in fungi and algae which cause protein denaturation, producing cell damage.

• In molluscs, copper sulphate disrupts surface epithelia function and peroxidase enzymes.

• Ingestion of copper sulphate irritates the digestive system, Tissue corrosion, shock and death may occur at large dosage. Damage to blood cells, liver and kidney has also been reported.

• Sheep can be particularly sensitive to products containing copper sulphate.

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What is Translocation ?• Translocation may be defined as a process which converts thee lipophilic compounds to more hydrophilic

metabolites so that it can pass through the cell membrane.

Absorption of Toxicant

• Inhalation• Ingestion• Dermal contact

Blood stream

• Depending upon the Blood flow rate to organs.

Capillary walls

Cell Membra

nes

• Made up of Lipoprotein membrane

• Through diffusion

Mechanism Of Translocation

Passive Diffusio

n through

the membra

ne

Filtration

through the

membrane pores

Carrier-mediate

d transpo

rt

Engulfing by the

cell

Fig – figure showing the translocation of a toxicant

• Chemicals like Endosulfan, once entered into the body in higher amount deposits in body (cannot be excreted) and alter the biotic metabolism

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Passive diffusion though cell membrane• Most of the toxicants enter into the cell membrane by

simple passive diffusion (no energy required).

• The toxicant moves from lower concentration area to higher concentration areas. The rate of passage is related directly to the concentration gradient across the membrane and the lipid solubility.

• NOTE :- Many toxicants are ionisable. They ionize to form ions and are unable to penetrate the cell membrane because of its low lipid solubility.

Chemicals

Mannitol

Acetylsalicylic acid

Thiopental

% absorbance

by cell membrane

<2%

21%

67%

Fig – Table showing the % absorbance of different chemicals across the cell membrane

based on their lipid solubility.

• The rate of diffusion can be calculated by dividing the product of the gradient,

temperature, surface area, solubility of the molecule by the product of the distance and

square root of the molecular mass.

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Filtration through the membrane pores

• In a biological system filtration takes place through the pores present on the membranes eg:- pores present on the glomerulus membrane.

• When the blood flows into the glomerulus of bemoans capsule the chemicals smaller than the RBC’s and WBC’s are filtered out and passed to the Proximal Convoluted tubule (PCT) and the clean blood is passed to the efferent arteriole

• Capillaries of the glomerulus are lined by endothelial cells. These contain numerous pores (50–100 nm in diameter)

• large and/or negatively charged molecules will pass through far less frequently than small and/or positively charged ones. For instance, small ions such as sodium and potassium pass freely, while larger proteins, such as haemoglobin and albumin have practically no permeability at all.

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Carrier-mediated transport

• There are certain macromolecule embedded in the cell membrane known as carrier proteins (porines) which have higher affinity to the toxic chemicals, Hence, these chemicals bind with the macromolecules present in the body and enter the cell. After entering into the cell the complex dissociates and the macromolecule again binds with another toxic molecule.

• This process depends on structure, size and ions and affinity of the chemical to carrier site.

• This means of transport is an active transport (requires energy) which takes place against the concentration gradient or electrochemical gradient.

• Facilitated diffusion is similar active transport but dose not take place against

concentration gradient.

• Poison are the substances that binds these carrier macromolecules and stops the exchange of ions and metabolites.

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Engulfing by the cell

• The solid particles and the liquid may be engulfed by the cells in two ways.

• When the particles are solid , the process is known as Phagocytosis while if they are liquid, it is called as pinocytosis.

• These process takes place for the removal of toxicants from alveoli and from the blood streams.

• Autoimmunity is the system of immune responses of an organism against its own healthy cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease.

• An autoimmune disease develops when your immune system, which defends your body against disease, decides your healthy cells are foreign. As a result, your immune system attacks healthy cells.

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Translocation in Plants • The way in which water from soil enters roots,

particularly to the root xylem, is called "mechanism of water absorption. In higher plants water is absorbed through root hairs which are in contact with soil water and form a root hair zone a little behind the root tips.

• Mechanism of water absorption is of two types:

• (1) Active Absorption of Water/Symplastic movement

• In this process the root cells play active role in the absorption of water and metabolic energy released through respi ration is consumed.

• (2) Passive Absorption of Water/apoplastic movement

• It is mainly due to transpiration, the root cells do not play active role and remain passive.

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Pathways of water passage from root hairs to xylem

• (i) Apoplast Pathway:

• Here water passes from root hair to xylem through the walls of intervening cells without crossing any membrane or cytoplasm. This pathway provides the least resistance to movement of water. However, it is interrupted by the presence of impermeable lignosuberin casparian strips in the walls of endodermal cells.

• (ii) Non-vacuolar Symplast Pathway:

• Water passes from cell to cell through their protoplasm. It does not enter cell vacuoles. The cytoplasm of the adjacent cells are connected through through bridges called plasmodesmata. For entering into symplast, water has to pass through plasma lemma (cell membrane) at-least at one place. It is also called trans-membrane pathway,

• (iii) Vacuolar Symplast Pathway:

• Here individual root cells function as tiny osmotic systems. The first osmotic system operates at root hair cell. It absorbs water from soil through osmosis. The pathway is cell wall, plasma-lemma, cytoplasm, tonoplast and central vacuole. From root hair eel, water passes into vacuoles of adjacent cortical cell through osmosis.

• The process continues till water reaches the xylem parenchyma cells. However, vacuolar pathway provides a lot of resistance. It is used only when individual cells are to pick up water. Otherwise, the usual pathway of water movement is partly apoplastic and partly symplastic.

