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. 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. 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.

1. 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
2/17/2017 Chemical translocation & Molecular Fate
1

2. Content
• 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
2/17/2017Chemical translocation & Molecular Fate
2

3. 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 SecondWorld 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- D
2/17/2017
Chemical translocation & Molecular Fate
3

4. 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. 2/17/2017Chemical translocation & Molecular Fate
4

5. 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
Membranes
• Made up of
Lipoprotein
membrane
• Through
diffusion
Mechanism Of
Translocation
Passive
Diffusion
through
the
membrane
Filtration
through
the
membrane
pores
Carrier-
mediated
transport
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
2/17/2017Chemical translocation & Molecular Fate
5

6. 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.
2/17/2017
Chemical translocation & Molecular Fate
6

7. 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.
2/17/2017Chemical translocation & Molecular Fate
7

8. Carrier-mediatedtransport
• 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.
2/17/2017
Chemical translocation & Molecular Fate
8

9. 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.
2/17/2017
Chemical translocation & Molecular Fate
9

10. 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 respiration 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.
2/17/2017Chemical translocation & Molecular Fate
10

11. 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.
2/17/2017Chemical translocation & Molecular Fate
11

12. 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.
2/17/2017
Chemical translocation & Molecular Fate
12

13. 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
ProcessofBio-transformation.
2/17/2017Chemical translocation & Molecular Fate
13

14. Site and enzymes used in biotransformation
Brain
Liver
2/17/2017Chemical translocation & Molecular Fate
14

15. 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
2/17/2017Chemical translocation & Molecular Fate
15

16. 2/17/2017
Chemical translocation & Molecular Fate
16

17. 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
sulfoxide
S-oxidation (addition
of sulphuroxide)
• Amphetamine
Benzylmethylketone
Deamination (removal
of amine group)
2/17/2017Chemical translocation & Molecular Fate
17

18. 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
2/17/2017Chemical translocation & Molecular Fate
18

19. 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
2/17/2017
Chemical translocation & Molecular Fate
19

20. 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
• Glucuronidation
• Sulfation
• Acetylation
Type - 2
• Peptide
conjugation
• Glutathione
conjugation
• Glycosylation
Conjugationreactions
2/17/2017Chemical translocation & Molecular Fate
20

21. Type 1 Reactions
Fig - Sulfation Fig - Acetylation Fig -Glucuronidation
Type 2 Reactions
Fig - Peptide conjugation Fig - Glutathione conjugation Fig - Glycosylation
2/17/2017
21

22. 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.
Transpoters
Anionic transporter :
OATP1B1/SLCO1B1
Cationic
transporters :
OATP1B3/SLCO1B3
ABC transporters: P
glycoprotein
TransportMechanism
Importing
Exporting
2/17/2017Chemical translocation & Molecular Fate
22

23. IMPORTING EXPORTING
2/17/2017Chemical translocation & Molecular Fate
23

24. Case study
2/17/2017Chemical translocation & Molecular Fate
24

25. 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
2/17/2017Chemical translocation & Molecular Fate
25

26. THANK YOU…
2/17/2017Chemical translocation & Molecular Fate
26