VPhy 101: Veterinary Physiology Midterm PDF

VPhy 101: Veterinary Physiology Topic 2: Introduction to Physiology  William Harvey (1628) - authored book on the circulation of blood on 1682 - Physiology is about functions...

VPhy 101: Veterinary Physiology Topic 2: Introduction to Physiology  William Harvey (1628) - authored book on the circulation of blood on 1682 - Physiology is about functions (starting point of physiology) - Study of the functions of the organisms - “An anatomical study of the heart and of the blood in - It answers and explains the process of how life works animals.” - an integrative discipline which foundation lies from - Humans and other mammals reproduced via homeostasis and integration. fertilization of an egg by sperm  Consolidation (1750) - Emmanuel Kant & F.J.W. von  Importance: Schelling  Understanding animal life in health - standstill of European Medical Science  To explain the physical and chemical factors that - rise in philosophical idealism in Germany: the are responsible for the origin, development, and intelligent human is able to understand the natural progression of life. phenomena; the experiment-based approach was not  Appreciation of emerging discoveries in genetic necessary engineering  Rebirth of Physiology (1840)  Understanding of new techniques for detecting - rise of great physiologist Carl F.W. Ludwig (kymograph) and treating disease in Germany  Use of published facts on how stay healthy - Claude Bernard (experimental medicine-homeostasis)  Provides foundation needed to support clinical in France experiences of vet met students - Charles darwin and Demetri Mendelev (part of general  Application: revival of science)  To know the abnormal, (disease, anomaly, - Charles darwin introduced the book “Origin of Species” misfunction) a competent veterinarian must first on 1859 know what is normal. - Dmitri Mendelev introduced the “periodic table of  To treat effectively, a veterinarian must know which elements” on 1869 function of the body is compromised and how to - WIlliam Beaumont who specialized in gastrointestinal intervene. physiology  Serves as baseline for medical research thus - during this time, specialized branches of science formulating intervention to abnormal physiological appeared such as Gastrointestinal Physiology. processes is much easy. - Rudolf Virchow specialized in Pathology and Cell  Adaptation Physiology -Louis Pasteur, Ignaz Semmelweis, and Robert Koch, who specialize in Bacteriology. - Claude Bernard (Birth of Integrative physiology) and was the first General Physiologist of his time. - Carl Ludwig and Edward Pfluger(Germany) = Integrative physiology - Francisco Donders (Netherlands) = Integrative physiology - Founding of new journals: - ability of organisms to adapt to any changes either ►1858 - Archiv fur pathogische Anatomie und in terms of environment or mutations. Physiologie und fur klinische Medicin by R. Virchow - a tokay gecko cannot climb in walls, however, they and B. Reinhardt (Virchow’s Archive needed to evolve in order to survive by eating ►1868 - Pflugers archiv (Pfugers archiv Europian insects that fly around. Thus, the gecko’s body Journal of Physiology) evolved its foot pads which consists of many ►1878 - First Journal of Physiology lamellae, making them able to stick to walls. ►1898 - The American Journal of Physiology ►1906 - The Journal de Physiology (Paris) ►1889 - Skandinavbiches Archiv fur HISTORY OF PHYSIOLOGY Physiologie, the predecessor of Acta Physiologica - 19th and 20th Century -other physiologist were known: ►Ivan Pavlov - Psychophysiology ►Charles Sherington - Neurophysiology ►Otto Frank and Ernest Starling - Cardiovascular physiology and hormones ►Angelo Mosso - ergograph and sphygmomanometer ► Camillo Golgi - nervous system and malaria ►Sydney Ringer - Ringer’s solution  ►Francois Magendie - Magendie sign - the tendency toward a relatively stable ►Willem Einthhoven - electrophysiology (Nobel equilibrium between interdependend Prize) elements, especially as maintained by  Start of IUPS or Intl Union of physiological physiological Societies (1953) - body’s ability to maintain a stable - Organization of physiologist in national environment. physiological societies ` - Ex: - separation of physiology from pharmacology ►When the blood pressure of an animal - First meeting of physiologists rises, the RAS system would help - 1st international congress of physiological in Basle, lowering blood pressure and giving Switzerland in 1889 away the excess electrolytes and salt,  In 1997, the American Journal of Physiology splits therefore, dragging water out also. in sections - International Union of physiological Scientist was created in Denmark - Formation of Federation of European Physiological Societies FEPS (Acts Physiologica is official journal)  In 2000, the Physiome begins - 1970- research in the medical sciences became divided into numbers of specialized areas (cell biology, molecular biology, genomics, and protein biology) VPhy 101: Veterinary Physiology Topic 3: Homeostasis and Integration -The foundation of Physiology “A theory: Life is a system that tries to regulate itself to preserve its identity.”  CELL - basic unit of organisms ►Self-organization ►Self-regulation ►Support and movement  Interdependent relationship of cells, body systems, and homeostasis. The depicted interdependent relationship serves as a key foundation for modern- day physiology; homeostasis is essential for the survival of cells, body systems maintain homeostasis, and cells make up body systems.  Factors of interval environment that are often homeostatically regulated:  Concentration of energy rich molecules = (glucose, proteins, amino acids,  Hemostasis monosaccharides, fatty acids, nucleic acids, - the ability of the body to form blood clots minerals, etc.) to support the energy regulation when cut by a sharp object to stop the and structure and must be homeostatically bleeding. regulated.  Homeostasis  Concentration of O2 and CO2 = cells need O2 - the ability of the body to put itself in an and CO2 should be released to avoid acidosis equilibrium.  Concentration of waste product = CO2 and urea, - “ Le milieu interieur” or mammals has the etc. ability to maintain relatively constant state of  pH (maintain a 7.4 to avoid suffering from internal environment” - Claude Bernard acidosis and alkalosis. -greek word homeo (similar) + statis  Concentration of water, salts, and other - maintaining integrity in the face of electrolytes = function of the kidneys and must disturbances be homeostatically regulated   Volume and pressure = regulated by the  Thermoregulatory System cardiovascular system and kidneys ►Sensors - heat receptors  Temperature = regulated by the ►Integrator - hypothalamus thermoregulation system ►Effector - sweat glands (to cool off  Social parameters and heat up)  Animals vary in their homeostatic abilities  Positive Feedback Mechanism - the output is continually enhanced so that the  Regulators - mammals, humans controlled variable continues to move int the  Conformers - they can conform to what’s direction of the initial change. possible; such as brine shrimps - reinforces the change in the same direction.  