Exam 1 Objectives - Cellular Physiology

How do endocytotic vesicles form:

1. Membrane properties are altered such that the portion of the membrane to which the ligand is bound retracts inward; 2. inner membrane contractile proteins cause the retracted portion of the membrane to close; a sufficient amt of intracellular calcium ions is necessary for the contractile process (requires ATP) 3. the closed segment of membrane breaks away from the cell surface, forming a clathrin-coated endocytotic vesicle in the cytoplasm 4. removal of clathrin coat by an uncoating ATPase (requires ATP) 5. uncoated endocytotic vesicles undergo fusion with lysosomes, which digest macromolecular ligands from endocytotic vesicle

Three major functions of the cell membrane

1. Selective permeability: barrier that regulates the ICF and low it to be maintained at a composition much different than ECF; it decides what comes in or out 2. Receptor site: houses specific membrane-receptors for blood-burned substances (ex hormones) and endogenous substances (ex histamines) 3. Cellular communication: nerve impulse conduction

Describe the process of facilitated diffusion with regard to: mechanism of membrane transport

A molecule that is either too big or too lipid-insoluble binds to an integral membrane protein (acting as a transport protein), binds to the binding site, which causes a conformational change in the protein. Non-covalent (electrostatic, hydrogen bonds) is the mechanism by which the substance binds to the binding site. The substance then passes through the channel and is released into the cell. A concentration gradient must exist. NO ENERGY REQUIRED

Define active transport

Active transport requires the input of energy (ATP) because a molecule is generally being transported against its concentration gradient. Conformational change will only take place if energy is added to the system.

Define properties of chemical specificity

Chemical specificity: glucose and galactose are both hexose monosaccharides and use the same transporter

Role of cholesterol in providing membrane fluidity; what factors increase or decrease fluidity

Cholesterol is an inflexible molecule and therefore causes decreased fluidity as its concentration increases. Temperature increase, decrease cholesterol, and increased unsaturation of fatty acid hydrocarbon tails increase fluidity

Explain the following properties of membrane carrier proteins: competitive inhibition

Competitive inhibition: competition from structurally related substances capable of interacting with the carrier protein; D-glucose and D-galactose exhibit competitive inhibition by competing for the same transporter binding sites

Define concentration gradient

Concentration gradient refers to the tendency for a substance to move from a region of higher concentration to a region of lower concentration.

Describe the process of facilitated diffusion with regard to: factors determining the rate of diffusion (conformational changes, carrier saturation, Vmax)

Conformational changes: Carrier saturation: when the concentration is so high that all binding sites are filled, maximal transport velocity (Vmax) is reached

Distinguish between cotransport and countertransport mechanisms and the direction of movement for sodium and transported substance.

Cotransport (symport): the transport of substances with sodium, in the same direction simultaneously The sodium/potassium pump creates and maintains a large concentration gradient of sodium extracellularly. Na-Glucose cotransport: in the intestinal tract, glucose enters with Na+; same thing in the lumen of the proximal tubule Countertransport (antiport): the transport of two substances in opposite directions

Peripheral proteins (location, function)

Don't extend into the lipid bilayer, located intracellularly or extracellularly bound to polar heads of membrane phospholipids or integral proteins. Functions: structural elements of intracellular cytoskeleton, intracellular molecular signaling processes

Compare and contrast the ECF and ICF with regard to: the differences in calcium ion concentrations; why is this difference critical?

ECF: 2.4 mEq/L ICF: 0.0001 mEq/L CRITICAL DIFFERENCE BECAUSE CALCIUM IS TOXIC TO CELLS

Compare and contrast the ECF and ICF with regard to: the pH

ECF: 7.4 (plasma) ICF: 7.0 (due to degradation of proteins

Compare and contrast the ECF and ICF with regard to: the principal cations and anions

ECF: Na+, Cl- ICF: K+, Mg2+, Phosphates (-) and proteins (-)

Integral proteins (location, function)

Embedded in the cell membrane and function as ion channels or pumps, carriers for transport processes, enzymes

Define endocytosis and its various roles

Endocytosis: the uptake and internalization of extracellular material and very large molecules by cells using mechanisms requiring energy input in the form of ATP Transport of very large molecules/complexes (vitamin B12/intrinsic factor) - phagocytosis Clearance of certain molecules or complexes from the ECF (ex LDL-C) - by receptor-mediated endocytosis

Define exocytosis and difference between regulated and constitutive exocytosis

Exocytosis: process for excreting molecules, stored in secretory vesicles (granules), from cells using the reverse process as for endocytosis, and requires ATP Regulated: extracellular stimulus causes fusion of vesicle with cell membrane and release of contents Constitutive: continuous release of material without an storage step, not requiring a signal

List the types of molecular species which exert osmotic activity.

Fluid exchange between the ECF and ICF compartments is regulated primarily by osmotic forces exerted across the membrane by small solutes, such as sodium and chloride ions, other electrolytes, and other water-soluble substances.

