The cell and its function

Cell is the basic unit of the body

Organization of the cell

Cell composition

• Water :70-85% , • Ions • Proteins: 10-20% , • Lipids : 2-95%• Carbohydrates : 1-6 %

1-Water:• The principal fluid medium of the cell• present in most cells except fat cell

2-protiens :• divided into two types : A- Structural proteins:Present in the cell mainly in the form of long filaments (mainly form microtubules that provide the cytoskeletons of such cellular organelles. b- functional proteins:Composed of combination of few molecules in tubular globular form (they are mainly the enzymes of the cell)

• Lipids:• Important lipids are : phospholipids and cholesterol

constitute only about 2% of the total cell mass, they are mainly insoluble in water and therefore are used to form the cell membrane and intracellular membrane barriers that separate the different cell compartments.

• Neutral fat (triglycerides): in fat cell triglycerides account for 95% of the cell mass.

• The fat stored in theses cells represent the body’s main storehouse of energy-giving nutrients

• Carbohydrates :• Little structural function in the cell and play a

major role in nutrition of the cell .• Most human cells do not maintain large stores

of carbohydrates , the amount usually averages about 1% of their total mass but increase to 3% in muscle cell and 6% in liver .

Membranous structure of the cell

• Cell membrane• Nuclear membrane • Membrane of the endoplasmic reticulum • Membrane of mitochondria, lysosomes and

Golgi apparatus.

Cell membrane

• Thin ,pliable , elastic structure

• 7.5 – 10 nanometers thick

• Mainly composed of proteins and lipids.

• Protein 55%• Phospholipids 25%

Cell Membrane Components:

• barrier to water and water-soluble substances• organized in a bilayer of phospholipid molecules

hydrophilic“head”

hydrophobicFA “tail”

ions H2Ourea

CO2

1 - LIPIDS:

O2N2

halothaneglucose

• provide “specificity” to a membrane• defined by mode of association with the lipid bilayer– integral: channels, pores, carriers, enzymes, receptor, etc.– peripheral: enzymes, intracellular signal mediators, controllers of transport of substances through pores

K+

2- Proteins:

• glycolipids (approximately 10%)• glycoproteins (majority of integral proteins)• proteoglycans (carbs bound to protein cores)• Glycocalyx loose carbohydrate coat outside surface of the cell

GLYCOCALYX

3 - Carbohydrates:

• important function for it:o negative charge of the carbo chains repels other o negative chargeso involved in cell-cell attachments/interactionso play a role in immune reactionso Act as receptor substance for binding hormone such

as insulin

GLYCOCALYX

(-)

(-)

(-)

(-)

(-)

(-)(-)

Carbohydrates (Cont.):

Cytoplasm and its organelles

• Cytosol :clear fluid portion of the cytoplasm in which the particles are dispersed in .

• Particles Dispersed in cytoplasm are :1- neutral fat globules 2-Glycogen granules 3-ribosomes 4-Secretory vesicles5- the other organelles

Cell Organelles

1 - The Endoplasmic Reticulum:• Network of tubular and flat vesicular structures• Membrane is similar to (and contiguous with) the plasma membrane • Space inside the tubules is called the endoplasmic matrix

• outer membrane surface covered with ribosomes

• newly synthesized proteins are extruded into the ER matrix

• proteins are “processed” inside the matrix - cross-linked - folded- glycosylated (N-linked)- cleaved

Rough or Granular ER

• Part of ER has no attached ribosomes.

• site of lipid synthesis -phospholipids - cholesterol

• growing ER membrane buds continuously forming transport vesicles, most of which migrate to the Golgi apparatus

Smooth ER (a Granular ER)

The Golgi Apparatus:

• Membrane composition similar to that of the smooth ER and plasma membrane• Composed of 4 or more stacked layers of flat vesicular Structures• This apparatus is

prominent in secretory cell, where its located on the side of the cell from which the secretory substance are extruded.

