Biology Lectures 1 - PDF

# Biological organization - A fundamental basis in medical sciences - The hierarchy of complex biological structures and systems that define life - Each level in the hierarchy shows higher complexity - Each **"object"** is primarily built from the basic units of the previous level ## Hierarchy of...

# Biological organization - A fundamental basis in medical sciences - The hierarchy of complex biological structures and systems that define life - Each level in the hierarchy shows higher complexity - Each **"object"** is primarily built from the basic units of the previous level ## Hierarchy of Living Systems: 1. **Non-cellular organisms:** Viruses - **Simple structure:** Consists of 1 molecule of NA and 1 type of protein - **Complicated structure:** Consists of 1 molecule of NA, several types of proteins (some can have enzymatic function) and of other chemical compounds, mostly lipids - **Morphology:** Helical, ico-sa-hedral (has 20 triangular faces), or complex - **Viruses rely on the host cells to reproduce** - When found outside of host cells, viruses exist as a protein coat or capsid 2. **Unicellular organisms:** - Some of these organisms live in colonies, without specialized roles, each individual cell must carry out all life processes to survive - **Prokaryotes:** Bacteria - **Archae:** similar to bacteria, but some molecular differences, most likely split from bacteria and were the precursors to modern eukaryotes - **Eukaryotes:** Protozoa, unicellular algae (Euglenophyta, Chlorophyta...), unicellular fungi (yeasts, Saccharomyces cerevisiae) - **Multicellular organisms:** most species of animals and plants - **Contain eukaryotic cells** - **Cells can have different structures, based on their function** - **Cells with similar function and structure are organized to form tissues (bones, muscles). Many tissues combine to form an organ.** - **Coordination among organs tissues is managed by: endocrine system and nervous system** - **Most is reproducing sexually. Only gametes can develop into a new individual. Other cells (somatic) can not and highly specialized cells can even loose the ability to divide** - **Multicellular organisms undergo natural selection.** ### Eu-sociality: - The highest level of organization of animal society - Characterized by: - **Cooperative care of offspring** (including brood care of offspring from other individuals) - **Overlapping generations within a colony of adults** (presence of various age groups in the community) - **Division of labor into reproductive and non-reproductive groups.** (individuals within the group specialize in different tasks) - **The division of labor creates specialized behavioral groups within an animal society which are sometimes called castes (ants, bees, termites...)** ### Human being: - Specific development of the nervous system enables thinking ## Cell Theory: - Describes the properties of cells - **Three tenets:** - All living organisms are composed of one or more cells. - The cell is the basic unit of structure and organization in organisms. - Cells come from preexisting cells (Omnis cellula e cellula). - **Modern interpretation:** - The activity of an organism depends on the total activity of independent cells - Energy flow (metabolism and biochemistry) occurs within cells. - Cells contain DNA, which is found specifically in the chromosome, and RNA found in the cell nucleus and cytoplasm. - All cells are basically the same in chemical composition in organisms of similar species. ### The Cell is an open system focused on self-maintenance and reproduction: - **The cell has to be an open system because it needs to exchange matter and energy** - **As an open system, the cell allows nutrients (in the forms of glucose, ions, and many other molecules) to enter the cell and waste products to exit the cell.** - **The cell does this through the use of a semi-permeable membrane.** - **Cells must obtain energy from their environment to maintain constant entropy (stable Ivl of molecular disorder).** - **The genetic material of cells contains all the information that defines their structure and functions (inherited from the mother cell in cell division).** - **But, cells need information also about their environment (chemical composition, presence of nutrients, presence of toxic substances...), in order to be able to adapt.** - **Signaling pathways have evolved to facilitate cell-to-cell communication by transmitting signals often involving movements of ions, solutes, proteins, or secondary messengers from outside the cell.