CHAP-3-CELL

Cell Membranes

One universal feature of all cells is an

outer limiting membrane called the plasma

membrane.

In addition, all eukaryotic cells contain

elaborate systems of internal membranes

which set up various membrane-enclosed

compartments within the cell.

Cell membranes are built from lipids and

proteins.

Chapter 3: STRUCTURES and FUNCTIONS of the

CELL

Anatomy of a Cell

Plasma Membrane

phospholipid bilayer

specializations:

microvilli

membrane junctions: tight

junctions,

desmosomes

gap junctions

The plasma membrane serves as the interface between the machinery in the interior of the cell and the extracellular fluid (ECF) that bathes all cells.

The lipids in the plasma membrane are chiefly phospholipids like phosphatidyl ethanolamine and cholesterol. Phospholipids are amphiphilic with the hydrocarbon tail of the molecule being hydrophobic; its polar head hydrophilic. As the plasma membrane faces watery solutions on both sides, its phospholipids accommodate this by forming a phospholipid bilayer with the hydrophobic tails facing each other.

functions of plasma membrane

protects cellular contents

makes contact with other cells

contains channels, transporters...

mediates the entry and exit of

substances

FLUID MOSAIC MODEL

Integral Membrane Proteins

Many of the proteins associated with the plasma membrane are tightly bound to it.

Some are attached to lipids in the bilayer.


In others - the transmembrane proteins - the polypeptide chain actually traverses

the lipid bilayer. The figure shows a

transmembrane protein that passes just

once through the bilayer and another that

passes through it 7 times. All G-protein-

coupled receptors (e.g., receptors of

peptide hormones, and odors each span

the plasma membrane 7 times.


In all these cases, the portion within the lipid bilayer consists primarily of

hydrophobic amino acids. These are

usually arranged in an alpha helix so that

the polar -C=O and -NH groups at the

peptide bonds can interact with each other

rather than with their hydrophobic

surroundings.


Those portions of the polypeptide that project out from the bilayer tend to have a

high percentage of hydrophilic amino

acids. Furthermore, those that project into

the aqueous surroundings of the cell are

usually glycoproteins, with many

hydrophilic sugar residues attached to the

part of the polypeptide exposed at the

surface of the cell.


Some transmembrane proteins that span the bilayer several times form a

hydrophilic channel through which certain

ions and molecules can enter (or leave) the

cell

Peripheral Membrane Proteins

These are more loosely associated with the membrane. They are usually attached

noncovalently to the protruding portions of

integral membrane proteins.

Membrane proteins are often restricted in

their movements.

A lipid bilayer is really a film of oil. Thus we might expect that structures immersed in it

would be relatively free to float about. For

some membrane proteins, this is the case.

For others, however, their mobility is

limited:


their movements.

Some of the proteins exposed at the interior face of the plasma membrane are

tethered to cytoskeletal elements like

actin microfilaments.

Some proteins are the exterior face of the plasma membrane are anchored to

components of the extracellular matrix like

collagen.


their movements.

Integral membrane proteins cannot pass through the tight junctions found between

some kinds of cells (e.g., epithelial cells).

Cytoplasm

cellular contents between plasma

membrane & nucleus

2 components:

cytosol

organelles

Cytoplasmic Structures & Organelles

Cytoskeleton: protein filaments

microfilaments

intermediate filaments

microtubules

maintains shape, general

organization & cell integrity

responsible for movement of cell

Cytoplasm

cellular contents between plasma

membrane & nucleus

2 components:

cytosol

organelles

Cytoskeleton

protein filaments

microfilaments

intermediate filaments

microtubules

maintains shape , gen. organization &

cell integrity

responsible for movements of cell

Centrosome

pericentriolar area plus paired

centrioles

9 + 0 array of microtubules

The Centrosome

The centrosome is

located in the cytoplasm attached to the outside of the nucleus.

Just before mitosis, the centrosome duplicates.

The two centrosomes move apart until they are on opposite sides of the nucleus.

As mitosis proceeds, microtubules grow out from each centrosome with their plus ends growing toward the metaphase plate. These clusters of microtubules are called spindle fibers.

