Lecture 7: The Cell: Organelles - Biochemistry I

PBC 201 Biochemistry I The Cell: Organelles Ahmed Fawzy El-Yazbi, BPharm, PhD, BCPS Faculty of Pharmacy Nefertiti El-Nikhely, BPharm, PhD Molecular Biotechnology Program Organelles of the Eukaryoti...

PBC 201 Biochemistry I The Cell: Organelles Ahmed Fawzy El-Yazbi, BPharm, PhD, BCPS Faculty of Pharmacy Nefertiti El-Nikhely, BPharm, PhD Molecular Biotechnology Program Organelles of the Eukaryotic Cells Cells are in a dynamic state of flux Numerous movements occur in the cell where organelles might change their site or shape as they perform their function Each type of organelles contains unique proteins in the interior or in the membrane that perform particular functions Some organelles are surrounded by a single membrane layer, while others have dual membranes (Nucleus, mitochondria) Endosomes Represent an additional method of uptake of extracellular molecules (plus transporters and channels), but can take up soluble macromolecules such as proteins. A part of the cell membrane invaginates into a coated pit, lined by particular proteins (e.g. clathrin). The pit pinches from the membrane forming a vesicle containing the extracellular cargo The vesicle delivers the content into early endosome where the content is sorted. Some of the membrane proteins are recycled back to the membrane, the rest of the content is delivered to the late endosome that fuses with a lysosome. This process is called endocytosis. Lysosome Lysosomal content is acidic and drastically different from the cytosolic environment They degrade components that are no longer required for the cell, a process called autophagy. Material taken up by the cells in endocytosis or phagocytosis (insoluble material) are also broken down in lysosomes. Lysosomal enzymes breakdown macromolecules into their component monomers Nucleases break DNA and RNA, proteases break proteins and peptides, phosphatases remove phosphate groups. Lysosomal enzymes work at an acidic pH provided by H+ and Cl- pumps in the lysosomal membrane (not and neutral pH, consequences of release?) Some diseases result from a defect in lysosomal hydrolysis of cell components e.g. Tay-Sachs Disease (lysosomal storage disorder) is due to decreased breakdown of gangliosides leading to blindness and death.  Perxisomes Contain oxidase enzymes that use molecular oxygen O2 to oxidize susbtrates and release hydrogen peroxide (corrosive). Also contain large amounts of the catalase enzyme to break down hydrogen peroxide. Breakdown fatty acids into acetyl group releasing energy as heat (not like the mitochondria). Acetyl groups are used in the cytosol to synthesize many intermediates including cholesterol. In liver and kidney, toxic compounds can also be oxidized in peroxisomes producing harmless compounds.  The Endoplasmic Reticulum The largest membrane in the cell encloses the endoplasmic reticulum (ER) The ER is formed of an extensive network of flattened membrane-bound sacs called cisternae ER is important in the synthesis of lipids, secreted proteins and membrane bound proteins The smooth ER is called smooth because it lacks ribosomes. The rough ER has ribosomes on its surface. The Smooth ER Fatty acid and phospholipid (phosphoglycerides) synthesis occurs in the smooth ER The liver is particularly rich in smooth ER that contains the enzymes necessary for the breakdown of many hydrophobic chemicals by converting them into more water soluble conjugated products High doses of carcinogens and pesticides induce proliferation of smooth ER in liver cells The Rough ER Ribosomes bind to the surface of the rough ER by the newly formed polypeptide chain Polypetides formed as a part of a membrane or a secreted protein attach and enter the ER through a certain signal polypeptide Membrane proteins remain incorporated in the ER membrane, while secreted proteins accumulate in the ER lumen All cells need membrane proteins so they contain rough ER Rough ER is particularly enriched in cells specialized to secrete proteins e.g. endocrine gland cells secreting protein or polypeptide hormones The Golgi Complex Proteins synthesized in the ER are packed into vesicles that bud off and move to the Golgi Complex The Golgi Complex is a stack of cisternae (Cis-, medial-, and trans-) Vesicles carrying proteins from the ER fuse with the cis side Proteins are modified by enzymes according to their final destination (membrane or secreted) as they move through medial- and then trans- cisternae Other vesicles bud off of the trans-side and carry the proteins either to fuse with the membrane or to be released outside of the cell (exocytosis) The Nucleus The largest organelle of the animal cell Surrounded by two membranes each with a phospholipid bilayer The outer membrane is continuous with the rough ER and the space between the two membranes is connected to the ER lumen The two membranes join at certain areas to form nuclear pores through which certain proteins transport components between the nucleus and the cytosol The nucleus contains nucleic acids with DNA forming chromosomes and RNA being synthesized The nucleolus is a nuclear compartment that is not surrounded by a membrane that synthesizes ribosomal RNA that is assembled with other ribosomal proteins to form ribosomal subunits that move to the cytosol through nuclear pores The Mitochondria They are the main sites of ATP (energy) production during aerobic metabolism They occupy 25% of the cytosol volume Bound by two membranes that differ in composition and function Outer membrane is half lipid, half protein and contains porins (permeable to high molecular weight compounds) Inner membrane is 80% protein (high protein content) with inflodings or cristae that protrude into the matrix Main fuel sources in animal cells are glucose and fatty acids Glucose oxidation starts in the cytosol and then continues in the mitochondrial matrix and inner membrane together with fatty acid oxidation where CO2 is formed The Cytoskeleton The cytoskeleton is formed of three types of filaments: Microfilaments: polymers of actin Intermediate filaments: polymers of different proteins depending on cell type (keratin in epithelial cells, desmin in muscle cells, vimentin in mesenchymal cells) Microtubles: polymers of tubulin Function of the Cytoskeleton It gives the cells its particular shape, binds membrane bound proteins producing structures like villi Support the nuclear membrane and membranes of other organelles Allow cells to adhere to each other and support cells connecting to the extracellular matrix and integrating into tissues Might play a role in force generation in muscle tissue