** ### Similarities between eukaryotes and prokaryotes: - Both have cell membranes (outer covering of the cell) - Both have ribosomes - Both have DNA - Both have a liquid environment inside, known as the cytoplasm ## Chemical Composition of Cells: - **Organic compounds:** Proteins, carbohydrates, lipids, and nucleic acids, composed of chemical elements: carbon (C), hydrogen (H), oxygen (O), nitrogen (N), phosphorus (P), sulfur (S) - **Macroelements:** Necessary for cells survival: Potassium (K), Calcium (Ca), Magnesium (Mg), Sodium (Na), Chlorine (CI) - **Microelements:** (trace elements) required in minute amounts: Boron (B), Zinc (Zn), Cobalt (Co), Manganese (Mn), Iron (Fe), med' (Cu), Molybdenum (Mo). - **Inorganic compounds:** Simple compounds of macroelements, mostly without carbon. In cells, they can be in bound state as salts (chlorides, fluorides, carbonates, phosphates…), part of enzymes (Fe in hemoglobin) or as free ions (Na+, Ca2+). - **The most important inorganic compound is water, which makes 60-90% of cell mass.** ## Prokaryotes - Organelles lack a membrane - Ribosomes are the only organelles - Genetic material floats in the cytoplasm (DNA and RNA) - Circular DNA - Unicellular - Cells are smaller in size - Has a larger number of organisms - Appeared 4 billion years ago ## Eukaryotes - Organelles covered by a membrane - Multiple organelles including ribosomes - Membrane covered genetic material - Linear DNA - May be multicellular or unicellular - Cells are larger in size - Have a smaller number of organisms - Appeared 1 billion years ago ## Carbohydrates: - Monosaccharides, disaccharides, oligosaccharides, and polysaccharides - **Mono- and disaccharides** (lower molecular weight) referred to as sugars - **Chemical structure:** Aldehydes (aldose) (C+H +R) or ketones (ketose) (C+2R) with many hydroxyl groups added - **Monosaccharides** with three carbon atoms are called trioses, those with five are called pentoses, six are hexoses, and so on. - **All monosaccharides** (except 1,3-dihydroxyacetone) contain one or more asymmetric carbons, making them stereo centers with two possible configurations each. - **Stereoisomers:** If the hydroxyl group is on the right, the molecule is a D sugar, otherwise it is an L sugar. - **The aldehyde or ketone group of a straight-chain monosaccharide will react reversibly with a hydroxyl group on a different carbon atom to form a hemiacetal or hemiketal, forming a heterocyclic ring with an oxygen bridge between two carbon atoms.** - **Rings with five and six atoms are called furanose and pyranose forms, respectively, and exist in equilibrium with the straight-chain form.** ### Fischer projection - A two-dimensional representation of a three-dimensional organic molecule. ### Haworth projection: - A common way of writing a structural formula to represent the cyclic structure of monosaccharides with a simple three-dimensional perspective. - According to the position of the OH group on the carbonyl carbon, there can be 2 anomers α- and β - **Pentoses:** Are monosaccharides, with 5 carbons. Components of nucleotides (together with H3PO4 and a base) and in some coenzymes. - **Hexoses:** D-glucose, the most abundant monosaccharide, present in fruits and in blood of mammals. - **Galactose:** Is less sweet than glucose and fructose. It is a C-4 epimer of glucose. - **Fructose, or fruit sugar**, is a simple ketonic monosaccharide found in many plants. It is also present in seminal and amniotic fluid. ## Disaccharides: - Composed of two monosaccharide units bound together by a glycosidic linkage formed via a dehydration reaction. - **Maltose** - is formed from two units of glucose joined with an α(1→4) bond. It is produced when amylase breaks down starch. - **Lactose** - a disaccharide composed of one D-galactose and one D-glucose molecule (β1 → 4), occurs naturally in mammalian milk. - **Sucrose** - is composed of one D-glucose and one D-fructose molecule (α-1 → 2). The main form in which carbohydrates are transported in plants ## Polysaccharides: - Common sources of energy - Can be found in cell walls, in intercellular space, bound to proteins, are components of functionally important macromolecules - Molecules composed of long chains of monosaccharide units bound together by glycosidic linkages. - **Starch** - (a polymer of glucose) is used as energy storage in plants - It is a tasteless and odorless powder that is insoluble in cold water or alcohol. - It consists of two types of molecules: - the linear and helical amylose (tightly packed structure, is more resistant to digestion than