The Centrosome

microtubules growing in vitro from an isolated centrosome. The centrosome was supplied with a mixture of alpha and beta tubulin monomers. These spontaneously assembled into microtubules only in the presence of centrosomes.

Spindle fibers have three destinations:

Some attach to one kinetochore of a dyad with those growing from the opposite centrosome

binding to the other kinetochore of that dyad.

Some bind to the arms of the chromosomes.

Still others continue growing from the two centrosomes until they extend between each

other in a region of overlap.

serve as centers for organizing

microtubules

for forming the mitotic spindle

for formation and regeneration of cilia and

flagella

Centrioles

Each centrosome contains a pair of centrioles.

Centrioles are built from a cylindrical array of 9 microtubules, each of which has

attached to it 2 partial microtubules.

Centrioles

When a cell enters the cell cycle, and proceeds from G1 to S phase, each centriole

is duplicated. A "daughter" centriole grows

out of the side of each parent centriole.

Thus centriole replication like DNA replication (which is occurring at the same

time) is semiconservative.

Centrioles

Once formed, most of the functions of the centrosomes can be accomplished without centrioles. However,

Centrioles appear to be needed to organize the centrosome in which they are embedded.

Sperm cells contain a pair of centrioles; eggs have none. The sperm's centrioles are absolutely essential for forming a centrosome which will form a spindle enabling the first division of the zygote to take place.

Centrioles are also needed to make cilia and flagella.

Centrioles

Once formed, most of the functions of the centrosomes can be accomplished without centrioles.

However, Centrioles appear to be needed to organize the centrosome in which they are embedded.

Sperm cells contain a pair of centrioles; eggs have none. The sperm's centrioles are absolutely essential for forming a centrosome which will form a spindle enabling the first division of the zygote to take place.

Centrioles are also needed to make cilia and flagella.

Cilia and Flagella

motile cell surface projections

9 + 2 array of microtubules

basal body

cilia ensure steady flow of fluid along the

cells surface

flagella move the entire cell

Both cilia and flagella have the same basic structure. If the cell has

many short ones, we call them cilia or

only one or a few long ones, we call them flagella.

Each cilium (or flagellum) is made of

a cylindrical array of 9 evenly-spaced microtubules, each with a partial

microtubule attached to it. This gives the

structure a "figure 8" appearance when

view in cross section.

2 single microtubules run up through the center of the bundle, completing the so-

called "9+2" pattern.

The entire assembly is sheathed in a membrane that is simply an extension of

the plasma membrane.

Motion of cilia and flagella is created by the microtubules sliding past one another Link. This requires:

motor molecules of dynein, which link adjacent microtubules together, and

the energy of ATP.

Each cilium or flagellum grows out from, and remains attached to, a basal body

embedded in the cytoplasm. Basal bodies

are identical to centrioles and are, in fact,

produced by them.

Ribosome

composed of rRNA and many ribosomal

proteins

high content of ribonucleic acid

2 subunits : 40 S & 60 S

2 forms of ribosomes:

free ribosomes

bound ribosomes

synthesize proteins

Endoplasmic Reticulum

membranous network of flattened sacs

and tubules

2 forms;

rough ER

smooth ER

synthesize proteins for secretion

forms new membranes

synthesize CHO, phospholipids, fats &

steroids

for detoxification

Golgi Complex

flattened membranous sacs called

cisterns

modifies, sorts packages and transport

products received from ER

forms secretory vesicles

forms peroxisomes

Lysosomes

membrane enclosed vesicle

40 different kinds of hydrolytic enzymes

pH 5

phagocytosis

autophagy

autolysis

Peroxisomes

formed by division of pre existing

peroxisomes

contain enzymes that can oxidize

organic substances

Peroxisomes are also called

microbodies.

oxidize amino acids and fatty acids

oxidize toxic substances

contains catalase that decomposes

H2O2

Peroxisomes

Peroxisomes

Peroxisomes are about the size of lysosomes (0.51.5 m) and like them are bound by a single membrane.

They also resemble lysosomes in being filled with enzymes.

Peroxisomes

Peroxisomes

The enzymes and other proteins destined for peroxisomes are synthesized in the

cytosol. Each contains a peroxisomal

targeting signal (PTS) that binds to a

receptor molecule that takes the protein

into the peroxisome and then returns for

another load.

