degradation of xenobiotics
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Transcript of degradation of xenobiotics
XENOBIOTICS
Guided By:Dr.K.S.ChandrashekharaiahAssociate ProfessorDept. of Biochemistry
Seminarian:Ganesh Prasad D.N.ll M.Sc. Biochemistry
INTRODUCTION
Xenobiotics are chemicals not naturallybelonging to or originating from a particularorganism or an ecosystem.
The term Xenobiotic derived from the GK word “Xenos=Foreigner or Stranger”
The body removes xenobiotics by xenobiotic metabolism. This consists of the deactivation and the excretion of xenobiotics and it happens mostly in the liver.
Xenobiotics • Food additives, poisons, toxins, certain drugs,
chemicals, environmental pollutants, pesticides and other foreign substances.
Xenobiotics
Xenobiotics can be-
a) Exogenous - The foreign molecules which are not
normally ingested or utilized by the organism but they
gain entry through dietary food stuffs, or in the form of
certain medicines/ drugs used for a therapeutic cause
or are inhaled through environment .
Examples- Drugs, food additives, pollutants,
insecticides, chemical carcinogens etc.
Xenobiotics can be-
b) Endogenous – Though they are not foreign substances
but have effects similar to exogenous xenobiotics. These
are synthesized in the body or are produced as
metabolites of various processes in the body.
Examples-Bilirubin, Bile acids, Steroids, Eicosanoids and
certain fatty acids.
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Source of xenobiotic compounds
1. Petrochemical industry : oil/gas industry, refineries, and the production of basic chemicals e.g. vinyl chloride and benzene2. Plastic industry :
- closely related to the petrochemical industry- uses a number of complex organic compounds such as anti-oxidants, plasticizers, cross-linking agents
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3. Pesticide industry : most commonly found central
structures are benzene and benzene derivatives,
often chlorinated and often heterocyclic
4. Paint industry : major ingredient are solvents,
xylene, toluene, methyl ethyl ketone, methyl
isobutyl ketone and preservatives
5. Others : Electronic industry, Textile industry, Pulp
and Paper industry, Cosmetics and Pharmaceutical
industry, Wood preservation
Effects of Xenobiotics
Food Chain Effects Bioaccumulation
• Primary producers and lower trophic level organisms take up PCBs, accumulates in the food chain
• Higher organisms eating primary producers get more concentrated amounts of toxin
Often people consuming higher organisms are exposed to more toxic forms than factory workers
Human Health
• carcinogenous: – Liver cancer – melanoma
• immune system– suppressed – swollen thymus gland
in infants
• reproductive system – reduced birth weight– decrease in gestational
ages– Abortions
Human Health Cont.
• nervous system– infant neurological
functions– short-term memory– Learning
• endocrine system– thyroid health
• other health effects
Marine and Animal Health• Inhibits plankton growth
and photosynthesis affecting the food chain– reduce trophic pathways
• Reduce plankton size• Reduce size of higher
feeders• Divert carbon flow to non-
harvestable species– less plankton = less bigger
food fish
• Toxic to crustaceans, mollusks, and fish at concentrations of only a few ppb
DETOXIFICATION OF XENOBIOTICS
Phases of Detoxification Processes
Phase I Phase II
DETOXIFICATION OF XENOBIOTICS
DETOXIFICATION OF XENOBIOTICS
Oxidation AlcoholAldehydes
AminesDrugs
Ethanol → Acetic acid
Methanol → Formic acid
Benzaldehyde → Benzoic acid
Aliphatic amine → Aliphatic acid + Urea
DETOXIFICATION OF XENOBIOTICS
Oxidation
Most of the oxidation reactions are catalysed by monooxygenase or cytochrom P450
Many reactions of cytochrome P450 involve
the addition of a hydroxyl group to xenobiotics
Hydroxylation
DETOXIFICATION OF XENOBIOTICS
HydroxylationThe
responsible enzymes are
called monooxygen
asesor
cytochrome P450
DETOXIFICATION OF XENOBIOTICS
Cytochrome P450
DETOXIFICATION OF XENOBIOTICS
Hydroxylation
DETOXIFICATION OF XENOBIOTICS
Reduction
It is less common and less important than oxidation.
DETOXIFICATION OF XENOBIOTICS
Hydrolysis Many drugs are detoxified by hydrolysis.
DETOXIFICATION OF XENOBIOTICS
Conjugation Glucuronic acid
Glutathione Sulfate Glycine
Conjugation means the chemical combination of one
compound with another compound.