• Receives transport vesicles from smooth ER

• Substances formed in the ER are “processed”

- phosphorylated- glycosylated

• Substances are concentrated, sorted and packaged for secretion.•Transported substance are then processed in Golgi apparatus to form :- Lysosomes- Secretory vesicle- Cytoplasmic component

Lysosomes:

•Lysosome provide an intracellular digestive system that allows the cell to digest:-damaged cellular structure-food particles that have been ingested by cell -unwanted matter such as bacteria

• contain hydrolytic enzymes (acid hydrolases)- phosphatases- nucleases- proteases- lipid-degrading enzymes- lysozymes digest bacteria

• vesicular organelle formed from budding Golgi

• fuse with pinocytotic or phagocytotic vesicles to form digestive vesicles

Peroxisomes:

• similar physically to lysosomes

• two major differences:• formed by self-replication • they contain oxidases (hydrogen peroxide and catalase)

Function: oxidize substances (e.g. alcohol) that may be otherwise poisonous

Secretory Granules

Secretory vesicle in acinar cells of the pancreas

Secretion:

• secretory vesicles containing proteins synthesized in the RER bud from the Golgi apparatus

•These vesicle store protien proenzyme (enzymes that are not yet activated)

• fuse with plasma membrane to release contents

- constitutive secretion - happens randomly

- stimulated secretion - requires trigger

Secretory vesicles diffuse through the cytosol and fuse to the plasma membrane

Exocytosis:

Lysosomes fuse with internal endocytotic vesicles

Mitochondria (powerhouse) :

Primary function: extraction of energy from nutrients

Mitochondria are self-replicative

Matrix: contain large amount of dissolve enzymes

cytoskeleton

• Fibrillar protein originated as precursor protein molecules synthesized by ribosomes in the cytoplasm.

• The precursor molecules then polymerize to form filaments

• The primary function of microtubules is to act as cytoskeleton , providing rigid physical structure

The Nucleus: “Control Center” of the Cell

Nucleus contains large quantities of DNA ,which are the genes .

The Nucleus: “Control Center” of the Cell

• Nuclear membrane is two separated bilayer membrane, the outer membrane is continuous with the endoplasmic reticulum.

• Nuclear membrane penetrated by several thousand nuclear pores

• 100 nm in diameter

• functional diameter is ~9 nm

• (selectively) permeable to molecules of up to 44,000 MW

The nuclear membrane is permeated by thousands of nuclear pores

Chromatin (condensed DNA) is found in the nucleoplasmo Nucleolus• one or more per nucleus• contains RNA and proteins• not membrane delimited• functions to form the granular “subunits” of ribosomes

• molecules attach to

cell-surface receptors concentrated in clathrin-coated pits

• receptor binding induces invagination

• also ATP-dependent and involves recruitment of actin and myosin

Ingestion by the cell Receptor-mediated endocytosis:Pinocytosis and phagocytosis

Digestion of Substances in Pinocytotic or Phagocytic Vesicles

Pinocytosis : ingestion of minute particles that form vesicles of extracellular fluid in the cytoplasm

Digestion of Substances in Phagocytosis Phagocytic Vesicles

• Phagocytosis: the same as pinocytosis except that it involve large particles rather than molecule like macrophages and WBC.

• Phagocytosis occur in the following steps :

1- the cell membrane receptors attach to the surface ligands of the particles. 2- the edge of the membrane around the points of attachment evaginate outward within a fraction of a second to surround the entire particle, all this occurs suddenly in a zipper like manner to form a closed phagocytic vesicle. 3- action and other contractile fibrils in the cytoplasm surround the phagocytic vesicle and contract around its outer edge , pushing the vesicle to the interior. 4- the contractile proteins then pinch the stem of the vesicle so completely that the vesicle separates from the cell membrane , leaving the vesicle in the cell interior in the same way that pinocytosis vesicle are formed.

Digestion of pinocytosis and phagocytic foreign substance inside the cell

• Function of the lysosomes:-lysosome attached to the vesicle and empty their acid hydrolases to the inside of the vesicle -digestive vesicle is formed inside the cell cytoplasm and hydrolyzing just begin, the products of digestion are small molecules of amino acid , glucose, phosphate, then diffuse through membrane of the vesicle into the cytoplasm.Residual body is left from digestive vesicle which represent indigestible substances, and this is excreted by exocytosis.Digestive organ is Pinocytic and phagocytic vesicle containing lysosomes.

Regression of the tissue and autolysis of cells

• Tissue of the body often regress to a smaller size and the lysosomes are responsible for much of this regression

• Lysosomes also remove damaged cells (autolysis) or damaged portion of cells from tissues

• Lysosomes also contain bactericidal agents that can kill phagocytized bacteria before they can cause cellular damage.

-lysozyme: dissolve the bacterial cell membrane-Lysoferrin : bind iron and before they can promote bacterial

growth-acid at a PH 5 , which activate the hydrolase and inactivate

bacterial metabolic system.

Syntheses and formation of cellular structure by endoplasmic reticulum and

Golgi apparatus• Proteins are formed by the granular endoplasmic

reticulum within the structure of the ribosomes• Lipids are formed by the smooth endoplasmic

reticulum especially (phospholipids and cholesterol).