Peroxisomes

Peroxisomes

Two peroxisomal targeting signals have been identified:

a 9-amino acid sequence at the N-terminal of the protein;

a tripeptide at the C-terminal.

Peroxisomes

Peroxisomes

Each has its own receptor to take it to the peroxisome. Some of the functions of the

peroxisomes in the human liver:

Breakdown (by oxidation) of excess fatty acids.

Breakdown of hydrogen peroxide (H2O2), a potentially dangerous product of fatty-acid

oxidation. It is catalyzed by the enzyme

catalase. [Link to further discussion]

Peroxisomes

Peroxisomes

Participates in the synthesis of cholesterol. One of the enzymes involved, HMG-CoA

reductase, is the target of the popular

cholesterol-lowering "statins".

Participates in the synthesis of bile acids.

Participates in the synthesis of the lipids used to make myelin.

Breakdown of excess purines (AMP, GMP) to uric acid.

Lysosomes and Peroxisomes

Lysosomes

Lysosomes are roughly spherical bodies bounded by a single membrane. They are

manufactured by the Golgi apparatus


Lysosomes

They contain over 3 dozen different kinds of hydrolytic enzymes including

proteases

lipases

nucleases

polysaccharidases


Lysosomes

The pH within the lysosome is about pH 5, substantially less than that of the cytosol

(~pH 7.2). All the enzymes in the lysosome

work best at an acid pH. This reduces the

risk of their digesting their own cell if they

should escape from the lysosome


Lysosomes

At one time, it was thought that lysosomes were responsible for killing cells

scheduled to be removed from a tissue; for

example, the resorption of its tail as the

tadpole metamorphoses into a frog. This is

incorrect. These examples of programmed

cell death (PCD) or apoptosis take place by

an entirely different mechanism


Lysosomes

Materials within the cell scheduled for digestion are first deposited within lysosomes. These may

be:

other organelles, such as mitochondria, that have ceased functioning properly and have been

engulfed in autophagosomes

food molecules or, in some cases, food particles taken into the cell by endocytosis

foreign particles like bacteria that are engulfed by neutrophils

Lysosomes and

Peroxisomes

Lysosomes


Lysosomes

Lysosomal Storage Diseases

Lysosomal storage diseases are caused by the accumulation of macromolecules (proteins,

polysaccharides, lipids) in the lysosomes

because of a genetic failure to manufacture an

enzyme needed for their breakdown. Neurons of

the central nervous system are particularly

susceptible to damage.

Most of these diseases are caused by the inheritance of two defective alleles of the gene

encoding one of the hydrolytic enzymes.


Lysosomes


Examples:

Tay-Sachs disease and Gaucher's disease both caused by a failure to produce an enzyme needed

to break down sphingolipids (fatty acid

derivatives found in all cell membranes).


Lysosomes


Examples:

Mucopolysaccharidosis I (MPS-I). Caused by a failure to synthesize an enzyme (-L-iduronidase) needed to break down proteoglycans like heparan

sulfate. In April 2003, the U.S. Food and Drug

Administration approved a synthetic version of

the enzyme, laronidase (Aldurazyme), as a

possible treatment. This enzyme (containing 628

amino acids) is manufactured by recombinant

DNA technology.


Lysosomes


Examples:

However, one lysosomal storage disease, I-cell

disease ("inclusion-cell disease"), is caused by a

failure to "tag" (by phosphorylation) all the

hydrolytic enzymes that are supposed to be

transported from the Golgi apparatus to the

lysosomes. Lacking the mannose 6-phosphate

(M6P) tag, they are secreted from the cell instead.


Lysosomes

Secretory Lysosomes

In some cells, lysosomes have a secretory function releasing their contents by exocytosis.

Cytotoxic T cells (CTL) secrete perforin from lysosomes.


Lysosomes

Mast cells secrete some of their many mediators of inflammation from modified lysosmes.

Melanocytes secrete melanin from modified lysosomes.

The exocytosis of lysosomes provides the additional membrane needed to quickly seal

wounds in the plasma membrane.

