Cell Transport and Signaling

Plasma Membrane

-supporting the cytoplasm and organelles and for selective permeability

Cytosol

-Where organelles, molecules, and ions are suspended that help in the processes of the cell.

-metabolism, protein synthesis (free ribosomes)

-fluid compartment of the cell

Cytoskeleton

-cell shape and movement, intracellular transport

-microtubules, microfilament, actin, myosin

• for motility and structural support

Lysosome

-Detoxification

-intracellular degradation

-anything that needs to be broken down

Endosome

-cellular uptake of cholesterol, removal of receptors from the plasma membrane, uptake molecules and water into the cell, internalization of large particles (bacteria, cell debris)

-endocytosis (uptake)

Golgi apparatus

Modification, sorting, and packaging of proteins and lipids for delivery to other organelles within the cell or for secretion out of the cell

Proteosome

-degradation of intracellular proteins

Peroxisome

-detoxification of substance

Mitochondria

-Powerhouse of the cell, where ATP synthesis occurs

-ATP synthesis by oxidative phosphorylation, Ca2+ storage

-calcium for production of ATP

Endoplasmic Reticulum

-similar to maze: If a molecule needs to be transported from the nucleus to outside the cell, it will pass through the ER for processing. If it requires breakdown, it will go to the lysosomes before it exits the cell.

Rough ER

-protein synthesis

-translation of mRNA into membrane associated proteins or for secretion out of the cell

Smooth ER

-lipid synthesis, Ca2+ storage

Free ribosomes

-translation of mRNA into cytosolic proteins

Nucleus

-house the genetic material

-genome (22 autosomes and 2 sex chromosomes), DNA and RNA synthesis

Nuclear Membrane

-surrounds the nucleus; functions as a barrier to protect the nucleus and genetic material inside the nucleus.

All human cells have NM except

-Mature human red blood cells

-Cells within thelens of the eye

-Selective Transport

-Cell Recognition

-Tissue Organization: many plasma membrane =

many cells = formation of tissue

-Membrane-Dependent enzymatic activity:

-Determination of Cell Shape: serves as barrier

Functions of Plasma Membrane

Selective Transport

selective permeability through lipid bilayer of plasma membrane; it permits passage of some molecules while it hinders passage of some substances.

Cell Recognition

membrane proteins such as glycoproteins (ex. RBC membrane has specific glycoprotein depending on blood type)

Membrane-Dependent enzymatic activity

integral proteins; enzymes are types of proteins; depends on protein to determine the enzymatic activity

Phospholipids (major lipid)

Phosphoglycerides

Major lipids of the plasma membrane

Phosphoglycerides

With glycerol (-OH end)

Phospholipids

-Lipid with a phosphate end

-Amphipathic molecules that contain a charged (or polar) hydrophilic head and two hydrophobic fatty acyl chains

Amphiphatic nature

Phospholipids

-critical for the formation of the bilayer

Hydrophobic fatty acyl chains

Phospholipids

-resists water; forms the core of the bilayer

Polar/Hydrophilic head groups

Phospholipids

-water-loving; exposed on the surface

Kink/ Kinking

Phospholipids

-increases membrane fluidity; due to presence of double bonds

• Fluidity - kaya nakakapag-adjust si plasma membrane based on the environment.

• Double bonds - naiiba yung structure kaya nagkakaroon ng kinking

Majority have a glycerol “backbone”

Phospholipids

-Where the fatty acyl chains attach

-Alcohol (choline, ethanolamine, serine,

inositol, glycerol) is linked to glycerol via a phosphate group.

Phosphatidylcholine (lecithin)

Sphingomyelin

Phosphatidylserine amino phospholipids

Phosphatidylethanolamine

Major Phospholipids

Phosphatidylglycerol

phosphatidylinositol

cardiolipin

Other Phospholipids

True

The phospholipid composition of the membrane varies among different cell types and even between the bilayer leaflets.

Sphingomyelin

-has a sphingoside backbone instead of glycerol

True

Depending on the type of cell, nagkakaroon ng variations in the membrane proteins.

