CELLULAR PHYSIOLOGY Ass. Prof. Dr. Emre Hamurtekin EMU Faculty of Pharmacy

INTRODUCTION No cell can be called «typical» of all cells. Organelles

CELL MEMBRANE Lipids and proteins, semipermeable Major lipids are phospholipids:  phosphatidylcholine  phosphotidylserine  phosphatidylethanolamine Head: polar, hydrophilic Tail: nonpolar, hydrophobic Glycosphingolipids, Sphingomyelin, cholesterol

CELL MEMBRANE Many different proteins are embedded in the membrane. a) Integral proteins b) Peripheral proteins -CAMs -Pumps -Carriers -Ion channels -Receptors -Enzymes

CELL MEMBRANE Basal lamina Holds cells together, development, growth

MITOCHONDRIA Oxidative phosphorylation!!! ATP : ENERGY

MITOCHONDRIA Have their own genome (less DNA compared to nuclear genome) The enzyme complexes are responsible for oxidative phosphorylation. Through complex I to complex V (ATP synthase), ATP is generated. Ineffective DNA repair system mutations = diseases

LYSOSOMES Irregular shaped structures Surrounded by membrane Interior is more acidic (proton pump, «H-ATPase») Contain hydrolytic enzymes (acid hydrolases) pH:5 Digestion of worn-out cell components, bacteria etc...

PEROXISOMES Contain enzymes (oxidases and catalases) Can form by budding of the ER or division Catalize anabolic and catabolic reactions

CYTOSKELETON System of fibres that maintains the structure of the cell + change shape – Microtubules – Intermediate filaments – Microfilaments Proteins and organelles move along microtubules and microfilaments inside the cell.

CYTOSKELETON Microtubules: – Temperature sensitive – Dynamic portion of the cytoskeleton (provide tracks) – Form spindles which moves the chromosomes in mitosis. – Drugs may affect the microtubules (colchicine, vinblastine, paclitaxel*)

CYTOSKELETON Intermediate filaments: – Connect the nuclear membrane to the cell membrane – Resist external pressure – Cell-type spesific (vimentin: fibroblasts; cytokeratin: epithelial cell) Microfilaments: – Made up of actin – F-actin: intact microfilaments – G-actin: unpolymerized protein actin subunits – Interact with membrane-bound proteins – Microvilli-intestinal mucosa – Lamellipodia – Focal adhesion complexes - Provide tracks

MOLECULAR MOTORS Move proteins, organelles, cell parts (cargo) inside the cell ATPases 3 superfamilies: – Kinesin – Dyneins – Myosin

MOLECULAR MOTORS

CENTROSOMES 2 centrioles + surrounding pericentriolar material Microtubules in groups of three run longitudinally in the walls of each centriole When a cell divides, they duplicate themselves, pairs move apart to the poles of the mitotic spindle, monitor the steps in cell division

CELL ADHESION MOLECULES Cells are attached to basal lamina and to each other by CAMs. – Fasten cells to their neighbours – Transmit signals – Cell movement – Embriyonic development – Formation of nervous system and other tissues – Holding tissues together – Inflammation and wound healing – Metastasis of tumors 4 families: – Integrins – Adhesion molecules of IgG superfamily – Cadherins – Selectins

INTERCELLULAR CONNECTIONS Tight junctions (zonula occludens) Desmosome Zonula adherens Hemidesmosomes Focal adhesions Gap junction

INTERCELLULAR CONNECTIONS Tight junctions: – Surround the apical margins of the cell – Endothelial barrier function – Permit the passage of some ions and solutes in between adjacent cells Desmosomes: – Patches characterized by thickenings of the membranes of two adjacent cells – Intermediate filaments attaches to these thickened areas Zonula adherens: – Major site of attachments for intracellular microfilaments Hemidesmosomes & Focal adhesions: – Attach cells to underlying basal lamina – Labile structures associated with actin filaments inside the cell – Play an important role in cell movement

GAP JUNCTION Connexons are lined up with one another to form gap junction.

NUCLEUS & RELATED STRUCTURES The nucleus is made up in large part of the chromosomes. Each chromosome is made up of DNA. DNA is wrapped around a core of histon protein to form a nucleosome. The whole complex of DNA and proteins is called chromatin.

NUCLEUS & RELATED STRUCTURES The nucleus of most cells contain nucleolus. Rich in RNA. They synthesize the ribosomes. Nuclear membrane is a double membrane. Spaces between the two folds are called perinuclear cisterns.

ENDOPLASMIC RETICULUM ER is a complex series of tubules in the cytoplasm – Rough (granular) ER: protein synthesis – Smooth (agranular) ER: steroid synthesis & detoxification Sarcoplasmic reticulum: skeletal and cardiac muscle

RIBOSOMES 60S AND 40S subunits These are the sites of protein synthesis. Ribosomes attached to ER synthesize: – all transmembrane proteins – most secreted proteins – most proteins stored in Golgi, lysosomes, endosomes Free ribosomes synthesize: – Cytoplasmic proteins (i.e. hemoglobin) – proteins found in peroxisomes and mitochondria.

GOLGI APPARATUS Glycosylation of proteins and lipids.