Mitochondria

shoe or sausage-shaped organelles

bounded by two membranes

powerhouse / energy currency

generate ATP

Nucleus

spherical / oval shaped

most prominent

surrounded by a nuclear envelope

controls cellular structure

directs cellular activities

The Nucleus

The nucleus is the hallmark of eukaryotic cells; the very term eukaryotic means

having a "true nucleus". The Nuclear

Envelope

The Nucleus

Chromatin

The nucleus contains the chromosomes of the cell. Each chromosome consists

of a single molecule of DNA complexed

with an equal mass of proteins.

The Nucleus

Chromatin Collectively, the DNA of the nucleus with its

associated proteins is called chromatin. Most

of the protein consists of multiple copies of 5

kinds of histones. These are basic proteins,

bristling with positively charged arginine and

lysine residues. (Both Arg and Lys have a

free amino group on their R group, which

attracts protons (H+) giving them a positive

charge.) Just the choice of amino acids you

would make to bind tightly to the negatively-

charged phosphate groups of DNA.

The Nucleus Chromatin

Chromatin also contains small amounts of a wide variety of nonhistone proteins. Most of these are transcription

factors (e.g., the steroid receptors) and their association

with the DNA is more transient.

Chromatin

loose network of bumpy threads

found in the nucleus

forms chromosomes in a dividing cell

Nucleolus

small, dark-staining round bodies

site for ribosome assembly

Nucleolus

During the period between cell divisions, when the chromosomes are in their extended state, 1 or more of them (10 in human cells) have loops extending into a spherical mass called the nucleolus. Here are synthesized three (of the four) kinds of RNA molecules (28S, 18S, 5.8S) used in the assembly of the large and small subunits of ribosomes.

Nucleolus

28S, 18S, and 5.8S ribosomal RNA is transcribed (by RNA polymerase I) from hundreds to

thousands of tandemly-arranged rDNA genes

distributed (in humans) on 10 different

chromosomes. The rDNA-containing regions of

these 10 chromosomes cluster together in the

nucleolus.

NUCLEUS

GOLGI

MITOCHONDRIA

ROUGH ER

LYSOSOME

CENTRIOLE

PEROXISOME

SMOOTH ER

NUCLEOLUS

FLAGELLA

CILIA

FLUID MOSAIC MODEL

Cell Physiology

Membrane Transport

Osmosis

movement of water molecules across a

selectively permeable membrane

from higher concentration to lower

concentration

solvent and water in living systems

Tonicity = tension

isotonic

hypotonic

hypertonic

Tonicity & Its Effects on RBC

Passive Transport Processes

Diffusion

random movement due to intrinsic

kinetic energy

movement is down a concentration

gradient ( downhill)

Diffusion through the lipid bilayer

passive diffusion of a substance

through the plasma membrane

substances transported:

non-polar hydrophobic solutes

oxygen & carbon dioxide

nitrogen

fatty acids & steroids

fat soluble vitamins

glycerol, small alcohols, NH3

Diffusion through membrane channels

passive diffusion of a substance down

its electrochemical gradient

through channels

some channels are open all the time

while some are gated

Substances transported:

small inorganic solutes

K+, Na+, Cl- & Ca+2

DIFFUSION THRU MEMBRANE

CHANNELS

Facilitated Diffusion

passive but mediated transport

transport is down a concentration

gradient

transmembrane proteins act as

transporters

maximum diffusion rate is limited by

number of transporters

transports polar or charged solutes,

glucose, fructose, galactose, urea and

some vitamins

FACILITATED DIFFUSION

Filtration

movement of water and solutes through

a membrane or capillary wall by

hydrostatic pressure

pressure gradient

transports solute-containing fluid

( filtrate)

Active Transport Processes

mediated transport

energy

against its concentration gradient

transmembrane proteins act as

transporters

Primary Active Transport

solute pumps

transport of a substance against its

concentration gradient

transmembrane proteins that use ATP

Ex. Na+ & K+ pump

transports Na+, K+, Ca+2, Cl- & other

ions

Primary Active Transport a. In primary active transport, energy derived from ATP changes the

shape of a transporter protein, which pumps a substance across a plasma membrane against its concentration gradient.

b. The most prevalent primary active transport mechanism is the sodium ion/potassium ion pump