other starch molecules, so called „resistant starch") - the branched amylopectin - branching takes place with a(1→6) bonds occurring every 24 to 30 glucose units, resulting in a soluble molecule that can be quickly degraded as it has many end points onto which enzymes can attach - **Glycogen** - (a polymer of glucose) used as a form of energy storage in animals and fungi. The main storage form of glucose in the body, serves as energy reserve. A core protein of glycogenin is surrounded by branches of glucose units (may contain 30 000 units). - **Cellulose** - a polysaccharide consisting of a linear chain of several hundreds to many thousands of (1→4) linked D-glucose units. It is a structural component of the primary cell wall of green plants. Used to produce paper. ## Proteins: - Large macromolecules, consisting of amino acid residues - Most proteins consist of 20 different L-α Amino Acid. - All proteinogenic AA have common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bound (except for proline carbon; L-amino group on assymetric carbon is on the left). - **Essential AA** - cannot be synthesized by the organism, but must be supplied in its diet. For humans 9: phenylalanine, valine threonine, tryptophan, methionine, leucine, isoleucine, lysine and histidine. - **The AA in a polypeptide chain are linked by peptide bonds.** - **Once linked in the protein chain, an individual amino acid is called a residue.** - **Protein:** More than 100 AA, shorter are oligopeptides. - **Tertiary structure:** The overall shape of a single protein molecule. - **Quaternary structure:** The structure formed by several protein molecules (polypeptide chains), which function as a single protein complex). ### Typical tertiary structures: - **Globular proteins** - most of them are soluble, many of them are enzymes. - **Fibrous proteins** - often structural, collagen in connective tissue. - **Membrane proteins** - serve as receptors or provide channel for polar or charged molecules. ## Biochemical assemblies: - **Nucleo-proteins** - Association of nucleic acid and protein - **Glyco-proteines** - Consist of both proteins and carbohydrates - **Lipo-proteines** - Consist of proteins and lipids ## Protein denaturation: - When a protein is denatured, secondary and tertiary structures are changed but the peptide bonds of the primary structure between the amino acids are left intact. - The protein can no longer perform its function once it has been denatured. - In very few cases, denaturation is reversible. ## Function of proteins in cells: 1. **Structural support for cells:** - The cytoplasm is highly structured, thanks to proteins. In eukaryotic cells, an extensive network of microtubules, microfilaments, and intermediate filaments can be detected. - **Collagen and elastin are critical components of connective tissue.** - **Proteins can be structurally associated with nucleic acids.** Eg: ribosomes 2. **Enzymes:** Proteins in the cell can be as enzymes, which speed up (catalyze) chemical reactions by lowering the activation energy of the reaction. - Enzymes are highly specific to their substrates. They bind these substrates at complementary areas on their surfaces. - **Isozymes** are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. - **Allosteric modulation:** Allosteric sites are pockets on the enzyme, that bind to molecules in the cellular environment, allosteric interactions can either inhibit or activate enzymes. - **Cofactors:** Some enzymes require non-protein molecules called cofactors to be bound for activity (metal ions, low molecular weight non-protein organic compounds). - Cofactors can be subdivided into: - Either **one or more inorganic ions** - **Or a complex organic or metalloorganic molecule** (coenzyme). Coenzymes transport chemical groups from one enzyme to another (NAD, NADP, ATP, CoA). - **A cofactor that is tightly or even covalently bound to an enzyme is termed a prosthetic group.** ### Phosphorylation and dephosphorylation turn many enzymes on and off: - **Reversible phosphorylation of proteins is an important regulatory mechanism.** - **It causes enzymes and receptors to become activated or deactivated.** - **The addition of a phosphate molecule to a polar R group of an amino acid => turn hydrophobic portion of a protein into a polar and extremely hydrophilic.