Basic Cell Biology, major cellular functions: cell division, cellular differentiation and cell death. History of Physiological Vs pathological cell death. Chemistry of lifeEukaryotic cells Vs Prokaryotic cellsCompartmentalization for better regulations of gene expression and other complex biological reactionsCell structureCell typesMajor cellular components:Plasma membraneAn asymmetrical Lipid bi-layerPhasphatidylethenolamine, phasphatidylserine, phasphatidylcholine, sphingomylein, membrane proteins, glycolipids, glycoproteinsCholesterol (important for provide structural rigidity to membrane)Membrane proteins: Receptor proteins, ion channels and transport proteinsFunctions: as barrier between cytoplasm and extra-cellular environment, Controlled transport of chemicals, ions and macromoleculesExocytosis and endocytosisSignal transduction, Generation of action potential

Welcome to the 0359-684: Cell death; Apoptosis, Necrosis and therapeutic opportunities

Endomembrane system in eukaryotic cells

Endoplasmic reticulum:Lipid bilayer forming a continuous sheet enclosing a single space called ER lumen or cisternal spaceRough and smooth ERFunctions: Protein synthesisPost-translational modification (glycosylation Glycolipd synthesisVesicular Protein transport and secretionDetoxification (Smooth ER contain cytochrome P450), water insoluble toxic compounds are converted into excretable non-toxic soluble compoundsCa2++ sequestering: Examples- muscle cells (ER is called sarcoplamic reticulum), nerve cells.Golgi bodies:Membrane bound flattened sacs stacked over each other. Functionally distinct parts (cis and trans parts)Contains protein modification enzymes e.g. glycosyl transferase, nucleoside diphosphatase and acid phosphataseFunctions:Posttranslational modifications (glycosylation, dephosphorylation, phosphorylation)Involved in sorting and packaging macromolecule for secretion or for delivery to other organelles.Proteins destined for delivery to lysosomes are labelled with mannose-6-phospate in Golgi bodies. Defect in this process results in lysosomes without hydrolytic enzymes and secretion of these enzyme in I-cell disease or inclusion cell disease).

Nuclear envelope:

Scanning Electron micrograph of nuclear envelope showing nuclear pores.

Nucleus and Nuclear envelope: ChromatinFunction: Replication, transcriptionProtein import and RNP export across nuclear envelope

Mitochondrial structure

Structure of chromatin

Lysosomes: Membrane-bound vesicles containing hydrolytic enzymes Function:Involved in intracellular digestionPeroxisomes:Membrane-bound vesicles containing oxidative enzymes such as catalase and urate oxidase, and long chain fatty acid oxidation during which there is production of hydrogen peroxide.Functions:Vestige of an ancient organelle that carried out oxidative reactions May play role in anti-oxidative defenceMitochondria:Double membrane-bound structures, power plants of eukaryotic cellsSite for citric acid cycle and oxidative phosphorylation and fatty acid metabolism in energy generating biochemical pathway Outer mitochondrial membraneInter-membrane spaceInner mitochondrial membrane (contains components of electron transport chain, ATP synthase, and transport proteins)Matrix space (contains enzymes and cofactors for citric acid cycle, fatty acid metabolism, mitochondrial genome, and transcription and translation machinery)Inner mitochondrial potential is generated and maintained by proton export out sideATP is synthesis is driven by proton flow towards insideProtein import into mitochondria

Secretory cell of pancreas

Role of solvent i.e. water and solute in the origin of life

Role of solvent i.e. water and solute in the origin of life

Importance of lipids in origin of life

Membrane formation is thermodynamically favorable process

Cellular signalling and cell division

Cellular signalling: Evolution of social behaviour in cellsCell to cell communication and responses are essential for the organism as whole.

Different types of cell signalling: • synaptic• Endocrine• Paracrine • Autocrine• Cell to cell signalling by direct contacts: a) via receptors b) via gap junctions

and plasmadesmata

Extra-cellular signals: • Hormones• Cytokines• Growth factorsSignalling Mechanisms:

• Receptor enzyme mediated• G-protein linked Receptor mediated• Ion-channel-linked Receptor mediated• Intra-cellular Receptor mediated

Ion channel-linked Receptors:

Neurotransmitter receptors NMDA receptors, serotonin, acetylcholine receptors etcBinding----opening of ion channel------influx of Na, or K or Ca ions----downstream eventsDrugs: barbiturates, antidepressants used as blockers

Receptor enzyme mediated:

Receptor tyrosine kinasesExamples- receptors for most of growth factors e.g. FGF, PDGF, Insulin, IGF-1, CSFBinding of ligand to RTK----activation of TK activity------autophosphorylation-----binding of GTPase activating protein or PI3 kinase or phospholipase----Activation of PKC and/or Ras---activation of MAPKKK----activation of MAPKK---Activation of MAPK----c-Jun---activation of transcription

Receptor serine/threonine kinases:Examples- TGF-b family of receptors