Secondary Active Transport

coupled transport of 2 substances

energy supplied by a Na+ or H+

concentration gradient

antiporters = opposite direction

symporters = same direction

Substance transported;

antiporters: Ca+2 & H+ out of cells

symporters; glucose, amino acids

into the cell

Secondary Active Transport a. In secondary active transport, the energy stored in the form of a sodium or

hydrogen ion concentration gradient is used to drive other substances against their own concentration gradients.

b. Plasma membranes contain several antiporters and symporters powered by the sodium ion gradient

Digitalis slows the sodium ion-calcium ion antiporters, allowing more calcium to stay inside heart muscle cells, which increases the force of their contraction and thus strengthens the heartbeat

Vesicular Transport A vesicle is a small membranous sac formed by

budding off from an existing membrane

movement of substances into or out of

the cell in vesicles

ATP

2 Kinds:

1. Endocytosis

2 Exocytosis

Endocytosis

phagocytosis

transports bacteria, viruses, aged

or dead cells

pinocytosis

transports solutes in extracellular

fluid

In endocytosis, materials move into a

cell in a vesicle formed from the plasma

membrane.

Receptor-mediated

endocytosis is the

selective uptake of

large molecules

and particles by

cells

Phagocytosis is the ingestion of solid particles

Pinocytosis is the ingestion of extracellular fluid

Exocytosis

transports neurotransmitters, hormones & digestive enzymes

In exocytosis, membrane-enclosed structures called secretory vesicles that form inside the cell fuse with the plasma membrane and release their contents into the extracellular fluid

CELL DIVISION and CELL CYCLE

INTERPHASE

Prophase

PROMETAPHASE

METAPHASE

ANAPHASE

Telophase

Chromatids arrive at opposite poles of cell, and new membranes form around the daughter nuclei. The chromosomes disperse and are no longer visible under the light microscope. The spindle fibers disperse, and cytokinesis or the partitioning of the cell may also begin during this stage.

Cytokinesis

In animal cells, cytokinesis results when a fiber ring composed of a protein called actin around the center of the cell contracts pinching the cell into two daughter cells, each with one nucleus. In plant cells, the rigid wall requires that a cell plate be synthesized between the two daughter cells.

CELLULAR DIVERSITY

DISORDERS: HOMEOSTATIC

IMBALANCES

A. Cancer is a group of diseases characterized by uncontrolled cell proliferation.

1. Cells that divide without control develop into a tumor or neoplasm

2. A cancerous neoplasm is called a malignant tumor or malignancy. It has the ability to undergo

metastasis, the spread of cancerous cells to other

parts of the body. A benign tumor is a noncancerous

growth.


IMBALANCES

Types of Cancer 1. Carcinomas arise from epithelial cells.

2. Melanomas are cancerous growths of melanocytes

3. Sarcomas arise from muscle cells or connective tissues

4. Leukemia is a cancer of blood-forming organs

5. Lymphoma is a cancer of lymphatic tissue.


IMBALANCES

Growth and Spread of Cancer 1. Cancer cells divide rapidly and

continuously.

2. They trigger angiogenesis, the growths of new networks of blood vessels.

3. Cancer cells can leave their site of origin and travel to other tissues or organs, a process

called metastasis.


IMBALANCES

Causes of Cancer 1. Environmental agents can cause cancer growth. A

chemical agent. or radiation that produces cancer is termed a carcinogen and induces mutations in DNA.

2. Viruses can cause cancer.

3. Cancer-causing genes, or oncogenes, can cause cancer.

a. The normal counterparts of oncogenes are called proto-oncogenes; these are found in every cell and carry out normal cellular functions until a malignant change occurs via a mutation.

b. Some cancers may also be caused by genes called anti-oncogenes or tumor-suppressor genes. These genes may produce proteins that normally oppose the action of an oncogene or inhibit cell division.


IMBALANCES

Carcinogenesis is a multistep process involving mutation of oncogenes and anti-

oncogenes; as many as 10 distinct

mutations may have to accumulate in a cell

before it becomes cancerous

Treatment of Cancer

1. Treatment of cancer is difficult because it

is not a single disease and because all the

cells in a tumor do not behave in the same way.