** 3. **Cell signaling:** Governs basic cellular activities and coordinates cell actions. - **Signals:** Protein (and peptide) hormones (pituitary gland, pancreas, parathyroid). When a hormone binds to a receptor on the surface of the cell, a second messenger appears in the cytoplasm, which triggers signal transduction leading to the cellular responses ### Antibodies (Immunoglobulins): - A large, Y-shaped protein produced by plasma cells, used by the immune system to identify and neutralize pathogens such as bacteria and viruses. ### Regulators of gene activity: - Regulate transcription ### Receptors: - At the surface of a cell. - Act in cell signaling by binding to extracellular molecules. - The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients. - They react with the receptor to induce changes in the metabolism and activity of a cell. - Interaction of a receptor with signal is specific: **The cell can react only to those signals for which it has receptors.** - **Ion channel-linked receptors**: Acetylcholine receptor is linked to a cation channel - **G-protein coupled receptors** - **Tyrosin kinase associated receptors:** Receptors for growth factors and some hormones (insulin) - **Intracellular hormone receptors:** e.g. receptor for glucocorticoids ## Lipids: - Naturally occurring hydrophobic small molecules, including fats, waxes, sterols, fat soluble vitamins, mono-, di-, triglycerides, phospholipids… - **Fats** are a subgroup of triglycerides (ester derived from glycerol and three fatty acids). - **Fatty acids:** Are carboxylic acids with a long aliphyatic chain, which is either saturated or unsaturated (1 - 4 double bonds). - **Important sources of fuel because, when metabolized, they yield large quantities of ATP.** - **Can be:** - **Essential** - must be obtained from food (alpha linoleic acid and linoleic acid) - **Non-essential** - the body can synthesize them - **Numbering of carbon atoms in a fatty acid:** Where C-1 is the -COOH carbo. - **Linoleic acid** is a non-saturated w-6 fatty acid. ### Essential FA: - **Omega-3:** Antiinflammatory (fights inflammation) - α-linolenic acid (mackerel, salmon, cod liver, herrings, o&ysters, sardines, flax seed, chia, walnut, soybeans) - **Omega-6:** Proinflammatory (too much cause inflammation)- linoleic, arachidonic, gamma linolenic acid (walnuts, sufflower oil, tofu, sunflower seeds, peanut butter, avocado oil, eggs, almonds cashews) - **The two carbon atoms in the chain that are bound next to either side of the double bond can occur in a cis or trans configuration.** - In most naturally occurring unsaturated fatty acids, all double bonds are cis bonds. ## Biomembranes: - **A selectively permeable barrier** - **Cell membranes consist of a phospholipid bilayer with integral and peripheral proteins. (50 molecules lipids: 1 molecule protein)** - **Lipids provide a flexible environment for proteins to move and functions.** - **The outer & inner part of the membrane are asymmetrical in their composition serving various function.** ### Phospholipids: - A major component. - They can form lipid bilayers because of their amphiphilic characteristic. - They have a glycerol backbone. - The hydroxyls at C1 & C2 of glycerol are esterified to fatty acids while the C3 hydroxyl is esterified to phosphate. - **Glycerophospholipids:** Can attach to the following polar head groups: serine, choline, ethanolamine or inosito. - **Sphingolipids:** Are derivatives of the lipid sphingosine. - **Glycolipids:** Lipids with a carbohydrate attached by a glycosidic bond. Act as markers for cell recognition and energy sources. - **Cholesterol:** An important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail. - **Cholesterol is largely hydrophobic. But it has one polar group, a hydroxyl, making it amphipathic.** ### Membrane proteins: - **Peripheral:** Watersoluble, with mostly hydrophilic surfaces. Can be easily removed from membranes by conditions that disrupt ionic and H-bond interactions. - **Integral:** Extending into the membrane. - **Often they span the bilayer.** - **Intramembrane domains have largely hydrophobic surfaces, that interact with membrane lipids.** ## Functions of membrane proteins: 1. **Transport:** Proteins in the membrane act like gates or use ATP to pump things in and out. 2. **Enzymatic Activity:** Membrane proteins are like workers with specific tools, helping chemical reactions happen. 3. **Receptors for Signal Transduction:** Proteins on the cell surface catch chemical messages, starting a chain reaction inside the cell. 4. **Intercellular Joining:** Proteins in neighboring cells hold hands, guiding cell interactions and movement. 5. **Cell-Cell Recognition:** Sugar-coated proteins on the cell surface are like ID tags recognized by other cells. 