Where are carbohydrates associated with the cell membrane located?

Glycoproteins/glycolipids, located at outer membrane surface in contact with ECF

Where do regions of hydrophobicity and hydrophilicity face in relation to ICF/ECF

Heads face ECF and ICF (outer/inner surfaces of cell membrane) and are hydrophilic, polar/ionized. Tails face inward and face each other, hydrophobic

Bonding forces that stabilize the structure

Hydrophobic interactions (bonds between hydrocarbon tails), Van deer Waals forces (major attractive forces between the tails), hydrogen bonding (water, not strong alone), electrostatic forces. ALL are non-covalent forces

Explain how the concentration of impermeable solutes determines final cell volume when a cell is placed in a medium of differing tonicity

Initially, the cell will swell or shrink depending on the tonicity of the medium (swell if it is placed in a hypotonic solution, shrink if it is placed in a hypertonic solution). Any solutes that are permeable to the membrane will pass through and are equilibrated on both sides, removing any osmotic force that those solutes were initially exerting. The final osmotic forces are exerted by the solutes that are impermeable, and there the cell volume will be final.

Explain the relationship between molarity and osmolarity for both undissociated and ionized (dissociated) substances

Molarity will be the number of moles per liter of a substance for undissociated substances. Osmolarity will be the number of moles times the number of separate molecules into which the substance dissociates in water. If a substance doesn't dissociate, it's molarity and osmolarity will be equal.

Describe the process of facilitated diffusion with regard to: which molecular species require this transport process.

Molecules that are too big, too lipid-insoluble, or a mixture of both need facilitated diffusion to cross the cell membrane

Smooth endoplasmic reticulum (structure/role)

No ribosomes, have oxidizing enzymes that metabolize foreign chemicals (drugs) Role - synthesis of phospholipids and cholesterol, incorporated into vesicles which with GA

Define partition coefficient

Partition coefficint (Kp) is a rough measurement of lipid solubility that is estimated from the ratio of the concentration of n-octanol to the concentration in an aqueous buffer solution

Distinguish between the primary and secondary forms with regard to the source of energy.

Primary active transport: Na+-K+ pump - pumps three sodium cations out of cell in exchange for two sodium cations into the cell to maintain these two concentrations and a net negative resting potential and maintains cell volume Ca2+ pump (plasma membrane Ca ATPase): maintains ECF concentration at 10^4 times that in the ICF; controls resting state levels of Ca2+ ions in heart mus H+ pump: gastric parietal cells: HCl secretion; distal tubular and collecting duct cells: H+ secretion Secondary active transport: the gas inside the tank represents potential energy; similarly, there are processes in the body that help us build up a supply of potential energy (ex, Na-K ATPase, creates a permanent sodium gradient and maintains it by using ATP, and the concentration gradient represents potential energy). The energy for secondary active transport comes from another molecule going down its concentration gradient.

Define active transport

Primary: directly uses chemical energy (such as from adenosine triphosphate or ATP in case of cell membrane) to transport all species of solutes across a membrane against their concentration gradient. Secondary: cotransport/countertransport

The structural component present in the highest average amount (%)

Protein (55%), carbohydrates (3%), lipids (42%, majpr type is phospholipid 2-50%)

Cytoskeleton

Provides structural support for the cell membrane and other structures, includes: Filamentous proteins (contraction) - actin: elastic support for cell membrane, actomyosin: contractile mechanism Microtubules (ciliary motion, mitosis) formed from polymerization of tubulin

What is receptor-mediated endocytosis (RME)

RME is the specific uptake of a substance by the cell with plasma membrane surface receptors for that substance (ligand); ex hepatic uptake of low-density lipoproteins (LDL; bad cholesterol, large molecules, removed in liver) and some protein hormones

Rough endoplasmic reticulum (structure/role)

Ribosomes on surface where protein synthesis occurs; proteins go into endoplasmic matrix and then to GA. Role - protein synthesis

Define diffusion

Simple diffusion (active transport): Transcellular -permeation through the membrane at the apical/luminal cell surface; dissolution in and diffusion thru lipids of lipid bilayer or mvmt thru aqueous channels Paracellular - mvmt thru the junctions between adjacent cells

Peroxisomes

Small, membrane-bound organelle with many enclosed oxidizing enzymes Role - intracellular formation of hydrogen peroxide, used to oxidize other substances that might be harmful to the cell Role of catalase - reduces hydrogen to water

Be familiar with the examples of sodium cotransport for glucose and amino acids in the GI tract and kidney.