• Example: RBC (Figure 1.2)

• Not all cells have these components (kaya sya nagiging function as markers for cell-to-cell recognition & communication)

Cholesterol

-Sterol molecule that is also a critical component (50%) of the bilayer (Figure 1.3).

-Functions as a "fluidity buffer”, tends to keep the membrane fluidity in an intermediate range

-Found in both leaflets of the membrane

-Stabilize the membrane at normal body temp (37 C)

-Has an alcohol group combined to the fatty acid chain.

• Kasama siya sa components ng plasma membrane pero and main components ay phospholipids at phosphoglycerides.

Glycolipids

-Minor lipid component; less abundant

-Sugar attached to fatty acid chain

-2 fatty acyl chains linked to polar head groups consisting of carbohydrates

Important functions:

• Serves as receptor

• Antigen

Glycosylphosphatylinositol (GPI)

-important role in anchoring proteins to the outer leaflet of the membrane

-Also amphiphatic (like cholesterol & phospholipids); oriented with their polar groups on the outer surface of the leaflet (hydrophobic part = interior of bilayer)

Characteristics of Plasma Membrane

1. The lipid bilayer is NOT static

• Hindi constant/consistent ang location with other cells kasi nag-aadjust siya based on the environment

2. Fluidity - determined by temperature & lipid composition

• Increased temp = Increased fluidity (dissolves)

• Presence of unsaturated fatty acyl chains in phospholipids & glycolipids also increases membrane fluidity.

• Kink (on fatty acid tail) - determines fluidity of plasma membrane

3. Constrained or limited - movement of proteins in the membrane due to the junctional complexes (e.g., tight junctions)

• Gumagalaw siya pero limited

• Junctional complexes

• Vectorial transport

Junctional complexes

-separates the plasma membrane of epithelial cells into 2 domains: apical and basolateral

• Apical -main side exposed to the environment

  • Ex: sa airways, sila yung exposed sa air

  • Ex: sa genitourinary tract, yung mga tubules ang exposed sa tubular proteins

• Basolateral - anchored to the membrane

Vectorial transport

-transport of substances through the membrane with the use of specific integral proteins.

• Yung transport ng substances from one side to the opposite side ng plasma membrane through integral proteins.

integral

lipid-anchored

peripheral

Membrane Proteins classification

integral

peripheral

Membrane Proteins major types

Integral / Intrinsic Membrane Proteins

-Embedded/Integrated in the lipid bilayer

Transmembrane proteins -proteins that span the bilayer

• Hydrophobic region —> alpha helix; spans the membrane

• Hydrophilic amino acid residues - exposed to aqueous environment on either side of the membrane

-Serves as the passageway or channel for the important big molecules that cannot pass through the semi-permeable layer

-Examples of integral protein:

Integral protein

-Can be gated or non-gated.

• Gated

• Ligand

Gated

requires hormone or enzyme to activate

Ligand

-attachment lang para pumasok ang kailangan ng cell (ex: insulin)

Lipid-anchored Membrane Proteins

-Protein is covalently attached to a lipid molecule, which is then embedded in one leaflet of the bilayer.

• Glycosylphosphatidylinositol (GPI) —> anchors proteins to the outer leaflet

Peripheral / Extrinsic Membrane Proteins

-Associated with the polar head groups of the membrane lipids

-More commonly binds to integral or lipid-anchored proteins.

-For recognition, communication, etc.

-Found on the surface

Glycocalyx

-Combination of the outer leaflet lipids + proteins

-Exposed on the outer surface

-Glycosylated proteins

-For cell recognition (e.g., cell surface antigens) and formation of cell-to-cell interactions (e.g., attachment of neutrophils to vascular endothelial cells).

water channels

ion channels

solute carriers

adenosine triphosphate (ATP)-dependent transporters

-Membrane Transport Proteins

-Membrane transporters have been classified in different ways:

Specific (Plasma Membrane-Membrane Transport)

-expression of many other transporters in limited to specific cell types

Regulated (Plasma Membrane-Membrane Transport)

-altering the number of transporters in the membrane or altering the rate or kinetics of individual transporters

Water Channels

-AKA: Aquaporins (AQPs)

-Main routes for water movement into and out of the cell; widely distributed throughout the body (e.g., brain, kidneys, salivary glands, GI tract, and liver).