6. **Attachment to the Cytoskeleton and ECM:** Membrane proteins anchor the cell's structure and help cells stick together or move around. ## The Fluid-Mosaic Model of the Cell Plasma Membrane: - Proteins and cholesterol are stuck in the bilayer. - **The phospholipid are not evenly spead out, creating assymetry.** - **Glycolipids are always in the outer layer with the sugar groups exposed at the cell surface, where they form hydrogen bonds** ## Membrane fluidity - Means that lipids can move sideways and across the layers in cell membrane. - This flexibility relies on: - **Temperature:** Low: Crystallized state of membranes shortens the distance between phospholipids/ High - **Cholesterol** (,,buffer''): -- Low: Increases fluidity -- High: Decreases fluidity - **Fatty acids:** -- Saturated: Small distance -- Unsaturated: Increase the distance, increased fluidity - **Biomembranes divide eukaryotic cells to membrane enclosed regions: membrane compartments: mitochondria (25%), endoplasmic reticulum and Golgi apparatus (15%), nucleus (5%).** - **The rest of the cell is cytosol.** ## Function of compartments: 1. To establish physical boundaries for biological processes that enables the cell to carry out different metabolic activities at the same time. 2. Ensure a big inner surface for metabolic processes (enzymes in membranes). 3. Allow to coordinate and regulate these processes by interactions between the compartments. - **Stable localisation of membrane compartments (organelles) is maintained by the cytoskeleton.** ## Plasma Membrane (Cell Membrane) - Defines the boundary of the cell and separates intracellular fluids from extracellular fluids. - Not just a container for the cell, plays a dynamic role in cellular activity ## Glycocalyx: - A thick outer covering of plasma membranes, consists of several carbohydrate moieties of membrane glycolipids, and glycoproteins - A type of identifier that the body uses to differ between its own healthy cells and diseased cells, or invading organisms. ## Functions of glycocalyx: 1. **Protection:** Of the plasma membrane and protects it from chemical injury. 2. **Immunity to infection:** Enables the immune system to recognize and selectively attack foreign organisms. 3. **Defense against cancer:** Changes in the glycocalyx of cancerous cells enable the immune system to recognize and destroy them. 4. **Transplant compatibility:** Forms the basis for compatibility of blood transfusions, tissue grafts, and organ transplants. 5. **Cell adhesion:** Binds cells together so that tissues do not fall apart. 6. **Inflammation regulation:** Glycocalyx coating on endothelial walls in blood vessels prevents leukocytes from rolling/binding in healthy states. 7. **Fertilization:** Enables sperm to recognize and bind to eggs 8. **Embryonic development:** Guides embryonic cells to their destinations in the body. ## Cell Membrane Properties - Semi-Permeable: - The plasma membrane is a selectively permeable barrier. It only allows selected substances to pass through. ## Membrane potential - The difference in electric potential between the interior and exterior of a cell. - **Differences in concentrations of ions on the both sides create a membrane potential (voltage).** - **Ions of sodium (Na+) and chlor (Cl-) with higher concentrations in extracellular space, and of potassium(K+) together with negatively charged proteins with higher concentration inside the cells.** ## Cell Membrane Transport: - **Passive Transport:** Requires no energy input - **Diffusion:** - **Simple diffusion:** - **Facilitated diffusion:** - Ion channels - Carrier proteins - Osmosis - **Active Transport:** Metabolic energy ATP required - **Primary Active Transport** - **Secondary Active Transport** ## Vesicular Transport: - **Exocytosis:** - **Endocytosis:** - Pinocytosis - Phagocytosis - Receptor mediated endocytosis ## Passive Membrane Transport: Diffusion - **Diffusion is when molecules spread out evenly.** - **Molecules move from areas where they are in higher concentration to areas where their concentration is lower.** - **The driving force for diffusion is the kinetic energy of the particles.** - **The speed or rate of diffusion is influenced by: Molecular size (the smaller, the faster), Temperature (the warmer, the faster)** ## Passive Membrane Transport: Simple Diffusion - Doesn't require assistance of membrane protein - **The rate of diffusion depends on how much difference there is between crowded and less crowded areas.