Avoiders - capable of migrating; monarch butterfly  Two Regulatory Mechanisms  Negative Feedback Mechanism - occurs when there is a change in a controlled variable which triggers a response to oppose the change, driving the variable in the opposite direction of the initial change - example: High blood pressure it oppose the highblood pressure to lower the blood pressure.  Sensor  Integrator  Effector  Integration - the cells, systems and whole organism has an Integrated relationship.  Renin-angiotensin-aldosterone system →also an example of a negative feedback mechanism → a controlled variable, once it is detected by the →when there is a decrease in renal perfusion or blood sensor, and the sensor will send signal to the pressure, the juxtaglomerular apparatus would actually integrator(set point, either increase or decrease detect it. And this would send a signal to that particular variable), and the integrator sends it to the effector, part of the kidney, which is the juxtaglomerular which do its thing. But in the presence of incoming apparatus to produce renin. Renin will go to the disturbances, a sensor could detect it and then there is circulation, and it would send signal to liver and liver an anticipator which activates corrective response would actually make angiotensinogen. This will be then before the variable is restored. converted wit the presence of the renin, and will become the angiotensin 1. angeotensin 1 will now be converted  The Nervous System into a more powerful hormone called Angeotensin 2 by - Acts through electrical signls to control rapid the ACE, which is actually made or produced from the responses of the body; lungs., particularly from the surface of the pulmonary - also responsible for higher functions. and renal endothelium or ACE.Angeotensin 2 would  Endocrine System actually increase the sympathetic activity, this would be - acts by means of hormones secreted into the the increase of beat and the rate of the beating of the blood to regulate processes that require duration heart. rather than speed → Angeotensin 2 would actually promote tubular sodium - examples: metabolic activities and water and and chloride re-absorption and potassium excretion. electrolytes balance. Therefore, it would promote H2O retention. So in the  Respiratory System tubules of the kidneys, sodium, chloride and water would - obtains O2 from and eliminates CO2 to the be reabsorbed. Also, in the adrenal gland cortex, it external environment would trigger the release of aldosterone and this would - helps regulate pH by adjusting the rate of removal reinforce the tubular sodium chloride reabsorption and of acid-forming CO2 water retention.  Excretory System or Urinary System →it would also increase anteriolar vasoconstriction and - important in regulating the volume, electrolyte increase in blood pressure. composition, and pH of the internal environment →Another one, in the pituitary gland or posterior lobe of - removes wastes and excess water, salt, acid, and the pituitary gland, it would trigger the release of ADH other electrolytes from the plasma and eliminate secretion. ADH(Antidiuretic hormone) secretion would them in the urine. make the collecting duct of the kidneys reabsorb H2O.  Digestive System all in all, water retention will be possible, effective - obtains nutrients, water, nd electrolytes from the circulating volume increases, and perfusion of external environment and transfers them into the juxtaglomerular apparatus increases as well. And then, plasma when water and salt retention is actually happening, the - eliminates undigested food residues to the presence of good perfusion of blood would actually send external environment. a negative feedback to the kidneys to stop producing  Reproductive System renin. When the production of renin stops, the - not essential for homeostasis, but essential for conversion of angioteninogen to angeotensin 1, and perpetuation of the species. then from ACE angeotensin 1 to angeostensin 2.  Circulatory System - transports nutrients,O2, CO2, wastes, electrolytes, and hormones throughout the rest of the body. The Physiological Systems of the Body  Muscular and Skeletal System - support and protect body parts and allow body movement - heat-generating muscle contraction are important in temperature regulation - calcium is stored in the bone.  Immune System - defends against foreign invaders and cancer cells - paves way for tissue repair.  Integumentary System - serves as a protective barrier between the external environment and the remainder of the body - adjustments in skin blood flow re important in temperature regulation.  Organ systems can be grouped according to whole- body contributions Whole body control systems (2) Support and movement systems (2) Maintenance systems (7) Reproductive system (1)  Integration VPhy 101: Veterinary Physiology - physiology I an integrative discipline Topic 4: functional Organization of the Body Anatomy Physics  Physiological Organization Chemistry Pathology 1. Molecules 2. Cells\tissue Biochemistry Pharmacology 3. Organ Molecular Biology Genetics 4. System 5. Organism  Anatomy  Physiological Systems  Nervous - regulatory system; at the top of everything  Endocrine - major integrator and regulator of the body system  Immune - responsible for immunity and protection from  Anatomy, physiology foreign invaders  Respiratory - transport and diffusion of CO2 & O2  Digestive - important in the digestion of food  Urinary - excretion of waste product and reabsorbing anything that can be reabsorb  Integumentary - helping in thermoregulation and protection from the harsh environment environment  Circulatory - delivering nutrients and other chemicals in the receptor cells in the body  Lymphatic - important in returning blood or fluid  Reproductive - in proliferation of species  Muscular - support, structure and locomotion  Anatomy, physiology, and Pathology  Skeletal - support, structure, and locomotion  Molecular Physiology Organic & Inorganic Molecules: 1. Carbohydrates 2. Fatty acids/fats 3. Amino acids and protein 4. Nucleic acids/Nucleotides 5. Water 6. Other inorganic molecules →these are important because they form or the base line of the body. The body cannot function fully without these. These molecules form the structural component of the cells.  Central Dogma of life: transcription and translation - the DNA is transcribed into RNA in the nucleus; RNA is translated in the cytoplasm. Prokaryotic cells do not have a nucleus; transcription and translation proceed in their cytoplasm.   