-this process cause the ER to grow more extensive and to keep it normal small vesicle called ER vesicles continually break away from the smooth reticulum and then migrate to Golgi apparatus.

Other function of the endoplasmic reticulum

• It provides the enzyme that control glycogen break down when glycogen is to be used for energy

• It provides a vast number of enzymes that are capable of detoxifying substances such as drugs .detoxification achieved by coagulation ,oxidation , hydrolysis , conjugation with glycoronic acid.

Specific function of the Golgi apparatus

• Synthetic function of the Golgi apparatus: 1-provide additional processing of substances already formed in the ER. 2-cabibility of synthesizing certain carbohydrates that cannot be formed in the ER .-especially the formation of large saccharide polymers bound with small amounts of protein (hyaluronic acid and chondroitin sulfate)

• A few of the many function of hyaluronic and chondroitin sulfate in the body are :

1-they are the major components of proteoglycans secreted in mucus and other glandular secretion.2- they are the major components of the ground substance outside the cells in the interstitial spaces acting as fillers between collagen fibers and cells 3- they are principal components of the organic matrix in both cartilage and bone4- they are important in many cell activities including migration and proliferation.

Step 1. • Carbohydrates are converted into glucose• Proteins are converted into amino acids • Fats are converted into fatty acids

Step 2. • Glucose, AA, and FA are processed into Acetyl-CoA

Step 3. • Acetyl-CoA reacts with O2 to produce ATP A maximum of 38 molecules of ATP

are formed per molecule of glucose degraded.

ATP production (function of the mitochondria)

Step 1. • glucose converted to pyruvic (glycolysis)amino acids and fatty acids and pyruvic acid converted into the compound acytel-Coa in the matrix of the mitochondrion

Citric acid cycle or Krebs cycle : chemical reaction in mitochondrion for further dissolution.In this cycle the acytel-Coa is split into hydrogen atoms and carbon dioxide

ATP production (function of the mitochondria)

The Use of ATP for Cellular Function

1. Membrane transport2. Synthesis of chemical

compounds3. Mechanical work

(muscle contraction, by ciliary and ameboid motion)

• ATP concentration is ~10x that of ADP

Locomotion of cell

1-ameboid movement2-cilia and ciliary movements (cilium and flagellum)

Ameboid movement

• It is the movement of an entire cell in relation to its surroundings.

• It begins with protrusion of pseudopodium from one end of the cell ,then projects far out from the cell body and partially secure itself in a new tissue area

• Then the remainder of the cell is pulled toward the pseudopodium.

Ameboid Locomotion:

• Mechanism is result from continual formation of new cell membrane at the leading edge of the pseudopodium and continual absorption of the membrane in mid and rear portion of the cell.

• continual endocytosis at the “tail "and exocytosis at the leading edge of the pseudopodium

• attachment of the pseudopodium is facilitated by receptor proteins carried by vesicles

• forward movement results through interaction of actin and myosin (ATP-dependent)

Ameboid locomotion

• Types of cells exhibits ameboid locomotion:1-WBCs2-fibroblast which move into damaged area3- its especially important in development of the embryo and fetus after fertilization of

an ovum.

chemotaxis is the most important initiator of ameboid locomotion by chemotactic substance

Cell movement is influenced by chemical substances…

high concentration(positive)

Low concentration(negative)

Chemotaxis

Cilia and Ciliary Movements:

• Each cilium is an outgrowth of the basal body and is covered by an outcropping of the plasma membrane.

• Occurs only on the inside surfaces of the human airway (cause a layer of mucus to move at a rate of about 1cm\min toward the pharynx) and fallopian tubes(to transport the ovum from ovary to uterus)

• Each cilium is comprised of 11 microtubules

• 9 double tubules• 2 single tubules

axoneme

• Ciliary movement is ATP-dependent (also requires Ca2+ and Mg2+)

Cilia and ciliary movementMechanism of ciliary movement:1-The 9 double tubules and the two single tubule are all linked to one another by a complex of protein cross-linkage this is called the axoneme2-after removal of membrane and destruction of other elements of the cilium ,the cilium can still beat under appropriate condition3-there are two necessary condition for continued beating of the axoneme after removal of the other structure of the cilium:A- the availability of the ATPB-appropriate ionic condition especially (Mg and Ca)4-during forward motion of the cilium the double tubules on the front edge of the cilium slide outward toward the tip of the cilium, while those on the back remain in place.5-multiple protein arms composed of the protein dynein ,which has ATPase enzymatic activity ,project from each double tubule toward an adjacent double tubule.

flagellum

• Is much longer than cilium and its moves in quasi-sinusoidal waves instead of whip like movements.

