Skip to content
Login Register

#detoxification

6 public questions tagged with this topic.

Basics of Cell Biology

Which of the following organelles is involved in detoxification?

Detoxification of endogenous metabolites and exogenous xenobiotics requires oxidative handling and compartmentalization to protect cellular components. Peroxisomes, single membrane organelles containing enzymes imported via peroxisomal targeting signals PTS1 C-terminal SKL tripeptide and PTS2 N-terminal recognized by shuttling receptors PEX5 and PEX7, house acyl-CoA oxidases that beta-oxidize very-long-chain fatty acids C22 and above and branched-chain fatty acids like phytanic acid generating acetyl-CoA for mitochondria plus hydrogen peroxide H2O2 as byproduct. Catalase, core component with heme prosthetic group and highly abundant crystal, rapidly dismutates H2O2 to water and oxygen preventing oxidative damage to lipids and DNA; absence or peroxisome biogenesis disorders such as Zellweger syndrome cause accumulation of VLCFA and neurological defects and liver dysfunction. Additionally D-amino acid oxidase, urate oxidase in non-primate organisms, and enzymes for plasmalogen ether lipid synthesis provide antimicrobial and membrane functions. Smooth ER complements via cytochrome P450 monooxygenase family CYP3A4, CYP2D6 hydroxylating xenobiotics increasing solubility, followed by conjugation via glucuronosyltransferases. Nucleus safeguards genome, Golgi processes glycans, lysosomes degrade polymers, but oxidative detoxification is hallmark of peroxisomes together with smooth ER collaboration.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 12: Peroxisomes and Detoxification.

View Details
Membrane Transportation

The ABC transporter in plants responsible for detoxification of xenobiotics is found in:

Plants lack animal Na+/K+ gradient but generate proton motive force via plasma membrane P-type H+-ATPase and vacuolar V-type H+-ATPase and pyrophosphatase, driving uptake and compartmentalization of metabolites. Detoxification of xenobiotics, herbicides, and endogenous secondary metabolites employs ATP-binding cassette transporters localized predominantly in vacuolar membrane tonoplast and plasma membrane. Vacuolar ABCC members often called MRP-like transport glutathione S-conjugates, phytochelatin heavy metal complexes, and glucuronide conjugates into vacuole for sequestration, reducing cytosolic toxicity. Plasma membrane ABCG members extrude antimicrobial terpenoids and cuticular lipids. In Arabidopsis, AtABCC1 and AtABCC2 are classic vacuolar transporters conferring tolerance to arsenic and cadmium phytochelatin complexes. Tonoplast localization enables long-term storage away from sensitive metabolic processes, paralleling hepatic canalicular ABC exporters. Exclusive peroxisomal or endoplasmic reticulum residence is not typical for xenobiotic detoxification ABC pumps; tonoplast and plasma membrane are major detox sites contributing to environmental adaptation. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.

Ref: Martinoia et al., Planta 2002, Vacuolar transporters; Kang et al., PNAS 2011, ABC in detox.

View Details
Cell Organelles

The major function of peroxisomes is:

Peroxisomes are single membrane oxidative organelles discovered by Rhodin and De Duve, numbering hundreds per cell, containing more than fifty enzymes producing and degrading hydrogen peroxide. Beta-oxidation of very long chain fatty acids greater than twenty two carbons, branched phytanic acid alpha-oxidation, bile acid intermediate shortening and ether lipid synthesis of plasmalogens providing antioxidant membranes and myelin components occur via enzymes acyl-CoA oxidase generating H2O2, bifunctional enzyme and thiolase. Catalase converts two H2O2 to water and oxygen detoxifying, also urate oxidase and D-amino acid oxidase produce peroxide. Import depends on peroxisomal targeting signals PTS1 tripeptide SKL at C terminus recognized by Pex5 receptor and PTS2 nonapeptide recognized by Pex7. Protein degradation via lysosomal hydrolases acidic, ATP synthesis mitochondrial inner membrane, nucleic acid processing nuclear. Defects in Pex genes cause Zellweger spectrum with accumulation of very long chain fatty acids, hypotonia and neuronal migration failure illustrating essential lipid metabolic and detoxification function distinct from energy metabolism.

Ref: Wanders Annu Rev Biochem; peroxisome beta-oxidation VLCFA catalase PTS1 PTS2 Pex import.

View Details
Cell Organelles

The smooth ER plays a crucial role in:

Smooth ER forms anastomosing tubules without ribosomes enriched in enzymes for lipid and xenobiotic metabolism. In hepatocytes it contains cytochrome P450 monooxygenases, NADPH-cytochrome P450 reductase, UDP-glucuronosyltransferases and sulfotransferases that hydroxylate, reduce and conjugate lipophilic drugs, environmental pollutants and endogenous steroids to make them water soluble for biliary or renal excretion. Chronic exposure to phenobarbital induces proliferation of smooth ER increasing detoxification capacity, observed by proliferation of membranes in electron micrographs. Additionally it hosts de novo synthesis of cholesterol, phospholipids, ceramides and steroid hormones from cholesterol via StAR-mediated delivery to mitochondria. Calcium ATPase SERCA pumps calcium into lumen, particularly extensive in sarcoplasmic reticulum of muscle enabling release during excitation-contraction coupling. ATP synthesis via oxidative phosphorylation occurs exclusively in mitochondrial cristae, RNA transcription nuclear, histone modification nuclear, so detoxification defines hallmark smooth ER role linking metabolism to protection. Integration with cell cycle kinases, calcium signaling and mechanical cues ensures coordinated remodeling during growth, migration and differentiation.

Ref: Alberts Ch 12; smooth ER CYP450 detoxification, lipid synthesis, SERCA calcium storage, SAR.

View Details
Microbial Physiology

The primary function of glutathione in bacterial stress response is:

Glutathione is a low-molecular-weight tripeptide gamma-glutamyl-cysteinyl-glycine present at millimolar concentrations up to 10 mM in many Gram-negative bacteria such as Escherichia coli and few Gram-positives that synthesize it via GshA and GshB. Reduced form GSH serves as major thiol buffer and electron donor protecting against reactive oxygen species generated continuously by endogenous respiratory electron transport and by host immune oxidative burst involving NADPH oxidase-dependent production of superoxide during phagocytosis. It directly scavenges superoxide anion, hydroxyl radical and hydrogen and organic peroxides via glutathione peroxidases, forming oxidized glutathione disulfide GSSG that is rapidly recycled by NADPH-dependent glutathione reductase Gor maintaining high GSH to GSSG ratio of greater than 100 to 1. GSH also forms mixed disulfides with redox-sensitive cysteine residues in proteins via reversible S-glutathionylation, temporarily shielding them from irreversible overoxidation to sulfinic or sulfonic acids that require repair. It acts as cofactor for glutathione peroxidases, glyoxalases that detoxify methylglyoxal, and for detoxification of electrophiles and xenobiotics via glutathione S-transferases. Depletion via mutation in gshA renders cells hypersensitive to oxidants, linking its primary role to redox homeostasis rather than to DNA replication or flagellar motility.

Ref: Prescott's Microbiology, 11th ed., Chapter 7: Glutathione and Oxidative Stress Protection in Bacteria.

View Details