Amino acids - provides energy as osmolytes - Serves as signal molecules  Proteins -forms signal molecules and receptors - transporters  Gene transcription in Eukaryotes - located in the cell membrane and inside since the organelles are somewhat made up of proteins - transmembrane receptor; G protein coupled receptors; Important since there are certain  Carbohydrates (CHO) processes that needs since this is the only link - the dominant energy molecules for of the outside link to the inside link animals - when a specific ligans - important energy storage molecule in - carrier and channel proteins animals - they could become a building blocks for - forms important structures (cell walls hormones (insulin hormone) by the cellulose and arthropods - structural and functional component exoskeleton by chitin) - part of an enzyme (ex.: in muscles: troponin, - attached to proteins to form tropomyosin) glycoproteins (cell membrane and signaling systems)  Fats - provides energy - serves as signal molecules - more potent source of energy, but not the preferred one since we prefer glucose and carbohydrates - has more carbons, more powerful than a glycogen when it comes to - a complex structure of proteins mainly energy production determine by weak bonds between amino acid - used to make membranes side groups allowing proteins to be dynamic (phospholipids and cholesterol) and flexible or also known as alosteric activity or - used to make steroids and bile characteristic. - lipids are important to repel substances that enter the cell or any part of the inner cell  VPhy 101: Veterinary Physiology Topic 5: Cellular Physiology Cells are distinct from inanimate constituents with their capabilities: 1. Ability to Grow - from a unicellular organism, to a formation of many other cells via mitosis, it would become a multicellular organism along with the development will be the formation of tissues, to organs, to a system, and then as a whole function of a organism. Figure 1-1; three common mechanisms of allosteri shape change in proteins. A. Ligand binding. Ligand binding to a allosteric site (site B) on a protein changes the protein’s conformation such that binding site A is altered; ligand no Ex.: muscle fiber - it would grow in size but not in longer binds at site A because of the binding event at site B. B, number also called hypertrophy mio-fibrillar Phosphorylation. Addition of phosphate group to a serine, hypertrophe a muscle that is not being used is small, threonine, or tyrosine residue of a protein alters the protein’s bt when a muscle is used, it would grow. There will conformation, changing its binding characteristics. In this be addition of nuclei to make it larger. Muscle would hypothetical example, phosphorylation activates an not add muscle fiber, but undergo miofibrillar otherwise inactive protein. Some proteins inactivate by this hypertrophe. mechanism. ATP, Adenosine Triphosphate; ADP, adenosine diphosphate. C, Voltage-dependent proteins. The 2. Replicate conformation of some proteins, particularly ion channels, is - two processes: by the process of mitosis, where the altered by the electrical field surrounding the protein. Shown female gamete will separate into two daughter cells, here is the opening (activation) of a voltage-dependent, and these will proliferate for reproduction. Also, there is gated CA2+ channel when the membrane depolarizes. meiosis, where the parent cells will produce two daughter cells, and then produce more daughter cells.  Nucleotides nd nucleic acids -contains codes in a form of genes for making RNAs and proteins. 3. Perform Complex Metabolic Reaction  Water (H2O) - one of the best example of this is the aerobic respiration inside the cell such as the Kreb cycle. - universal inorganic molecule of life on KREB cycle or Tricarboxylic acid cycle, where the use of Earth monosaccharides like glucose and will become an - sometimes called universal solvent engine for the production of the refined fuel or ATP that - dehydration is one the main reason of would let the particular cell go on its basic function. death in the pet industry - water serves as a medium for reaction of life 4. Respond the Environmental Stimuli - like how the special receptors that once a stimulus is detected, they wold actually response to the stimuli.  Membranous Organelles in the Cytoplasm:  Endoplasmic Reticulum  Cell Structures Visible in an Electron Microscope - extensive, continuous memrbanous network of fluid- filled tubules and flattened sacs, partially studed with ribosomes. - forms new cell membrane and other cell components and manufactures products for secretion  Golgi Complex - sets of stacked, flattened membranous sacs - modifies, packages, and distributes newly synthesized proteins  Lysosomes - membranous sacs containing hydrolytic enzymes - serves as cell’s digestive system, destroying foreign - all cells have to major subdivisions: cytoplasm and substances and cellular debris the plasma membrane - Eukaryotic cells: Nucleus - houses the DNA  Peroxisomes - membranous sacs containing oxidative enzymes  Plasma membrane - perform detoxification activities - phospholipid bilayers composed  Mitochondria of two fatty acids which aggregate - rod or oval-shaped bodies enclosed by two with each other to form the membranes, with the inner membrane folded into plasma membrane, and making cristae that project into an interior matrix the outer layer hydrophilic and the - acts as energy organelles; major site of ATP production; inside is hydrophobic. contain enzymes for citric acid cycle, proteins of - a very thin oily barrier that electron transport system, and ATP synthase. encloses the cell, separating the cell content from the surrounding  Non-Membranous Organelles in the Cytoplasm environment  Ribosomes - do not serve only as a mechanical - granules of RNA and proteins - some attached to rough barrier to hold in content of the ER, some free in cytosol cell but selectively control - serve as workbenches for protein synthesis movement of many molecules. - there are proteins within the bilayer: channels,  Proteosomes receptors, and glycoproteins, which are important - tunnel-like protein complexes in cell signaling and movement of ions and nutrients - serve to break down unwanted proteins or even communication of the inside to the outside of the environment.  Vaults - composed of phospholipids, cholesterol, proteins - shaped like hollow octagonal barrels and glycoproteins - serve as cellular truck for transport from nucleus to - water, CO2 and small hydrophobic molecules can cytosplasm easily diffuse.  Centrosomes/Centrioles  Cytoplasm - a pair of cylindrical structures at right angles to each -gel-like part where most of the cell organelles are other (centrioles) surrounded by an amorphous mass located - form and organize the microtubule cytoskeleton. - portion of the cell interior which is not occupied by the nucleus - contains number of discrete specialized organelles and cytoskeletons dispersed within the cytosol.  