BTE315 Lecture 11 Xenobiotics Bioremediation PDF

BTE315 Lecture 11 Xenobiotics Bioremediation Dr. Munima Haque  Xenobiotics ( Xenos = strange) are compounds that are foreign to the body. It includes drugs, food additives, pollutants etc. Understanding how xenobiotics are handled at the cellular level is important in learning how to c...

BTE315 Lecture 11 Xenobiotics Bioremediation Dr. Munima Haque  Xenobiotics ( Xenos = strange) are compounds that are foreign to the body. It includes drugs, food additives, pollutants etc. Understanding how xenobiotics are handled at the cellular level is important in learning how to cope with the chemical attack. Catabolism of xenobiotics Metabolism of xenobiotics is considered in: phase 1: involved hydroxylation, catalyzed by monooxygenases or cytochrome P450( involved by NADPH). phase 2: conjugation with glucuronic acid,sulfate, acetate, glutathione, or certain amino acids, or by methylation.  The overall purpose of the two phases is to increase their water solubility( polarity) and thus excretion from the body. Xenobiotics are prodrugs or procarcinogens. Detoxification is usually used as terms to metabolism of xenobiotics. Cytochrome P450 Hemoprotein, like hemoglobin. Widely distributed across species. Present in highest amount in liver and small intestines, mainly in the membranes of the smooth endoplasmic reticulum. Substrate specificity. NADPH is involved in reaction mechanism in cyt P450. Lipids also components of cyt P450 system. Most of cyt P450 are inducible.  Certain isoforms of cyt P450 involved in metabolism of PAH( polycyclic aromatic hydrocarbons) and called AHH( aromatic hydrocarbon hydroxylases). Certain cyt P450 exist in polymorphic forms. Conjugation reactions Glucuronidation Sulfation Conjugation with glutathione Acetylation e.g. in INH( isohydrazid) Methylation  Activities of xenobiotics metabolism affected by species, genetic factors, gender, age. Intake phenobarbital or certain hydrocarbons can cause enzyme induction.  The goal of xenobiotics metabolism is make xenobiotics less poisonous or nontoxic metabolite. Recalcitrant molecules Definition: In environment any compound or molecule that persists in nature for long time and resist degradation. Xenobiotic Compounds The term Xenobiotic means a chemical substance that is not a natural component of a living organism exposed to it, i.e. a strange, exogenous substance or anthropogenic material.  An important group of xenobiotics are chemical compounds produced by humans, with artificial chemical structure, to which organisms have not adjusted through prior evolution.  Man made chemicals, not produced naturally Present in the environment at unnaturally high concentrations Microbes have the capability to degrade all naturally occurring compounds  Microbes can degrade many of the xenobiotic compounds, but some remain non-degradable – these are called Recalcitrant compounds. Examples of recalcitrant compounds biodegraded by ligninolytic and peroxidase enzymes: lignin monomers, polycyclic aromatic hydrocarbons (PAHs), and halogenated compounds Recalcitrant Xenobiotic compounds Xenobiotics may be recalcitrant due to: 1. they are not recognized as substrates by the existing degradative enzymes 2. they are highly stable, chemically and biologically inert  3)they are insoluble in water/adsorbed to soil 4). they are highly toxic 5). their large molecular weight prevents entry into microbial cells  Types of recalcitrant Xenobiotic compounds 1. Polychlorinated biphenyls 2. Synthetic polymers 3. Alkylbenzyl sulphonates 4. Oil mixtures 5. Others like Pesticides etc.  Halocarbons - PCBs These compounds contain different number of halogens as substitutes. These are used as solvents, as propellants, sprays, cosmetics, paints in condenser units of cooling systems (Freons), Insecticides, Herbicides  Polychlorinated Biphenyls (PCBs) These compounds have two covalently linked benzene rings having halogens as substitutes. PCBs are used as plasticizers, insulator coolants.  Synthetic Polymers These are produced as plastics – polyethylene, polystyrene, polyvinyl chloride, nylon etc. These are recalcitrant due to their insolubility and high molecular weight.  Hazards of Xenobiotics Toxicity – many xenobiotics are toxic to bacteria, eukaryotes, even humans Carcinogenicity :Recalcitrant compounds accumulate in environment causing pollution. Many compounds show bioaccumulation and Biomagnification  Transformation of Xenobiotics Biodegradation mineralization or transformation  Mineralization is the complete decomposition of an organic compound into inorganic elements. Biodegradation is a process of decomposition of organic compounds into inorganic elements taking place with the participation of living organisms with the simultaneous accretion of biomass.  Biotransformation Biotransformation isthe process leading to the change of the structure of the original chemical compound to such degree that its original characteristic properties change as well.  Rate of transformation The scope and rate of all transformations of xenobiotics depends on: Chemical structure and concentration of the xenobiotic Type and number of microorganisms capable of degrading or transforming the xenobiotic The physico-chemical properties of the environment  Bioavailability of xenobiotics The bioavailability of a xenobiotic depends on its state (solid, liquid or gas) water solubility capability of adsorbing and adhering to solid particles of soil or sediment Water-dissolved fraction of the xenobiotic is available to the microorganisms.  Biodegradation of Xenobiotics General features: Since xenobiotics consist of a wide variety of compounds their degradation occurs via many metabolic pathways. Biodegradation involves conversion of complex molecules to simpler molecules or if possible to CO2 and H2O.  Aerobic metabolism : Microbes use O2 in their metabolism to degrade contaminants Anaerobic metabolism: Microbes substitute another chemical for O2 to degrade contaminants Nitrate, iron, sulfate, carbon dioxide, uranium, technicium, perchlorate.  Biodegradation of Petroleum compounds The ring structure is opened up in case of cyclic compounds. Linear molecule is degraded by β-oxidation to acetyl CoA which is further metabolized through TCA cycle.  The complete biodegradation (mineralization) of hydrocarbons produces the non-toxic end products carbon dioxide and water, as well as cell biomass (largely protein) which can be safely assimilated into the food web (Atlas, 1995).  Biodegradation of Petroleum compounds Alicyclic hydrocarbons are subsequently converted to carboxylic acids that are further biodegraded via ß-oxidation to yield acetyl CoA. Aromatic hydrocarbon rings generally are hydroxylated by Dioxygenases to form diols; the rings are then cleaved with the formation of catechols.  Catechol is further metabolized either via Ortho ring cleavage or Meta ring cleavage. Subsequently degraded to intermediates of the tricarboxylic acid cycle. Origin of Capacity to degrade Xenobiotics The continued exposure of microorganism to xenobiotics lead to evolution of partial or complete xenobiotic degradation capacities in microbes through metabolic pathways.  The molecular mechanisms involves: 1. mutation 2. transfer of genes through plasmids e.g., TOL plasmids, pAC21, pAC25. References and videos https://www.frontiersin.org/articles/10.3389/fbioe.2020.570307/full http://vikramuniv.ac.in/files/wp- content/uploads/B_Sc_Biotech_6_sem_P_3_env_By_Dr_Santosh_Thak ur.pdf https://link.springer.com/article/10.1007/s00253-004-1864-3 Videos https://www.youtube.com/watch?v=Z0ikkdNDdmI https://www.youtube.com/watch?v=xxkrr1gf2GE THANK YOU [email protected]