-Cells express AQP isoforms, and some even express multiple isoforms.

-All AQP isoforms allow passive movement of H2O across the membrane while some isoforms also provide pathways for other molecules such as glycerol, urea, mannitol, purines, pyrimidines, CO2, and NH3.

Ion Channels

Found in all cells, and are especially important for the function of excitable cells (e.g., neurons and muscle cells)

Selectivity

Channel Conductance

Gating

Classifications of Ion Channels

Selectivity

Ion chennels

Nature of ions to pass through the channel. Allow only specific ions

Channel Conductance

-Ion channels

-Refers to the number of ions that pass through the channel. Expressed in picosiemens (pS)

Gating

-ion channels

-May be controlled by membrane voltage, extracellular agonists or antagonists, intracellular messengers (e.g., Ca++, ATP, cyclic GMP), mechanical stretch of the plasma membrane

Solute Carriers

Represent a large group of membrane transporters

Uniporters (facilitated transporters)

-Transports a single molecule across the cell which is glucose or GLUT-1

Symporters (cotransporters)

-Moves two or more molecules/ions across the membrane. Na+/K+/2Cl- (NKCC)

Antiporters (exchange transporters)

Moves two or more molecules across the membrane in opposite directions. Na+/H+

Adenosine Triphosphate-Dependent Transporters

As their name implies, use the energy of ATP to drive the movement.

ATPase Ion Transporters

ATP-binding cassette (ABC) Transporters

Adenosine Triphosphate-Dependent Transporters classifications

ATP-binding cassette (ABC) Transporters

Have amino acid domains that bind ATP.

ATPase Ion Transporters

• V-type ATPases (vacuole type)

Found in the membranes of several intracellular organelles (e.g., endosomes, lysosomes) (H+-ATPase)

ATPase Ion Transporters

• P-type ATPases

phosphorylated during the transport cycle (Na+/K+-ATPase)

Vesicular Transport

Solute and water can be brought into the cell through a process of endocytosis and released from the cell through the process of exocytosis. In some cells, endocytosis across one membrane of the cell is followed by exocytosis across the opposite membrane. This allows the transport of substance inside the vesicles across the epithelium, a process termed transcytosis.

Pinocytosis

Phagocytosis

Opsonization

Endocytosis Types

Pinocytosis

-consists of nonspecific uptake of small molecules and water into the cell.

-Prominent feature of the endothelial cells that line capillaries (eg. alveoli, capillaries)

-Responsible for a portion of the fluid

exchange that occurs across these vessels

Phagocytosis

-allows for the cellular internalization of large particles (e.g., bacteria, cell debris)

-Important characteristics of cells in the immune system (neutrophils and macrophages)

-Often, but not always, it is a receptor-mediated process (opsonization).

Opsonization

-a process in the immune system where foreign particles, like bacteria or viruses, are coated with proteins called opsonins, making them more easily recognized and engulfed by phagocytes (Concept of vaccines, coating the protein with antibodies).

Receptor-mediated Endocytosis

allows uptake of specific molecules into the cell. Molecules bind to receptors on the surface of the cell

Exocytosis Types

Constitutive Secretion

Regulated Secretion

Regulated Secretion

-Occurs in endocrine cells, neurons, and exocrine glandular cells (e.g., pancreatic acinar cells).

-Storage of secretory product in the cytoplasm in secretory granules until an appropriate signal for secretion is received

- Mediated by accessory proteins SNARE (soluble N-ethylmaleimide sensitive fusion protein [NSF] attachment protein receptors) proteins

-Process of secretion is usually triggered by an increase in the concentration of intracellular Ca++

Transcytosis

Nag traverse, dinaanan niya lahat. Nag traverse siya sa cell. Cytosis movement. Nagkaroon siya ng cycle ng exocytosis at endocytosis.

Solute and Water Transport

The presence of a pathway is not sufficient for transport to occur; and appropriate driving force is also required.

Diffusion

The process by which molecules move spontaneously from an area of high concentration to one of low concentration.

• Fick’s first law of diffusion

Fick’s first law of diffusion

-Rate of diffusion will be faster for small molecules than for large molecules.