Cytosol  Transcription  Intermediary Metabolic Enzymes - Gene in a DNA - dispersed within the cytosol - RNA polymerase - facilitate intracellular reactions involving degradation, - Pre-mRNA synthesis, and transformation of small organic molecule - MAture-mRNA  Transport, Secretory, and Endocytic Vesicles  Translation - transiently formed, membrane-enclosed products - rRNA synthesized within or engulfed by the cell - ribosomes - transport and/or store products being moved within, - tRNA out of, or into the cell, respectively  Inclusions - glycogen granules, fat droplets - store excess nutrients  Cytoskeleton - as an integrated whole, serves as the cell’s “bone and muscle”  Microtubules - long, slender, hollowtubes composed of tubulin  All cells in the body has same set of genetic material molecules  Different cell types transcribe different sets of genes - maintain asymmetric cell shapes and coordinate Ex.: only hemoglobin is only produced by RBC complex cell movements, specifically serving as highways for transport of secretory vesicles within cell,  How is this differential gene expression serving as main structural and functional component of accomplished? cilia and flagella, and forming mitotic spindle during cell division. Epigenetics: switching genes on and off  Microfilaments - intertwined helical chains of actin molecules; 1. Regulation of individual genes with promoters microfilaments composed of myosin molecules also and transcription factors present in muscle cells 2. Regulation of transcription factors in different - play a vital role in various cellular contractile systems, tissues and at different stages. including muscle contraction and amoeboid movement; serve as a mechanical stiffener for microvilli  Insulin Secretion  Intermediate Filaments - insulin receptor tyrosene- kinase - irregular, threadlike proteins - once the insulin or ligands bonds to it, the beta - help resist mechanical stress subunit of beta tyrosene kinase receptor would actually phospholyrate, there will be  Nucleus phosphorylation of the enzyme. Metabolic - largest single organized cell functions would trigger phosphatydilinostiol 3- component usually located near Kinase signaling pathway, so there will be synthesis the center of the cell of lipids, proteins, and glycogen, and also cell - has outer envelope and has an survival and proliferation. And then, this outer and inner membrane, it has phosphatydilinositol 3K pathway would actually a nucleolus, nucleoplasm, allow this receptor called GLUT transporters, which chromatin, some ribosomes, and allow to dock the plasma membrane of a particular nuclear pore place such as the muscle, tissues, and every cell in - contains the materials for genetic the body which needs insulin. That’s the reason instructions and inheritance why insulin enters the body. There are other - in-houses the DNA factors that are involved. - packaged with proteins called histones in the nucleus to form complexes called chromosomes - indirectly governs most cell activities - serves as the cell’s control center  DNA- has two important functions; 1. Providing a code of information for RNA and protein synthesis and; 2. Serving as a genetic blueprint during cell replication (for genetic inheritance)  Ribosomes 3. The transport vesicles fuse with the Golgi complex, open - ribosomal RNA- protein up, and empty their contents into the closest Golgi sacs. complexes that synthesize proteins, 4. The newly synthesized proteins from the ER travel by indirectly under the direction of vesicular transport through the layers of the Golgi complex, nuclear DNA which modifies the raw proteins into final form and sorts and - important in protein synthesize directs the finished products to their final destination by right after the transcription and varying their wrappers. translation process. 5. Secretory vesicles containing the finished protein products - has two locations: bud off the Golgi complex and remain in the cytosol, storing 1. Unattached or ‘free’ ribosomes the products until signaled to empty. are dispersed throughout the 6. On appropriate stimulation, the secretory vesicles fuse cytosol with the plasma membrane, open, and empty their contents 2. Bound ribosomes are found on to the cell’s exterior. Secretion has occurred by exocytosis, membranes of a major organelle, with the secretory products never having com into contact the endoplasmic reticulum (ER) with the cytosol. 7. Lysosomes also bud from the Golgi complex.  Endoplasmic Reticulum - an elaborate, fluid filled membranous system  Specialized ER’s distributed extensively throughout the cytosol, wwhere Liver -SER it is primarily a protein-manufacturing factory - Contains enzymes specialized for detoxifying toxic - two distinct types--rough and smooth-- can be compounds produced within the body by the distinguished. metabolism of substances that enter from the - the rough has sacs while the smooth has tubules. outside (such as drugs and plant toxins)  Golgi Complex - consists of sets of flattened, slightly curved membrane- enclosed sacs, or cisternae, stacked in layers which closely associated with ER. - two major function: 1. Processing the raw materials into finishing products. 2. Sorting and directing the finished products to  ER in a electron-micrograph their final destinations.  Exocytosis - a secretory vesicle fuses with the plasma membrane, releasing the vesicle contents to the cell exterior. The vesicle membrane becomes part of the plasma membrane.  Endocytosis - materials from the cell exterior are enclosed in a segment of the plasma membrane that pockets inward and pinches off an endocytic vesicle - the ER is though to be a continuous organelles with many interconnected channels. The relative amount of smooth and rough ER varies between cells, depending on the activity of the cell. The more active the cell is, the bigger in number the ERs are. - the secretory vesicle would be released from te golgi apparatus. This then would undergo uncoatin (the coatomer would be uncoated), making what remains the three: V-snare (docking marker), recognition marker, coat protein receptor. These three are aggregated by each other. There 1. The rough ER synthesizes proteins to be secreted to the also the presence of sorting signals. This exterior or to be incorporated into the cellular membrane particular secretory vesicle, with the 2. The smooth ER packages the secretory produced into the presence of stimulus, they would travel transport vesicles, which bud off and move to the Golgi from the cytosol to the plasma membrane complex. where these vesicle would dock. When  there is a docking, the v-SNARE would dock to the - dynamic facilitates the pinching off of endocytic t-SNARE or the docking-marker acceptor. vesicle/s  Receptor-mediated Endocytosis - a highly selective process that enables cells to  Lysosomes and Proteasomes import specific large molecules that the cell needs - functions as an important part in breaking down from its environment unwanted materials - triggered by the binding of a molecule such as a - full of hyrolytic enzyme mixture in the lysosomes protein to a specific surface membrane receptor Ex.: Glycosidases, Proteases, & Sulfatases site - being the digestive system of a cell by not needing - Clathrin facilitates pouch forming (coated pit) anymore proteins and just can recycle. - Cholesterol complexes, vitamin B12, the hormone - are small organelles that break down organic insulin, and iron are examples of substances molecules (lys means “breakdown”; some selectively taken into cells by receptor-mediated means “body”) endocytosis - lysosomes vary in size and shape, depending on the contents they are digesting - Most commonly, lysosomes are small (0.2 to 0.5 mm in diameter) oval or spherical membrane-bound bodies. - On average, a cell contains about 3000 lysosomes -Each lysosome contains more than 30 different hydrolases synthesized in the ER to the Golgi complex for packaging into the budding lysosome. -Lysosomal enzymes are similar to the hydrolytic - Unfortunately, some viruses can sneak into cells enzymes that the digestive system secretes to digest by exploiting this mechanism. For instance, flu food. Thus, lysosomes serve as the intracellular viruses and HIV/ FIV (helper T cells), the viruses “digestive system.” that cause human and feline AIDS respectively, -Lysosomes digest extracellular material brought into gain entry to cells via receptor-mediated the cell by phagocytosis endocytosis. They do so by binding with membrane receptor sites normally designed to trigger internalization of a needed molecule.  