** - **Hydrophobic molecules:** O2, N2, benzene - **Small uncharged polar molecules:** Water, urea, glycerol, CO2 - **Lipid soluble substances:** Vitamins ## Passive Membrane Transport: Facilitated Diffusion - Some molecules (glucose, Na ions, and Cl ions) find it hard to pass through the plasma membrane on their own. - **Their transport must therefore be "facilitated" by proteins that span the membrane and provide an alternative route or bypass.** 1. **Carrier proteins** (known as transporters) they pick up specific molecules, change their shape, carry them through the membrane and then let them go. - **Typically, a given carrier will transport only a small group of related molecules.** Eg: hexose transporters - transport glucose and similar monosaccharides into and out of cells. 2. **Ion channels** - these are like tiny tunnels in the membrane. They open and close, allowing specific ions to pass through. Some channels have gates controlled by cells voltage or have a binding site for a ligand which, when bound, causes the channels to open (ligand-gated channels). - **Uniporter:** Involved in facilitated diffusion. They can be either ion channels or carrier proteins. There opening may be regulated by: - **Voltage:** Regulated by the difference in voltage across the membrane - **Stress:** Regulated by physical pressure on the transporter (as in the cochlea of the ear) - **Ligand:** Regulated by the binding of a ligand to either the intracellular or extracellular side of the cell. ## Passive membrane transport: Osmosis - **Osmosis is the net movement of water across a selectively permeable membrane.** - **Water flows from the solution with the lower solute concentration into the solution with higher solute concentration.** - **The energy which drives the process is usually discussed in terms of osmotic pressure.** ## Tonicity: - (tono = Tension) - **The ability of a solution to change the shape (size) or "tone" of a cell by changing the internal water volume.** - **Isotonic:** Solutions with the same solute concentration as the cytosol (0.9% saline or 5% glucose) - **Hypertonic:** Solutions having greater solute concentration than the cytosol. - **Hypotonic:** Solutions having lesser solute concentration than the cytosol. ## Active transport: - Requires metabolic energy (ATP) - **Primary active transport:** - Uses energy derived directly from ATP hydrolysis. - Carrier proteins that can bind specifically and reversibly with the transported atoms/molecules - **Secondary active transport:** - Transport of 2 different molecules across a transport membrane - Uses energy in other form than ATP ### Primary active transport: - Using Antiporter like the Sodium-potassium pump. - Moves 3 sodium ions out of the cell and brings two potassium ions into the cell, requiring energy. #### Synporter: Type of active transport: - **Secondary active transport:** Indirectly uses ATPase (e.g. Na+-K+-ATPase) to create a concentration gradient. - **Ions of Na+ are carried along its concentration gradient and molecules of glucose - against its concentration gradient.** ## Vesicular transport - **Transport of large particles, macromolecules and fluid across plasma and intracellular membranes.** ### Exocytosis: - Moves substance from the cell interior to the extracellular space e.g., molecules of extracellular matrix, extracel. enzymes, blood proteins, immunoglobulins, hormones… - **The vesicles (secretory vesicles) - a fusion with plasma membrane occurs and the content is dumped out to the environment.** ### Endocytosis: - Moves substance from the outside into the intracellular space. - **Phagocytosis:** Pseu-do-pods engulf particles and bring them into the cell. It is a major mechanism used to remove pathogens. - **Pinocytosis:** For uptake of fluid- cell membrane invaginates (infolds) and brings extracellular fluid and solutes into the cell. Pinocytosis is nonspecific in the substances that it transports. The cell takes in surrounding fluids, including all solutes present. - **Receptor mediated endocytosis:** For uptake of specific substances, when the transported substance binds to receptors. ## Cell signaling Cell signaling is like a cellular communication system that manages basic cell activities and coordinates their actions. Cells need to sense and respond correctly to their surroundings for things like development, tissue repair, and immunity to work properly. If there are mistakes in how cells process information, it can lead to diseases such as cancer, autoimmunity, and diabetes. Cells communicate within one organism (intra-organism signaling) and between different organisms (inter-organism signaling). For example, early embryo cells talk to cells in the uterus, and in the human