Modes of Intercellular Signaling

Chapter 1 : Cellular Biology Introduction to Pathophysiology Modes of intercellular signaling ● Cells communicate with each other through various modes of signaling ● Contact-dependent signaling: Cells communicate through close membraneto-membrane contact ● Paracrine signaling: Cells secrete local chemical mediators that quickly affect nearby cells ● Hormonal signaling: Specialized endocrine cells release hormones into the bloodstream to affect distant cells ● Neurohormonal signaling: Neurosecretory neurons release hormones into the bloodstream ● Neurotransmitter signaling: Neurons release neurotransmitters at chemical synapses to directly communicate with the target cells Receptors and signal transduction ● Plasma membrane receptors are categorized into three classes based on their signaling mechanisms ● Cells activate signal transduction pathways in response to external stimuli ● Signals are passed between cells through specific receptor proteins ● Intracellular protein kinases are activated, leading to various cellular responses Classes of Plasma Membrane Receptors ● Receptor Channel: Also called ligand-gated channels; involve rapid synaptic signaling between electrically excitable cells ● Catalytic: Once activated by ligands, function directly as enzymes ● G-Protein: Indirectly activate or inactivate plasma membrane enzyme or ion channel; interaction mediated by protein guanosine triphosphate (GTP)binding regulatory protein (G protein) Signal Transduction Pathway ● An extracellular signal molecule (ligand) binds to a receptor protein on the plasma membrane ● The signal is transduced into an intracellular signal, initiating a signaling cascade ● Different cell behaviors rely on multiple extracellular signals First and Second Messengers ● The first messenger or ligand attaches to the membrane receptor ● Intracellular messengers or second messengers trigger a cascade of intracellular events ● The two major second-messenger pathways are cyclic adenosine monophosphate (cAMP) and calcium (Ca++) Cellular Metabolism ● Cellular metabolism refers to all the chemical tasks of maintaining essential cellular functions ● Energy-using process of metabolism is called anabolism ● Energy-releasing process is known as catabolism What is catabolism? ● Catabolism is the process of breaking down dietary proteins, fats, and carbohydrates into amino acids, fatty acids, and glucose, respectively ● These constituents are absorbed and incorporated into cells and used for various cellular processes, including the production of ATP Role of ATP ● ATP serves as a universal "fuel" inside cells ● It drives biologic reactions and provides the energy necessary for cellular functions ● When organic molecules break down, the chemical energy is transferred to ATP ● ATP stores and transfers energy, and it is converted to ADP and inorganic phosphate during energy-requiring reactions Phases of catabolism ● Phase 1: Extracellular digestion of large molecules to simple subunits (proteins to amino acids, polysaccharides to simple sugars, fats to fatty acids and glycerol) ● Phase 2: Intracellular breakdown of subunits to acetyl CoA, accompanied by production of limited ATP and NADH ● Phase 3: Production of NADH and ATP via citric acid cycle and oxidative phosphorylation, with waste products being excreted Oxidative Phosphorylation ● About two-thirds of the total oxidation of carbon compounds in most cells is accomplished during oxidative phosphorylation ● The major end products of oxidative phosphorylation are CO2 and the dinucleotides NADH and FADH2 ● Oxidative phosphorylation occurs in the mitochondria and transfers the energy from carbohydrates, fats, and proteins to ATP ● During catabolism, electrons are removed from intermediates and transferred to coenzymes like NAD and FAD ● NADH and FADH2 transfer their electrons to the electron-transport chain on the inner surfaces of the mitochondria Anaerobic Glycolysis ● If oxygen is not available, an anaerobic (without oxygen) metabolic pathway called anaerobic glycolysis synthesizes ATP ● Glycolysis occurs in the cytoplasm and converts glucose into pyruvic acid, producing ATP ● In anaerobic glycolysis, pyruvic acid is converted to lactic acid, releasing ATP Citric Acid Cycle ● If oxygen is present, pyruvic acid enters the mitochondria and goes through the citric acid cycle ● The citric acid cycle oxidizes pyruvic acid to acetyl coenzyme A (Acetyl CoA), producing ATP