Phagocytosis - During phagocytosis (“cell eating”), large multimolecular particles are internalized - only a few specialized cells are capable of phagocytosis known as “professional” phagocytes, the most notable being the immune cells that are crucial defense mechanisms in all animals (neutrophils and monocytes/macrophages)  Endocytosis - Pseudopods are used to engulf worn out - the internalization of extracellular material within a materials/foreign invaders cell (endo means “within”). - lysosome fuses with the membrane of the - can be accomplished in three ways—pinocytosis, internalized vesicle and releases its hydrolytic receptor mediated endocytosis, and phagocytosis— enzymes into the vesicle, where they attack the depending on the contents of the internalized material trapped materials without damaging the rest of the and the cell type cell -Most body cells perform pinocytosis, many carry out receptor-mediated endocytosis, but only a few specialized cells are capable of phagocytosis.  Pinocytosis - cell drinking - a droplet of extracellular fluid are taken up non- selectively  Lysosomes: Functions ubiquitin molecule carried by the E3 is broken off Lysosomes remove worn out organelles and transferred to the protein. The cycle repeats - can also fuse with aged or damaged organelles to until the protein is tagged with a chain of remove parts of the cell. This selective self-digestion ubiquitins. This chain binds to the proteasome, makes way for new replacement parts. which allows enzymes near the opening of the Can rupture to kill a whole cell when that cell is proteasome’s chamber, where other enzymes severely damaged chop it to pieces. Causes intentional self destruction of healthy cells. This happens as a normal part of embryonic  Peroxisomes development when certain unwanted tissues that - several hundred small peroxisomes that are about one form are programmed for destruction. third to one half the average size of lysosomes are present in a cell - house several powerful oxidative enzymes and contain most of the cell’s catalase  Proteasomes -a large tunnel-like structure made of numerous proteins - Proteasomes destroy internal proteins - Oxidative enzymes, as the name implies, use oxygen - Cells has thousands of it (O2), to strip hydrogen from certain organic molecules. - uses specialized enzymes can detect worn out/to be This reaction helps detoxify various wastes produced destroyed proteins and “tag” them with a tiny within the cell or foreign toxic compounds that have protein called ubiquitin. entered the cell, such as ethanol that is consumed in - ubiquitin-tagged protein is then recognized by alcoholic beverages. the proteasome and drawn in to its disassembly - Hydrogen peroxide (H2O2), is formed by molecular Tunnel oxygen and the hydrogen atoms stripped from the toxic molecule. - Hydrogen peroxide is potentially destructive if allowed to accumulate or escape from the confines of the peroxisome. - However, peroxisomes also contain an abundance of catalase, an enzyme that decomposes potent H2O2 into harmless H2O and O2. - This latter reaction is an important safety mechanism that destroys the potentially deadly peroxide at the site of its production, thereby preventing its possible devastating escape into the cytosol.  Process for Targeting a Protein to a Proteasome for Degradation - this process requires  Mitochondria three enzymes working in - the energy organelles or “power plants” of the cell concert to tag the ill-fated - they extract energy from the nutrients in food and prtein with a chain of transform it into a usable form to support cell activities ubiquitin molecules. The - usable form which is the very refined fuel also called first enzyme (E1) binds to ATP. and activates a - the more high-limit metabolizing a cell is, the more ubiquitinmolecle and then mitochondria present in a cell. hands it off to the second - About 90% of the energy that cells—and, accordingly, enzyme (E2), which in turn that tissues, organs, and the whole body—need to joins to a third enzyme (E3). survive and function is generated by mitochondria E3 enzymes are like socket - Mammalian organ most dependent on mitochondrial wrenches that fit various energy production is the: Brain, heart, skeletal muscle, target proteins using the kidneys, & hormone-synthesizing tissue. “sockets” called F-box proteins. When an E3 binds to a protein, the  - these organs, mitochondria is more numerous compared to the rest of the not mentioned organs above.  Mitochondria: Site of Major Energy Production  Mitochondria: Morphology → generally rod- or oval-shaped structures about the size of a bacterium → Considerable evidence point that mitochondria are descendants of bacteria - after the mechanical digestion of food, it will be subjected into enzymatic digestion in the small intestines. Once absorbed in the small intestine, wherein the bulk of absorption of these particular nutrients take place, individual nutrients, even the smallest nutrient possible that could actually pass the small intestine could be the monosaccarides, fatty acids, amino acids, and many more. For example glucose, another of component of mitachondrial metabolism is the CO2, and these will be inspired by the lungs, diffusing  Mitochondrial DNA (mtDNA) these inside the body coming from the alveoli to the RBCs. → exclusively inherited from the maternal side And once diffused in the lungs, it will go into the circulation →contains genes for producing many of the where this oxygen will also be carried into the circulation, molecules mitochondria need to transduce and meet the glucose there. These will then be absorbed by energy the cell. Once present int he cell (cytosol), this is where → flaws gradually accumulate in mtDNA over an glycolysis would take place. So the glucose itself would animal’s lifetime undergo glycolysis and will be split up into two pyruvate 1)muscle weakness molecules, and at the same time would gain ATP. However, 2)Seizures this is only a small portion of the produced ATP, the bulk of 3)Blindness the ATP does not produced there. Thus, during citric acid 4)degenerative illnesses associated with cycle which actually happens in the matrix of the aging mitochondrion, where bulk of NADH and FADH form in each → acts like a molecular clock cycle. These particular NADH and FADH will now be a fuel of → can be used to date ancient biological samples oxidative phosphorylation. From the raw from the refined by measuring the mutations that accumulate in the fuel that an energy will be produced. Starting from the mitochondrial DNA, researchers can assign an environment down to the different systems and now into its approximate age to the sequence. basic functional units, then down into its powerhouse or the mitochondria.  