-Gas exchange in the lungs

-Movement of molecules through the cytoplasm of the cell

-Movement of molecules between cells in the extracellular fluid

• E.g. physiological responses of skeletal muscle to exercise is the recruitment or opening of capillaries that are not perfused at rest

Electrochemical Gradient

-AKA: Electro-chemical potential difference

-Quantitate the driving force acting on a molecule to cause it to move across a membrane

Constitutive Secretion

Occurs in plasma cells that are secreting immunoglobulin or in fibroblasts secreting collagen.

Passive Transport

-When the net movement of a molecule across a membrane occurs in the direction predicted by the electrochemical gradient

-AKA: Downhill transport or transport with the electrochemical gradient

Active Transport

-When the movement is opposite direction predicted by the electrochemical gradient

-Requires the input of energy (ATP)

-AKA: Uphill transport or transport against the electrochemical gradient

Primary active transport

transport is directly coupled to the hydrolysis of ATP Na+,K+-ATPase, H+-ATPase, or ABC transporters

Secondary active transport

use of the energy in the electrochemical gradient of the other molecule or molecules

Osmosis

-The movement of water across cell membranes movement of water is passive, with the driving force for this movement being the osmotic pressure difference across the cell membrane

• since passive, the movement is dependent on concentration gradient. Kung saan mataas si osmolarity, don ang flow ng water.

Osmotic pressure

-is determined by the number of solute molecules dissolved in the solution; measured in atmospheres (atm) calculated by van’t Hoff’s law:

• temperature can change; van’t Hoff’s law implies that the higher concentration, the higher osmotic pressure is.

Osmolarity

-Osmotic pressure generated by the dissolved solute molecules in 1 L of solvent (more applicable in solution)

-temperature dependent

-mmol/L number of particles mole

Osmolality

-molecules dissolved in 1 kg of solvent (usually water and/or bodily fluids; kaya mas gamit sa physiology concepts)

-Temperature independent

-Milliosmoles per kilogram of water

-Based on mass

Tonicity

-the effect of the solution on the volume of a cell

-Although related to osmolality, tonicity also accounts for the ability of the molecules in solution to cross the cell membrane

Isotonic

Solutions that do not change the volume of a cell are said to be

Hypotonic

causes a cell to swell/burst

Hypertonic

causes a cell to shrink

Effective osmoles

-are solutes that cannot freely cross cell membranes and therefore contribute to the osmotic pressure difference between compartments, causing water to move by osmosis, while being ineffective osmoles say otherwise

-Sodium is the best example of effective osmole kasi nasa isang compartment lang sya. Yung presence nya can contribute to osmotic pressure between two compartments and can trigger osmosis, so pedeng mag move yung water from inside to outside.

-On the other hand, yung urea is a solute that can cross cell membranes. So, di sya naggegenerate ng osmotic pressure, so consider it as an ineffective osmole.

Oncotic Pressure

-osmotic pressure generated by large molecules (especially proteins) in solution

-The higher concentration gradient, the higher osmotic pressure, the higher osmosis

-Due to the presence of proteins and its exerted osmotic pressure, oncotic pressure is more suitable for plasma proteins compared to van’t Hoff’s law.

HOMEOSTASIS : Body Fluid Compartments

-maintenance of constant volume and composition of the body fluid compartments (and their temperature in warm-blooded animals and humans).

-steady-state balance

“What goes IN, goes OUT or maintaining balance inside the body.”

0.6 / 60%

total body water (TBW) - Male

0.5 / 50%

total body water (TBW) - Female

Extracellula

Total Body Water (TBW) is divided into TWO COMPARTMENTS

Intracellular TBW

-Water INSIDE the cell

-40% of the TOTAL BODY WATER (60%)

-refer to the diagram below

Extracellular TBW

-Water OUTSIDE the cell

-20% of the TOTAL BODY WATER (60%)

Further divided into TWO COMPARTMENTS:

• Interstitial or Intercellular Fluid -> ¾ or 75% of the Extracellular Fluid (ECF).

• Plasma or Intravascular compartment -> ¼ or 25% of the Extracellular Fluid (ECF).