2. Various treatments include surgery, chemotherapy, and radiation therapy

PROTEIN SYNTHESIS

PROTEIN SYNTHESIS

DNA - deoxyribonucleic acid

found in the nucleus controls the function and structures of the cell genes are segments of DNA each gene controls the synthesis of one protein

(generally)

proteins are composed of amino acids arranged in specific sequences - polypeptide chains

each amino acid is synthesised by a set of three nucleotides called a codon

PROTEIN SYNTHESIS Steps in Protein Synthesis:

Much of the cellular machinery is devoted to synthesizing large numbers of diverse proteins. 1. The proteins determine the physical and

chemical characteristics of cells.

2. The instructions for protein synthesis is found in the DNA in the nucleus.

3. Protein synthesis involves transcription and translation

PROTEIN SYNTHESIS DNA "unzips" - a segment of the double helix

uncoils and separates to allow mRNA to be formed

mRNA leaves the nucleus

mRNA attaches to a ribosome on the endoplasmic reticulum

each tRNA segment brings a specific amino acid (present in the cytoplasm) to the mRNA

each tRNA can only link with a specific amino acid

when all of the sites on the mRNA are occupied by complementary segments of RNA, the protein folds to form its specific characteristic shape

some proteins need to go to the Golgi apparatus to complete their synthesis

PROTEIN SYNTHESIS

Steps in Protein Synthesis:

STEP 1: The first step in protein synthesis is the transcription of mRNA from a DNA gene in the

nucleus. At some other prior time, the various

other types of RNA have been synthesized using

the appropriate DNA. The RNAs migrate from the

nucleus into the cytoplasm.Prior to the beginning

of the protein synthesis, all of the component

parts are assembled in the ribosome

Transcription is the process by which

genetic information

encoded in DNA is

copied onto a strand

of RNA called

messenger RNA

(mRNA), which directs

protein synthesis

PROTEIN SYNTHESIS

Besides serving as the template for the synthesis of mRNA, DNA also synthesizes

two other kinds of RNA, ribosomal RNA

(rRNA), and transfer RNA (tRNA).

b. Transcription of DNA is catalyzed by RNA polymerase.

c. Antisense therapy that blocks mRNA has been approved by the FDA

PROTEIN SYNTHESIS

Translation 1. Translation is the process of reading the

mRNA nucleotide sequence to determine the

amino acid sequence of the protein

PROTEIN SYNTHESIS

STEP 2: Initiation:

In the cytoplasm, protein synthesis is actually initiated by the AUG codon on mRNA. The AUG codon signals both the interaction of the ribosome with m-RNA and also the tRNA with the anticodons (UAC). The tRNA which initiates the protein synthesis has N-formyl-methionine attached. The formyl group is really formic acid converted to an amide using the -NH2 group on methionine (left most graphic)

PROTEIN SYNTHESIS

some proteins are exported as enzymes, hormones, etc

some proteins are necessary for the cell's function

some are used to produce membranes or the structures on membranes

PROTEIN SYNTHESIS

STEP 2: Initiation:

The next step is for a second tRNA to approach the mRNA (codon - CCG). This is the code for proline. The anticodon of the proline tRNA which reads this is GGC. The final process is to start growing peptide chain by having amine of proline to bond to the carboxyl acid group of methinone (met) in order to elongate the peptide

PROTEIN SYNTHESIS

STEP 3: Elongation: Elongation of the peptide begins as various tRNA's

read the next codon. In the example on the left the next tRNA to read the mRNA is tyrosine. When the correct match with the anticodons of a tRNA has been found, the tyrosine forms a peptide bond with the growing peptide chain .

The proline is now hydrolyzed from the tRNA. The proline tRNA now moves away from the ribosome and back into the cytoplasm to reattach another proline amino acid.

PROTEIN SYNTHESIS

Step 4: Elongation and Termination:

When the stop signal on mRNA is reached, the protein synthesis is terminated. The last amino acid is hydrolyzed from its t-RNA.

The peptide chain leaves the ribosome. The N-formyl-methionine that was used to initiate the protein synthesis is also hydrolyzed from the completed peptide at this time.

The ribosome is now ready to repeat the synthesis several more times.

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