Mitochondrion: Parts 1. Smooth outer membrane  Glycolysis: Process 2. Intermembrane 3. Rough inner membrane 4. Cristae - crucial electron transport proteins 5. Matrix  - Splits glucose into 2 pyruvate Molecules - 1C was lost as Isocitrate - Each pyruvate molecule contains 3 carbon molecules becomes α-ketoglutarate - Yields ONLY 2 molecules of ATP (1 NADH) - Sufficient in fueling single celled - 1C was lost as α- Organisms ketoglutarate becomes ►when there is the presence of glucose in the cytosol, it Succinyl CoA (1 NADH) would be acted upon many enzymes, and will undergo - Succinyl CoA Succinate chemical processes which in turn would yield three (1 ATP) and as it cycled carbon pyruvates. In the process, 2 NAD+ will become 2 to become fumarate NADH, and 2 ADP will be added with 2 molecules of FADH2 was formed phosphate, and will yield 2 molecules of ATP. And this can be done in 10 separate steps. Basically, glycolysis will split glucose into 2 pyruvate molecules, then ech pyruvate molecules will contain 3 carbon molecules, and each turn of glycolysis will yield 2 molecules of ATP.this ►the isocitrate will become the alpha-ketoglutarate with is just sufficient in fueling sing-celled organisms, but not isocitrate giving off 1 carbon, as a byproduct it would for multicellular organisms. This is when citric acid cycle produce CO2. NAD+ ill become NADH. alpha- will begin. ketoglutarate is already a 5-C from being a 6-C isocitrate. ►glycolysis is considered to be the most ancient form of And then these alpha-ketoglutarate will now be energy production in a form of ATP. converted into succinyl CoA upon addition of coenzyme A again. And then during this process, 1 carbon will be  Citric Acid Cycle: the Process given off and NAD will be converted into NADH, there will a byproduct carbon dioxide. Now, we have succinyl CoA, a 4-carbon molecule, after this is produced, - 3C pyruvate will be Coenzyme A will again go out of the cycle. succinyl CoA converted to 2C will become succinate, with the addition of H2O. within acetic acid this process, GDP will be added with 1 molecule of - Acetic acid combines phosphate, which becomes GTP. These GTP can be with Coenzyme A (CoA) to actually converted into ATP. So succinate will undergo a form acetyl-CoA process to become yet another important molecule, - Acetyl-CoA will enter the where FAD will become FADH 2, and result to fumerate, cycle and enters a seat a 4-crbon molecule. The fumerate upon addition of H2O already occupied with will become malate (4C molecule), and malate will then Oxaloacetic acid become oxaloacetate, which is one of the ingredients for the first step of this cycle. During the process of malate becoming oxaloacetate, NAD will be converted into NADH. Then, the process will begin again. 1 pyruvate molecule will be acted upon by some enzymes to become acetic acid and then that acid will combine with Coenzyme A, and the process will begin again ► In the citric acid cycle, the 3 carbon pyruvate that - Fumarate become broken down during the glycolysis, they can be used as Malate which yield 1 raw material for the citric acid cycle. The 3 C pyruvate NADH before would be broken down and give off 1 carbon atom returning to the first together with the production of carbon dioxide. In turn, enzyme in the the breakdown would create a NADH from NAD with the process addition of hydrogen. Next, the 3C pyruvate would Oxaloacetate become 2 carboned acitic acid. These 2 carbon acitic acid will be joined by an enzyme called Coenzyme A. when this coenzyme A when added the 2 carbon acitic acid will become 2 carbon Acetyl CoA. Once the 2 carbon acetyl-coa join 4-carbon oxaloacetate, with the addition of hydrogen, this would result to citrate. Automatically, Coenzyme A would go out of this cycle. Now, the oxaloacetate will foresee with a 4-carbons, 2 carbon from the acitic acid will become the molecule citrate(6 carboned). citrate, upon another turn of events, will become isocitrate. ►in every turn of the wheel, there will be 1 pyruvate/ acitic acid to be added into the cycle. 1 glucose molecule would make 2 pyruvate molecules. Meaning, in 1 cycle, there will be 1 ATP produced. And since 1 glucose is capable of 2 cycles due to the 2 pyruvate that it can produce, 2 pyruvates can result to 2 ATPs. This is when succinal CoA become succinate. However, the ATP produced in the citric cycle is not enough to fuel a multicellular organism. But, the particular molecules produced (NADH, FADH), they can be used as a fuel to make the bulk of ATPs.  Electron transport system and Chemiosmosis ► In the cytosol, during the process of glycolysis, there are 2 ATPs which were produced out of 2 pyruvate molecules from 1 glucose. And then, these2 pyruvate molecules will become a raw fuel for the acid c ycle. Definitely, pyruvate becoming acetate would yield 2 NADH, as well as in glycolysis having 2 NADH. And then in the Kreb cycle, it would still yield 2 ATP ► the high energy electrons extracted from hydrogens molecules and in addition we have 6 NADH and 2 FADH, in the NADH and FADH will be transferred from one which are very rich in hydrogen molecules. These electron-carrier molecule to another. NADH will give off hydrogen atoms is very important in chemiosmossis or hydrogen, NADH will become NAD, together with FAD, the production of ATP by the ATP synthase. And so, they will go back to the Kreb cycle to pick up more these FADH and NADH which were actually produced hydrogen atoms. Now, the high energy electrons fall to a during the glycolysis and Kreb acid cycle, would actually successively low energy levels as they are transferred yield 2 FADH2, 10 NADH. Once they are fueled to the from one carrier through the electron-transport system. electron transport system, 2 molecules of FADH From complex 1 to complex 2. The electrons are passed multiplied by 1.5 ATP per FADH will become 3 ATPs. 10 to the oxygen, which serve as the final electron acceptor molecules of NADH multiplied by 2.5 ATP per NADH will of the electron transport system. Then, these oxygen, become 25 ATPs. Overall, 1 molecule of glucose would which are now negatively charged because it has generate 32 AT molecules. 28 of the 32 ATPs were acquired additional electrons, will combine with the actually generated in the inner membrane of the hydrogen ions which are positively charge due to mitochondria. In the cytosol, 2 ATPs and 2 NADH are donating electrons at the beginning of the electron produced via glycolysis. In the mitochondrial matrix, only transport system to form water. (5) As electrons move 2 NADH, 6 NADH, 2 FADH, and 2 ATp are produced. from the electron transport system, they release free But here in the mitochondrial inner membrane, the rest energies. So part of the released energy is lost as of the NADH and FADH were actually being utilized in heat,but some are harness by the mitochondrion to the electron transport chain reaction, so therefore, yields transport hydrogen across the inner mitochondrion via chemiosmosis 25 ATPs. membrane from the matrix, to the enter membrane space at the complexes 1, 2, 3, & 4. As a result, hydrogen ions are more heavily concentrated in the inter-membrane. And these hydrogen gradient supplies the energy that drives ATP synthesis by ATP synthase. And because of this gradient, the hydrogen ions have a strong tendency to flow into the matrix across the inner membrane via channels between the basal units and stators of these complexes. That’s why the flow of hydrogen ions activates the ATP synthase, and powers ATP synthesis by the headpiece, or the process chemiosmosis. The passage of hydrogen ions through the channels make the headpiece spin like a top. And as a result of the changes in its shape and position as it turns, the headpiece picks up ADP and phosphate, combining them. And in return, it releases ATP as a product.   