gut, bacteria communicate with each other and with human cells in the intestines and immune system. Signaling molecules are like messengers in our body, telling cells what to do. Hormones are special messengers made by glands, traveling in our blood to control faraway organs. There are three main types of hormones: eicosanoids, steroids, and amino acid derivatives. **Neurotransmitters** are messengers in the nervous system. They include neuropeptides and neuromodulators, released at synapses to communicate between nerve cells and target cells. - **Cytokines:** Small proteins, signaling molecules of the immune system. - **Growth factors:** Can be considered as cytokines or a different class - proteines or steroid hormones, that stimulate cell growth, proliferation and differentiation Cell signaling is divided into three stages: signal reception, signal transduction, and cellular response. ## Intracellular Hormone Receptors: - Are lipid-soluble, they bind to receptors in the cell's cytoplasm or nucleus. - When bound, these receptors join together, enter the nucleus, and trigger the transcription of specific genes. ## Ligand-Gated-Ion-Channel: - Allow passage of small ions (sodium, calcium... ). - Receptor is just a part of the channel. - It works as a channel and receptor. - The bunding of a ligand opens or closes the channel. - They involved in signaling between electrically excitable cells (like neurons and muscle cells). - For example, acetyl-choline receptors found on the muscle endplate are Na channels. ## Enzyme Linked: - Receptor tyrosine kinase - Most of them are single-pass transmembrane proteins. - They have extracellular ligand binding site and intracellular tyrosine kinase area. - Receptors for insulin and some growth factors are receptor tyrosine kinase. - Under inactive state: receptors in monomeric form. - Ligand binding causes Dimerization (the receptors pair up, for insulin present as dimer even under resting conditions.) => phosphorylation => activation of relay proteins. ## G Protein-Coupled Receptors: - Largest family of cell surface receptors. - They mediate response to a wide range of signaling molecules. - On the cytoplasmic side, they associate with G proteins. - And G proteins bind with GTP/GDP. binding of a ligand => series of intracellular events => regulate functions of various enzymes and ion channels. - For example, adr-energic receptors found in cardiac muscle cells. - 2 types of G proteins, heterotrimeric and monomeric. - **The heterotrimeric is composed of 3 subunits alpha beta gamma.** - **Alpha is the one that has GTPase activity. Cycle of subunits of heterotrimeric G proteins during signaling: resting state: Associated with receptor and alpha unit bound to GDP. Binding of ligand causes release of GDP and binding of GTP. => free alpha and beta-gamma complex. Signaling pathways:** - **Adenylyl cyclase:** Produces cAMP - involved in responses to sensory input, hormones, and nerve transmission - **Phospholipase c:** Produces DAG and IP3 - thrombin receptors in platelets use this pathway to promote blood clotting. ## Cell Adhesion and Communication: - Cells use signaling to communicate and coordinate in tissues. - **Adhesive molecules, such as integrins, maintain cell contact, sense the environment, and control cell shape and movement. Junctions like tight junctions, adherens junctions, desmosomes, and gap junctions connect cells in different ways.** - **Transmembrane protein consists of 2 subunits.** - **Connects the extracellular matrix with the actin cytokkeleton inside the cell.** - **Integrin attachments to neighboring cells can break and reform as a cell moves:** - **Tight junctions:** Between cells are connected areas of the plasma membrane that connect cells together. - Forms a strong seal between cells that not even ions can pass across it. - **Adherens junctions:** Join the actin filaments of neighboring cells together - **Desmosomes** - are even stronger connections that join the intermediate filaments of neighboring cells. - **Hemi-desmosomes** - connect intermediate filaments of a cell to the basal lamina, a combination of extracellular molecules on other cell surfaces. - **Gap junctions:** Are clusters of channels that form tunnels of aqueous connectivity between cells (can be found in other tissues as well, many in cardiac tissue). ## Adherens Junctions and Cadherins: - **Cadherins:** Dependent on calcium ions, are transmembrane proteins crucial in forming adherens junctions. - These junctions connect cells by joining their actin filaments. - **Adherens junctions