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Molecular Fate/Bio-Transformation of Toxicants

• Biochemical alteration of chemicals such as nutrients, amino acids, toxins, and drugs in the body through certain processes like oxidation, hydrolysis, conjugation with the help of some specific enzymes. This process is also know as Bio-transformation.

• It is also needed to render nonpolar compounds polar so that they are not reabsorbed in renal tubules and are excreted.

• The body typically deals with a foreign compound (DRUGS) by making it more water-soluble, to increase the rate of its excretion through the urine.

• If there is no detoxification of the substance then the toxin or drug enters into ADR (Adverse Drug Reaction) phase which may disturb the normal functioning of the body.

• This Bio-transformation generally takes place in the body to convert lipophilic compound to more hydrophilic compounds, so that it can be easily excreted out of the body.

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Why Molecular fate is necessary ???

 (Beta amyloid (Aβ)Glutamate, oxygen radicals, Heavy metals like Pb, Hg etc.)

(Cyanide, hydrogen disulphide)

(Cyclosporin A, asbestos) 

(O-Nitrotoluene)

 (Ciprofloxacin,Ciclosporin)

(microcystins, Acetaminophen (Paracetamol), Nonsteroidal anti-inflammatory drugs, Glucocorticoids)

(Nicotine,Pollutants,Chloroform,Volatile solvents.)

(Bromobenzene,Thiobenzamide,Thioacetamid.)

Inactivation of drug

(Detoxification).

Activation of Drug (Bio-activation)

Partially active metabolites

(Valium

Proc

ess o

f Bio

-tra

nsfo

rmat

ion.

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Site and enzymes used in biotransformation

Brain

LungsSkinIntestinesLiver

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Phase I

• Includes oxidative, reductive, and hydrolytic reactions.

• In these type of reactions, a polar group is either introduced or unmasked, so the drug molecule becomes more water-soluble and can be excreted.

• Reactions are non-synthetic in nature and in general produce a more water-soluble and less active metabolites

Phase II

• These reactions involve covalent attachment of small polar endogenous molecule such as glutamic acid, sulfate, or glycine to form water-soluble compounds.

• This is also known as a conjugation reaction.• The final compounds have a larger molecular

weight.

Phases of Bio-transformation

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Phase – 1 Oxidation reaction

• Here substrate loses electrons.• There is an addition of oxygen, dehydrogenation (removal of Hydrogen), or simply

transfer of electrons from one compound to other.• Phenytoin

HydroxyphenytoinHydroxylation

(removal of H2)

• Codeine MorphineDealkylation (removal of alkyl

group)• Cimetidine Cimetidine

sulfoxideS-oxidation (addition of

sulphuroxide)• Amphetamine

BenzylmethylketoneDeamination

(removal of amine group)

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Phase 1 – Reduction reactions• Addition of hydrogen or removal of

oxygen from a drug molecule.

Here the substrate gains electrons.

Occurs when oxygen content is low.

Common reaction

- Azo reduction - Dehalogenation

- Disulfide reduction - Nitro reduction

- N-oxide reduction - Sulfoxide reduction

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Phase 1 – Hydrolysis reaction

• Process where a drug molecule is split by the addition of a molecule of water.• -OH group to one fragment and –H to other• Both microsomal and non-microsomal enzymes maybe involved.• Eg: acetylcholine+ H2O choline + acetic acid• Eg : Larger chemicals such as esters, amines, hydrazine, and carbamates

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Phase 2 – Conjugation Reactions• Phase 2 reactions include all Conjugation reactions.• In phase 2 reactions some endogenous substance is added to the reactive site of the

Phase I metabolite to make it more water-soluble.

Type – 1 • Methylation• Glucuronidati

on• Sulfation• Acetylation

Type - 2• Peptide

conjugation• Glutathione

conjugation• Glycosylation

Conjugation reactions

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Type 1 Reactions

Fig - Sulfation Fig - Acetylation Fig -GlucuronidationType 2 Reactions

Fig - Peptide conjugation Fig - Glutathione conjugation Fig - Glycosylation05/03/2023Chemical translocation & Molecular Fate

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Phase 3 Transportation Additional conjugation reaction takes place here. ABC (ATP-binding cassette transporters) family including MDR proteins -

Multidrug resistance-associated protein Conjugates and their metabolites can be excreted from cells as they are more

hydrophilic in nature now. Transpoter

s

Anionic transporter : OATP1B1/SLCO1B1 Cationic transporters :

OATP1B3/SLCO1B3ABC transporters: P

glycoprotein

Tran

spor

t M

echa

nism Importing

Exporting

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IMPORTING EXPORTING

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Case study

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References• https://en.wikipedia.org/wiki/Herbicide• http://

passel.unl.edu/pages/informationmodule.php?idinformationmodule=1057703469&topicorder=5&maxto=6

• https://passel.unl.edu/pages/informationmodule.php?idinformationmodule=1056648673• http://www.agriinfo.in/default.aspx?page=topic&superid=1&topicid=2224• https://www.ncbi.nlm.nih.gov/pubmed/11838430• https://www.ncbi.nlm.nih.gov/pubmed/20401520• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC201369/• https://en.wikipedia.org/wiki/Chemical_transformation• http://link.springer.com/protocol/10.1385%2F1-59259-409-3%3A49#page-1• https://en.wikipedia.org/wiki/Mode_of_action• http://www.dictionary.com/browse/translocation

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26THANK YOU…05/03/2023