Oxygen deficiency and anaerobic reactions  Ascorbate  Tocopherols  Flavonoids  Carotenoids  Uric acid  Mitochondrial Leakage of ROS ► Anaerobic conditions Glucose will become 2 molecules of pyruvate, at the same time, this is the process of glycolysis. And then only 2 ATPs will be produced. And pyruvate will not be available for the acid Kreb cycle, because there is no available oxygen. Then, in the process, pyruvate will become lactate. Once lactate accumulates, it will make the normal pH of the body more acidic or lower. ►Aerobic conditions Glucose will undergo the process of glycolysis will yield 2 molecules of ATPs, and then will become pyruvate, and the pyruvate will be subjected to the Kreb  Physiological uses of ROS cycle, and in this cycle, other molecules like ATPs, - Use by phagocytic cells as host defense NADH, and FADH will now be subject for electron mechanism to combat infection transport system and then the hydrogen molecules yield - Cytosolic ROS production under conditions of from the electron transport system wil now become the metabolic stress may trigger specific signaling one who’ll turn the wheel for the ATp synthase, and in pathways within the cell, activating mechanisms to return, the ATP synthase would make more ATPs, 28 cope with stress ATPs to be exact. Also, not just the production of 30 ATPs , but also the prodcution of CO2, Hydrogen, or  Phosphagens as source of ATP water as the byproduct. ► Phosphagens - are organic phosphate compounds present in high  Mitochondrial metabolism and oxidative concentrations in the muscle cell that can transfer a stress high-energy phosphate group to ADP in order to  Reactive Oxygen Species (ROS) regenerate ATP - electrons which leaked from mitochondrial - High in white muscles metabolism - Low concentrations in: - metabolites of molecular oxygen  red skeletal muscles - can potentially damage the tissues of host  Heart animals and contribute to aging process - Encompass a variety of diverse chemicals  Brain (superoxide anions, hydroxyl radicals, - Creatine phosphate in vertebrates peroxynitrite, and hydrogen peroxide) - Arginine phosphate in non-vertebrates - Some ROS are:  Free radicals (molecules containing one  What happened to cell if oxygen is limited? or more unpaired electrons and thus - Glycolysis becomes the primary pathway of ATP react readily with other molecules) replenishment.  Extremely unstable (hydroxyl radicals and superoxide)  Long-lived (hydrogen peroxide) - Lactate thus steadily accumulates in the tissues and - The body has an elaborate antioxidant gradually reduces the pH. system that counter ROS production:  Enzymatic scavengers  superoxide dismutase (SOD)  Catalase  glutathione peroxidase - Superoxide dismutase – increases the conversion of superoxide to hydrogen peroxide  Catalase  Glutathione peroxidase - Other nonenzymatic, low-molecular-weight molecules which are important in scavenging ROS:  Vaults  Cytoskeleton - three times as large as ribosomes - a complex protein network that acts as the “bone and - are shaped like octagonal barrels muscle” of the cell - intracellular scaffolding to support and organize the cell components into an appropriate arrangement and to control their movements - Provides: 1)distinct shape 2)size 3)complexity 4)intracellular specialization of the various body cells - cellular trucks which carries mRNA’s and ribosomes - 3 distinct elements: from the nuclear pore to the cytoplasm (1) microtubules, (2) microfilaments, and  Electron Micrograph of Vaults (3) intermediate filaments - different parts of the cytoskeleton are structurally linked and functionally coordinated to provide certain integrated functions for the cell  Microtubules - essential for maintaining asymmetric cell shapes and are important in complex cell movements - the largest of the cytoskeletal  Cytosol elements. -Occupies about 55% of total cell volume - very slender (22 nanometer, or nm, in - Semiliquid portion of the cytoplasm the surrounds the diameter, long, hollow, unbranched organelles tubes - Important in: - composed primarily of tubulin, a small, 1)intermediary metabolism; globular protein molecule (6 nm in 2)ribosomal protein synthesis; diameter) 3)storage of fat and glycogen; and 4)temporary storage of vesicles - position many of the cytoplasmic organelles, such as: 1)ER  Cytosol as storage 2)Golgi complex 3)Lysosomes 4)Mitochondria - essential for maintaining an asymmetric cell shape (intermediate filaments) - play an important role in coordinating numerous complex cell movements  Microtubules: coordinates cell movements (1) transport of secretory vesicles from one region of the cell to another, (2) movement of specialized cell projections such as  Centrosome, Centrioles, and Microtubule Organization cilia and flagella, and (3) distribution of chromosomes during cell division through formation of a mitotic spindle  transport of secretory vesicles - Provides a highway of molecular traffic in large long cells like neuron and tall thin epithelial cells with a driving force dependent on ATP.  - Molecular motors (kinesin)- transporters  Internal structure of cilia and flagella ►Molecular motors (dynein)-accessory protein  Movement of Flagella & Cilia - Cilia and Flagella- specialized protrusions from  Formation of mitotic spindle the cell surface which allow a cell to move materials across its surface or to propel itself through its environment ►Cilia (meaning “eyelashes”; singular, cilium) are numerous tiny, hairlike protrusions found in large numbers on the surface of a ciliated cell.  Microfilaments ►Flagella (meaning “whips”; - the smallest (6 nm diameter) elements singular, flagellum) are whip-like of the cytoskeleton visible with a appendages; typically, a cell conventional electron microscope has one or a few flagella at - Most common microfilaments: Actin most. ► Actin & Myosin  Microfilaments: Functions 1. They play a vital role in various cellular contractile systems, and 2. they act as mechanical stiffeners for several specific cellular projections.  