Sodium cotransport for glucose/amino acids in GI tract: five separate carriers (absorption from the small intestine (duodenal epithelium); reabsorption from the kidney (proximal tubule epithelium)

Describe the process of facilitated diffusion with regard to: steriospecificity

Steriospecificity: D-glucose and D-galactose are both substrates for the transporter, but L-glucose is transported at an extremely slow rat

Golgi apparatus

Structure: stacks of flattened membranous sacs (cisternae) Role - functions with ER to create molecule-filled lysosome and intracellular secretory vesicles (are stimulated by Ca2+ to fuse with cell membrane and release contents into extra cellular space arak exocytosis

Mitochondria

Structure: two lipid bi-layer protein membranes, outer membrane/outer chamber, inner membrane (i folding called cristae), contains enzymes/proteins of electron transport system Role - oxidative phosphorylation (process by which nutrients are oxidized to yield CO2/H2O while releasing large amounts of E/heat, E used to synthesize ATP Glucose broken down in glycolysis (6C -> 3C pyruvate) ETS: series of compounds that transfer e- from e- donors to e- acceptors via redox runs, and couples this e- transfer with the transfer of protons (H+) across a membrane creating an electrochemical gradient that drives ATP synthesis Oxidative phosphorylation: metabolic pathway in which the mitochondria in cells use their structure, enzymes, and E released by the oxidation of nutrients to reform ATP

Lysosomes

Structure: vesicles formed from GA Role - functions in intracellular digestion (damaged cell structure, products of dietary digestion, foreign matter) Digestive enzymes present include protease (turn proteins into AAs), amylase (turn carbohydrates to glucose), lipases (turn lipids to fatty acids)

Arrangement of the phospholipids in the lipid bilayer

Two layers of phospholipids with hydrophobic tails and hydrophilic heads. Also contain globular proteins that are integral or peripheral, water move easily through but large polar molecular cannot

Explain the operation of the Na-K ATPase and how it regulates cell volume.

Ultimate job is to push sodium out against its concentration gradient (and bring potassium inside) in order to maintain cell volume. It is a complex active transport mechanism. The Na-K ATPase (pump) has three binding sites for sodium on the intracellular side; 2 potassiums bind from the extracellular side. If sodium were to accumulate inside the cell, intracellular swelling would occur. (ATP is converted to ADP + Pi)

State the direction of water movement in terms of the water concentration and the solute concentration between fluid compartments separated by a semipermeable membrane.

Water moves in a direction from higher concentration to lower concentration, or toward the higher concentration of SOLUTE.

Are there any differences in the compositions of plasma and IF and why?

Yes; plasma and IF have the same ionic concentrations but different concentrations of plasma proteins (like albumin, whose molecular weight is so large it cannot move between gaps between endothelial cells under normal circumstances and remains in plasma).

Define osmotic pressure

amt of pressure required to stop the osmotic mvmt of water between two compartments; determined by the number of osmotically active particles in solution, regardless of molecular weight.

Define hyperosmotic

if solution A exerts a greater osmotic pressure than solution B, then it is hyperosmotic with respect to B

Define hypoosmotic

if solution A exerts a lesser osmotic pressure than solution B, then it is hyposmotic with respect to B

Transporting epithelia (transepithelial transport):

in: GI tract, renal tubules, exocrine glands, gall bladder, choroid plexus cells are polarized with respect to transport properties • brush borders (luminal surfaces) contain cotransport mechanisms • tight junctions between cells separate luminal and basolateral surfaces • primary active transport processes are contained on the basolateral surfaces • facilitated diffusion carriers located on basolateral surfaces

Describe the process of simple diffusion with regard to: principal factors determining the rate of diffusion (table in Notes): if you increase the...

membrane thickness - decreases rate lipid solubility - increases rate number of channels - increases rate temperature - increases rate molecular weight - decreases rate channel diameter - increases rate membrane area - increases rate

Compare and contrast the ECF and ICF with regard to: presence of proteins

much greater in the ICF

Describe the process of simple diffusion with regard to: transport of water-soluble substances

mvmt of charged species (ions) through specific membrane channels (INTEGRAL PROTEINS), also according to gradient, OR through membrane pores (water, uncharged water-soluble molecules that are relatively small)

Describe the process of simple diffusion with regard to: transport of lipid-soluble substances

mvmt of substance directly thru cell membrane according to its concentration gradient; must have sufficient lipid-solubility (determined by its partition coefficient - the higher, the more lipid soluble)

Define tonicity

osmotic pressure exerted by an aqueous medium affects the volume of cells Isotonic: concentrations are equal, no movement of water Hypertonic: higher solute conc. outside of the cell. Water moves out of the cell Hypotonic: lower solute conc. outside of the cell. Water moves into the cell.

Define osmolarity

the measure of solute concentration

Define osmosis

the net mvmt of water between compartments due to a concentration diff in water

Define crenation

the shrinking of cells when water exits after flowing down its concentration gradiet

Define lysis

the splitting of cell when so full of influxed water

Define hematocrit

the volume percentage of red blood cells in the blood

State the average volumes of the fluid compartments and the approximate amounts of total body water they represent

total body water: 42 L intracellular fluid (ICF): 28 L, or 67% total body water extracellular fluid (ECF): 14 L, or 33% total body water interstitial fluid (ISF, or IF): 11 L, or 26% total body water plasma: 3 L, or 7% total body water

Define isosmotic

two solutions exert identical osmotic pressures