TRANSPORT ACROSS CELL MEMBRANES

1-simple diffusion 2-carrier mediated transport3-Facilated diffusion 4-primary active transport5-co transport6-counter transport

TRANSPORT ACROSS CELL MEMBRANES

• A. Simple diffusion 1. Characteristics of simple diffusion

■ is the only form of transport that is not carrier-mediated.

■ occurs down an electrochemical gradient (“downhill”). ■ does not require metabolic energy and therefore is passive.

J=-PA(C1-C2)

Permeability

• is the P in the equation for diffusion.• describes the ease with which a solute diffuses through a membrane.• depends on the characteristics of the solute and the membrane. A- Factors that increase permeability: • ↑ Oil/water partition coefficient of the solute increases

solubility in the lipid of the membrane.• ↓ Radius (size) of the solute increases the diffusion

coefficient and speed of diffusion. • ↓ Membrane thickness decreases the diffusion distance.

CARRIER MEDIATED TRANSPORT• includes facilitated diffusion and primary and secondary

active transport.• The characteristics of carrier-mediated transport are: 1. Stereospecificity For example, D-glucose (the natural isomer) is transported by facilitated diffusion, but the L-isomer is not. 2. Saturation :the transport rate increases as the concentration of the solute increases, until the carriers are saturated. 3. Competition. Structurally related solutes compete for transport sites on carrier molecules. ( galactose is a competitive inhibitor of glucose transport in the small intestine)

Facilitated diffusion Characteristics of facilitated diffusion :

■ occurs down an electrochemical gradient (“downhill”), similar to simple diffusion. ■ does not require metabolic energy and therefore is passive ■ is more rapid than simple diffusion. ■ is carrier-mediated and therefore exhibits Stereospecificity, saturation, and competition.

Example of facilitated diffusion ■ Glucose transport in muscle and adipose cells is “downhill,” is carrier-mediated, and is inhibited by sugars such as galactose; therefore, it is categorized as facilitated diffusion. In diabetes mellitus, glucose uptake by muscle and adipose cells is impaired because the carriers for facilitated diffusion of glucose require insulin.

Primary active transport

Characteristics of primary active transport: ■ occurs against an electrochemical gradient (“uphill”). ■ requires direct input of metabolic energy in the form of

adenosine triphosphate (ATP) and therefore is active. ■ is carrier-mediated and therefore exhibits stereo

specificity, saturation, and competition. Examples of primary active transport a. Na+,K+-ATPase (or Na+–K+ pump) in cell membranes

transports Na+ from intracellular to extracellular fluid and K+ from extracellular to intracellular fluid; it maintains low intracellular [Na+] and high intracellular [K+].

■ Both Na+ and K+ are transported against their electrochemical gradients. ■ Energy is provided from the terminal phosphate bond of ATP.

■ The usual stoichiometry is 3 Na+/2 K+. ■ Specific inhibitors of Na+,K+-ATPase are the cardiac glycoside

drugs ouabain and digitalis. b. Ca2+-ATPase (or Ca2+ pump) in the sarcoplasmic reticulum

(SR) or cell membranes transports Ca2+ against an electrochemical gradient.

■ Sarcoplasmic and endoplasmic reticulum Ca2+-ATPase is called SERCA.

c. H+,K+-ATPase (or proton pump) in gastric parietal cells transports H+ into the lumen of the stomach against its electrochemical gradient.

■ It is inhibited by proton pump inhibitors, such as omeprazole

SECONDARY ACTIVE TRANSPORTCharacteristics of secondary active transport :a. The transport of two or more solutes is coupled. b. One of the solutes (usually Na+) is transported “downhill” and provides energy for

the “uphill” transport of the other solute(s). c. Metabolic energy is not provided directly, but indirectly from the Na+ gradient that

is maintained across cell membranes.(Thus, inhibition of Na+,K+-ATPase will decrease transport of Na+ out of the cell, decrease the transmembrane Na+ gradient, and eventually inhibit secondary active transport).

d. If the solutes move in the same direction across the cell membrane, it is called co-transport, or symport.