are Composed of cadherins, which bind to the catenins that are connected to actin filaments** ## Cell Signaling Types: - **Autocrine signals:** A cell targets itself. - **Paracrine signals:** A cell targets nearby cells, (neurotransmitters, growth factors) - **Endocrine signals:** A cell targets a distant cell through the bloodstream ## Cell organelles: - **Endoplasmic reticulum: ** - Network of branching tubules and sacs connected to the nuclear membrane. - Function: Central role in lipid and protein biosynthesis. - **Types**: Rough ER (protein synthesis) and Smooth ER (lipid synthesis). => Both types are present in plant and animal cells. The two types of ER are subcompartments of the same organelle - interconnected. - **Cells' Specialization:** Rough ER in protein-producing cells, Smooth ER in lipid and hormone-producing cells. ### Rough ER (Protein Synthesis): - **Appearance:** Studded with ribosomes, giving it a "rough" look. - **The ribosomes bound to it at any one time are not a stable part of this organelle's structure as they are constantly being bound and released from the membrane.** - **Functions**: Site of protein synthesis ### Smooth ER (Lipid Synthesis): - No ribosomes - Function: Lipid Synthesizes most - Fatty acid - Phospholipids - Cholesterol (can become hormones => steroid hormones: testosterone, progesterone, estrogen.) => bud off a particular vesicle which is gonna contain on of them and send then to the cell membrane or GA. - **Cyp450 enzymes** => for detoxification for example the liver has a very high concentrations of these enzymes => biotransformation) - **Contains Glucose-6-phosphatase** converts glucose-6-phosphate to glucose in gluco-neo-genesis. - Location: Glucose formation occurs in the ER lumen - **Stores calcium.** ### Example: Lecithin Synthesis in Smooth ER: - **Process:** Enzymes in ER membrane catalyze reactions from the cytoplasmic side. - **Result:** Lipids inserted into the membrane, polar heads undergo chemical changes. ### Sarcoplasmic Reticulum (SR) in Muscle Cells: - **SR** is like the smooth ER in muscle cells. - **It keeps more Ca2+ than CP.** - **SR's membrane has channels for Ca2+ flow into CP and Ca2+-ATPases to pump them back.** - **Ca2+ signals muscle contraction. STORE AND RELEASE CALCIUM INTO THE MUSCLE.** ### Golgi Apparatus (GA): - Found by Camillo Golgi in 1898, looks like stacked discs (cisternae: collection of cisternae is broken down into cis, medial, and trans compartments) and helps modify, sort, and pack molecules. - GA does glycosylation, cleavage, sulfation, and phosphorylation. - **Transport vesicles move molecules from cis to trans faces.** - **On the side of the Golgi where the vesicles from ER are going to, this is called cis golgi.** - **The side where vesicles are coming out of the golgi towards lysosomes or cell membranes => trans golgi.** - **Resiving vesicles containing proteins and lipids from ER.** ## Modifications of proteins: glycosylation - **N-Type** - **O-Type** ## Phosphorylation of proteins - Packages these molecules. - After packaging, **the vesicles bud off and are stored in the cell until a signal is given for their release.** ## Sulfatatication - Of tyrosins and carbohydrates ## Compartmentalization in GA: - GA's discs have different enzymes for step-by-step processing of proteins. - This keeps processes organized. - **Modifications decide the protein's fate, like adding a mannose-o-phosphate label for lysosomes.** ### Constitutive Secretion: - Transport vesicles from RER to GA are coated with COP proteins. - **Coating disassembles when vesicle touches the target membrane. ** - **COPI goes RER to GA; COP II goes back.** ### SNARE proteins: - A large protein superfamily - Their primary role is targeting vesicles to the correct destination and to mediate vesicle fusion (the fusion of vesicles with their target membrane bound compartments). ### Clathrin-coated vesicles: - Transport from GA to the cell membrane and out of the plasma membrane into endocytosis. - **Protein clathrin forms the outer layer of the coat.** ## Lysosomes: - Contain enzymes: **Hydrolytic enzymes.** Different types: - Proteases - Nucleases - Lipases - Glycosidases (breaks them down) - **Autophagy of organelles:** For ex, ribosom done => vesicle around => lysosomes => ribosomes from protein and DNA => lysosomes break it down. - **Autolysis of damaged cells.** - **Can destroy viruses and bacteria.** - Lysosomal enzymes are synthesized in RER, tagged with mannose 6-phosphate for GA binding. - **Lysosomes maintain pH and prevent their own digestion.** ## Perox