Microfilaments: play a vital role in various cellular contractile systems 1. Muscle contraction 2. Cell division 3. Cell locomotion  ►Muscle Contraction  Intermediate Filaments: Functions 1)maintaining the structural integrity of a cell 2)resisting mechanical stresses externally applied to a cell  Intermediate Filaments: Examples 1)Neurofilaments in nerve cell 2)Intermediate filaments in muscle 3)Keratin in skin  Intermediate Filaments: Cell Composition 1) 85% of total protein in nerve cell and keratin-producing skin cells ► Cell Division  The cytoskeleton functions as as integrated whole, links other parts of the cell, and contributes to cytosolic “crowding” -The crowded cytosol. Diagram of cell interior with microtubules (light blue), actin filaments (dark blue), ► Cell Locomotion ribosomes (orange - WBC and purple), soluble - Fibroblasts proteins (light blue), - Skin cells kinesin (red), small - Sperm molecules (white) and RNA (pink). VPhy 101: Veterinary Physiology Cells: How They Communicate  Microfilaments: mechanical stiffeners for several  Cell-to-Cell Adhesions specific cellular projections - helps the cell in maintaining their integrity amidst movement of the body - Cells are adhered together in 3 diff. means: 1. Cell adhesion molecules (CAMs) - helps in th adhesion of the cells in a particular tissue 2) Extracellular matrix - serves as biological “glue” - an intricate meshwork of fibrous proteins embedded in a watery, gel-like substance composed of complex carbohydrates  Intermediate Filaments - The watery gel, an ECF component - intermediate in size between the microtubules and usually called the interstitial fluid, provides the microfilaments (7 to 11 nm in) a pathway for diffusion of nutrients, - The proteins that compose the intermediate wastes, and other water-soluble traffic filaments vary between cell types, but in general between the blood and tissue cells. they appear as irregular, threadlike molecules - Interwoven within this gel are three - Highly stable major types of protein fibers which gives the ECF the ability to get hold of the cell submerge into it : 1. Collagen 2. Elastin 3. Fibronectin 3) Specialized cell junctions - Three types of specialized cell junctions:  Cell Signaling a) desmosomes (adhering junctions), - the capability of a cell or group of cells to send - located in between 2 signals to a neighboring cell, distant cell, a very far interacting plasma membrane away or particular cells, in return, those cells will be - adhere one cell to another sent signals to would react to the signals which - has cadherins are inter-cellular were sent by the cell no.1. filaments which is responsible of - not only in neighboring cells, but also those far binding 2 different cells away cells, and how they will able to communicate - also has keratin which is or react with each other, it is due to the presence of inside cell-signal system in each cell of the body - there are certain signals that a cell is capable of reacting to, as well particular signals that a cell should send of for another cell or part of a organism to react to. “When things change, the cell will respond.” b) tight junctions (impermeable junctions), - in each change that a cell either internally or externally - located in between the cells detects, it has the capability t respond. It s their basic lateral membrane function of a cell, capacity to react to any stimulus. - there are strands junctional Example, person which are very outspoken or sensitive, proteins in a viral posts for example, those people who are open - also have kiss sites, and inter- a lot to their thoughts, the audience would react. cellular space - not allow passage of ions and  Four forms of intercellular signaling chemicals, important in not 1. Contact-dependent letting undigested enzymes and - must ave contact in between 2 cells in undigested food to pass order to react between the junctions of the 2. Paracrine cells. - its sending a stimulus coming from the environment (histamine) 3. Synaptic - the substances or neurotransmitter send of vi the synapses, located at the end of every axon of a neuron 4. Endocrine - involves the endocrine organs or cells. (ex.: parathyroid, thyroid, pituitary, adrenal gland, etc.) these hormones will be released by the endocrine cells, and will reach the area of interest or target cells via the blood. c) gap junctions (communicating “Each cell is programmed to respond to specific junctions combinations of extracellular signals” - these are the communicating aspect of a cell to cell - each cell of the body has the same different genetic relationship makeup or DNA blueprint.but, even though they are - presence of protein called made up of the same DNA, they are expressing a Connexon, which adhere with different gene at a time, making different proteins, doing each other to form gap junctions other function from each other. Because of thi, a allowing the passage of ions and particular cell, or two different cell which actually receive small molecules (1.5nm) the same signal or stimulus would act the same - if large molecules pass through, stimulus coming from another cell would react differently. it will be repelled due to its large - once a cell is a part of a tissue, those cells will have molecules the same function enabling them to aggregate with each - only capable of letting the other. passage of ions and small  Acetylcholine molecules 1. Heart pacemaker - adhered of one cytosol to - lessen the heartbeat another 2. Salivary gland cell - release of saliva 3. Skeletal muscle cell - trigger the phenomenon of contraction  - has both the receptors in the heart, salivary  Ca2+- water soluble gland, and skeletal muscles. But, the  Diacylglycerol(DAG)-lipid soluble neurotransmitter acethylcholine would induce different reactions, effect or signaling pathway in these particular cells. These cells have the same genetic blueprint, but due to their different reactions to a particular stimulus, they react differently. Although, they are reacting to the same ligand or substance. Same with the reaction of different organs to drugs given during medication, this is because these cells are programmed for different specific combinations of extracellular signals to respond. “There are three major classes of cell-surface receptor proteins” - these are made up of proteins, and these classes of cell-surface receptors are capable of receiving stimulus or signal coming from another cell or coming from the environment. These are the receiver of a particular signal.  Three classes of cell-surface receptor 1. Ion-channel coupled receptor - sensitive to the presence of ions 2. G-protein coupled receptor - this comprises most of the receptors present in the animal cell 3. Enzyme-coupled receptor  Intracellular signaling molecules are molecular  Cell surface receptors can be divided into switches (molecular switches) categories ► pass the signal on by binding to and altering the behavior of selected signaling or effector proteins. - “molecule switch”. they would pass the signal on” the signal coming from the messenger which is actually the stimulus, or ligand, a pracrine, hormone, or a neurotransmitter, that signal then coming from another cell in a form of a neurotransmitter, paracrine, or hormone signals will send signals to the receptors. And, in a way, the intracellular signaling molecules or the second messengers, they would pass the signal on by binding to and altering the behavior “Cell-surface receptors relay signals via intracellular of selected signaling or effector proteins. The signaling molecules” way to do that is via 2 ways, with the help of phosphate. These are: - these intracelllar signaling molecules are the ones that  Phosphorylation are located inside of the cell  GTP-binding proteins - a particular stimulus coming from either a paracrine cell or from the neuron or from endocrine gland, would ► Phosphorylation actually reach a receptor. So the receptor would serve Activator: as a receiver.