(Examples are Na+–glucose cotransport in the small intestine and Na+–K+–2Cl– cotransport in the renal thick ascending limb) e. If the solutes move in opposite directions across the cell membranes, it is called counter-transport, exchange, or antiport (Na+–Ca2+ exchange and Na+–H+ exchange)

SECONDARY ACTIVE TRANSPORT Example of Na+–glucose co-transport • a. The carrier for Na+–glucose co transport is located in the

luminal membrane of intestinal mucosal and renal proximal tubule cells.

• b. Glucose is transported “uphill”; Na+ is transported “downhill.”

• c. Energy is derived from the “downhill” movement of Na+. The inwardly directed Na+ gradient is maintained by the Na+–K+ pump on the basolateral (blood side) mem-brane.

• Poisoning the Na+–K+ pump decreases the transmembrane Na+ gradient and consequently inhibits Na+–glucose cotransport.

Secondary active transportExample of Na+–Ca2+ counter transport or exchange a. Many cell membranes contain a Na+–Ca2+ exchanger that

transports Ca2+ “uphill” from low intracellular [Ca2+] to high extracellular [Ca2+]

. Ca2+ and Na+ move in opposite directions across the cell membrane

b. The energy is derived from the “downhill” movement of Na+.As with cotransport, the inwardly directed Na+ gradient is maintained by the Na+–K+ pump.

Poisoning the Na+–K+ pump therefore inhibits Na+–Ca2+ exchange

Osmosis

A. Osmolarity ■ is the concentration of osmotically active particles in a solution. ■ is a colligative property that can be measured by freezing point depression.

■ can be calculated using the following equation: Osmolarity = g x C where: Osmolarity = concentration of particles (osm/L) • g = number of particles in solution (osm/mol) • C = concentration (mol/L)

■ Two solutions that have the same calculated osmolarity are isosmotic ■ If two solutions have different calculated osmolarities, the solution with the higher osmolarity is hyper-osmotic ■ the solution with the lower osmolarity is hyposmotic.

■ Osmosis is the flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration.

1. Example of osmosis: a. Solutions 1 and 2 are separated by a

semipermeable membrane. Solution 1 contains a solute that is too large to cross the membrane. Solution 2 is pure water. The presence of the solute in solution 1 produces an osmotic pressure

b. The osmotic pressure difference across the membrane causes water to flow from solution 2 (which has no solute and the lower osmotic pressure) to solution 1 (which has the solute and the higher osmotic pressure).

c. With time, the volume of solution 1 increases and the volume of solution 2 decreases

Calculating osmotic pressure (van’t Hoff’s law)

• a. The osmotic pressure of solution can be calculated by van’t Hoff’s law,

• which states that osmotic pressure depends on the concentration of osmotically active particles.

• The concentration of particles is converted to pressure according to the following equation:

• π = g x c x RT• π =osmotic pressure (mm Hg or atm)• g = number of particles in solution (osm/mol) • C = concentration (mol/L) • R = gas constant (0.082 L—atm/mol—K) • T = absolute temperature (K).

• b. The osmotic pressure increases when the solute concentration increases

(A solution of 1 M CaCl2 has a higher osmotic pressure than a solution of 1 M KCl because the concentration of particles is higher)

c. The higher the osmotic pressure of a solution, the greater the water flow into it.

d. Two solutions having the same effective osmotic pressure are isotonic because no water flows across a semipermeable membrane separating them. If two solutions sep-arated by a semipermeable membrane have different effective osmotic pressures, the solution with the higher effective osmotic pressure is hypertonic and the solution with the lower effective osmotic pressure is hypotonic, Water flows from the hypotonic to the hypertonic solution.

• e. Colloidosmotic pressure, or oncotic pressure, is the osmotic pressure created by proteins (e.g., plasma proteins).

Reflection coefficient (σ)

is a number between zero and one that describes the ease with which a solute permeates a membrane.

a. If the reflection coefficient is one, the solute is impermeable. Therefore, it is retained in the original solution, it creates an osmotic pressure, and it causes water flow. Serum albumin (a large solute) has a reflection coefficient of nearly one.

b. If the reflection coefficient is zero, the solute is completely permeable. Therefore, it will not exert any osmotic effect, and it will not cause water flow. Urea (a small solute) has a reflection coefficient of close to zero and it is, therefore, an ineffective osmole.

• 4. Calculating effective osmotic pressure Effective osmotic pressure is the osmotic ■

pressure (calculated by van’t Hoff’s law) multiplied by the reflection coefficient.

■ If the reflection coefficient is one, the solute will exert maximal effective osmotic pres-sure. If the reflection coefficient is zero, the solute will exert no osmotic pressure.

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