DETOXIFICATION OF XENOBIOTICS
Conjugation with Glucuronic acid
DETOXIFICATION OF XENOBIOTICS
Conjugation with Glucuronic acid
Benzoic acid + UDP-Glucuronic acid → Benzoyl glucuronide + UDP
Paracetamol + UDP-Glucuronic acid → Conjugated product + UDP
Diclofenac sodium + UDP-Glucuronic acid → Conjugated product + UDP
DETOXIFICATION OF XENOBIOTICS
Conjugation with Glycine
DETOXIFICATION OF XENOBIOTICS
Conjugation with Glutathione
DETOXIFICATION OF XENOBIOTICS
Conjugation with sulfate
Biodegradation of Petroleum compounds
Petroleum compounds are categorized into 2 groups• Aliphatic hydrocarbon e.g. alkane, alcohol,
aldehyde • Aromatic hydrocarbon e.g. benzene, phenol,
toluene, catechol
• H.C. (substrate) + O2 H.C.-OH + H2O
• H.C. (substrate) + O2 H.C.29
OHOH
monooxygenase
dioxygenase
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Compound Organisms
Naphthalene Acinetobacter calcoaceticus , Alcaligenes denitrificans,Mycobacterium sp. , Pseudomonas sp., Pseudomonas putida , Pseudomonas fluorescens , Pseudomonas paucimobilis , Pseudomonas vesicularis , Pseudomonas cepacia , Pseudomonas testosteroni , Rhodococcus sp. , Corynebacterium renale , Moraxella sp., Bacillus cereus , Streptomyces sp.
Acenaphthene Beijerinckia sp., Pseudomonas putida, Pseudomonas fluorescens, Pseudomonas cepacia
Bacterial strain degrading PAHs
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Compound Organisms
Anthracene Beijerinckia sp., Mycobacterium sp., Pseudomonas putida, Pseudomonas fluorescens, Pseudomonas paucimobilis, Pseudomonas cepacia, Rhodococcus sp., Flavobacterium sp, Arthrobacter sp.
Phenanthrene Aeromonas sp., Alcaligenes denitrificans , Arthrobacter polychromogenes , Beijerinckia sp. , Mycobacterium sp. , Micrococcus sp., Vibrio sp., Pseudomonas putida, Pseudomonas paucimobilis, Rhodococcus sp., Nocardia sp., Flavobacterium sp., Streptomyces griseus, Acinetobacter sp.
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Compound OrganismsFluoranthene Alcaligenes denitrificans , Mycobacterium sp. ,
Pseudomonas putida , Pseudomonas paucimobilis, Pseudomonas cepacia , Rhodococcus sp.
Pyrene Alcaligenes denitrificans , Mycobacterium sp. , Rhodococcus sp.
Chrysene Rhodococcus sp.
Benz [a] anthracene Alcaligenes denitrificans , Beijerinckia sp. , Pseudomonas putida
Benz [a] pyrene Beijerinckia sp., Mycobacterium sp.
POLYCHLORINATED BIPHENYLS (PCBS)
• Synthesized chemicals from petro-chemical industry used as lubricants and insulators in heavy industry
• Used because– Low reactivity– Non-flammable– High electrical resistance– Stable when exposed to heat and pressure
Fungal Degradation
• Aspergillus niger: fillamentous with cytochrome p450 that attacks lower chlorinated PCB’s
• Phanerochaete chrysosporium: White rot fungi can attack even highly chlorinated PCB’s at low conc. (less than 500ppb) while aerobic degradation is occuring at a level of 10ppm.
Some m.o. involved in the biodegradation of xenobiotics
ORGANIC POLLUTANTS ORGANISMS
Phenolic - Achromobacter, Alcaligenes,
compound Acinetobacter, Arthrobacter,
Azotobacter, Flavobacterium,
Pseudomonas putida
- Candida tropicalis
Trichosporon cutaneoum
- Aspergillus, Penicillium
Benzoate & related Arthrobacter, Bacillus spp., compound Micrococcus, P. putida
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Organic Pollutants Organisms
Hydrocarbon E. coli, P. putida, P. Aeruginosa, Candida
Surfactants Alcaligenes, Achromobacter,
Bacillus, Flavobacterium,
Pseudomonas, Candida
Pesticides P. Aeruginosa DDT B. sphaericus Linurin
Arthrobacter, P. cepacia 2,4-D
P. cepacia 2,4,5-T Pseudomonas spp., E. coli, Parathion
P. aeruginosa
SUMMARY Xenobiotics are chemical compounds foreign to the body, such as drugs, food additives, and environmental pollutants Xenobiotics are metabolized in two phases. The major reaction of phase 1 is hydroxylation catalyzed by a variety of monooxygenases, also known as the cytochrome P450s. In phase 2, the hydroxylated species are conjugated with a variety of hydrophilic compounds such as glucuronic acid, sulfate, or glutathione. The combined operation of these two phases renders lipophilic compounds into water-soluble compounds that can be eliminated from the body. Xenobiotics can produce a variety of biologic effects, including pharmacologic responses, toxicity, immunologic reactions, and cancer.
REFERENCES• Casarett and Doull’s Toxicology, The Basic Sciences of Poisons, 5th Edition, Klassen, Amdur & Doull
(eds), Macmillan Publishing Co.• CDER Guidance for Industry: Drug Metabolism/Drug Interaction Studies in the Drug Development
Process: Studies in Vitro, April 1997, CLIN 3• Davit B, Reynolds K, Yuan R et al. FDA evaluations using in vitro metabolism to predict and interpret in
vivo metabolic drug-drug interactions: impact on labeling. J Clin Pharmacol 1999 Sep;39(9):899-910• Mansuy D (2013). "Metabolism of xenobiotics: beneficial and adverse effects". Biol Aujourdhui. 1
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