Cell Physiology

Lesson 1 in physiology

centrioles

Located in the core of Centrosome

These are paired cylindrical bodies perpendicular to one another and each composed of nine triplets of microtubule.

The organize a microtubule network during mitosis to form the spindle and asters they also form the bases of cilia and flagella.

testosterone

Crucial for mood, sleep, certain bodily functions in males

glucocerebrosidase

important for moving large molecules within the blood. If there is a deficiency it can lead to a build of large proteins.

Cell

Are the basic structural and functional units of life. All living organisms are cellular in nature, including amoebas with only one or human, animals and big plants with many. It has 3 main regions: the plasma membrane, the cytoplasm, and the nucleus.

Plasma membrane

Is the outer thin and flexible membrane of the cell which separates the intracellular from extracellular compartment (fluid). It is made of a double layer of lipids such as phospholipids, cholesterol and glycolipids within which proteins are embedded.

Functions:

1. Serves as an external cell barrier against substances and forces outside the cell

2. Externally facing proteins act as receptors for hormones, neurotransmitters, etc., and in cell-to-cell recognition.

3. Acts in the transport of substances into or out of the cell.

Phospholipids

are the most abundant lipids in the plasma membrane.

The heads are hydrophilic (attached to water, the main constituent of intra and extra cellular fluids) and lie along the inner and outer face of the membrane.

The Tails are hydrophobic ( avoid water and line up in the center of the membrane)

Membrane proteins

integral proteins and peripheral proteins

Integral proteins

are the most abundant proteins in the membrane most extend entirely through the membrane (transmembrane) but some protrude from one side of the membrane they could act as receptors.

Peripheral proteins

are mainly on the cytoplasmic side. They support cytoplasmic side of the membrane by a network of filaments.

Glycocalyx

it is a sugar covering or cell coat: produced by corneal epithelial surface cells it is used to help bind mucins onto the corneal surface. It is a short chain of carbohydrate sugars projected out from the external surface of glycoprotein or glycolipids this functions in cell to cell binding and recognition.

Passive process

substances can pass freely through the lipid bilayer down their concentration gradient from more concentrated region to the less concentrated region. No energy (ATP) is needed.

Diffusion

Movement of small, uncharged molecules like oxygen, Co2 and fat soluble molecules across the membrane.

Active process

substances move against a concentration gradient from a lower to a higher concentration, ATP is needed.

Active transport

most larger water soluble or charged molecules such as glucose, amino acids and ions are transported by a pump or carrier and involve the integral proteins.

Vesicular transport

Also known as bulk transport are large particles and macromolecules pass through the membrane by this mechanism. There are generally two types of bulk transport: exocytosis and endocytosis.

Exocytosis

Membrane lined cytoplasmic vesicles fuse with the plasma membran and release their contents to the outside of the cell. Mucus and protein secretions from the glands in the body. Proteins extending from the vesicle membrane vSNAREs, bind with plasma membrane proteins known as the t SNAREs )T FOR TARGET), THIS CAUSES THE LIPID LAYERS OF THE VESICLE and cell membrane to join together.

Endocytosis

Brings large molecules into the cell through an initial infolding part of the plasma membrane that encloses them to form cytoplasmic vesicles. Clathrin protein, found on the cytoplasmic side of the infolding is responsible for deforming the membrane.

There are 3 types

phagocytosis, pinocytosis and

receptor-mediated endocytosis

Phagocytosis

(Cell eating) Here, parts of plasma

membrane form

pseudopodes and flow

around large

molecules such as

bacteria or cellular

debris and engulf it.

By this way, a

membranous vesicle,

called a phagosome is

formed.

Phagosomes mostly

fuse to the lysosomes

for enzymatic break

down of

phagosomal contents.

White blood cells have

such phagocytic

activity.

Pinocytosis

(Cell drinking) Is fluid phase endocytosis. a small infolding of the plasma membrane surrounds

a small quantity of extracellular fluid containing dissolved molecules.

This is the main function of cells lining the small intestine, absorption

of the nutrients.

Receptor mediated endocytosis

It is a selective mechanism. Specific

molecules such as insulin and other

hormones, enzymes and low density

lipoproteins (LDL, molecules that

carry cholesterol in the blood to the

body’s cells) are brought into the cells

by first attaching to a receptor on the

membrane before being taken into the

cells in a protein coated vesicle.

Contents of the vesicles are released

by binding to lysosomes and the

receptors are recycled back to plasma

membrane.

Viruses and some toxins use the same

mechanism to enter the cells.

Familial Hypercholesterolemia

Is an inherited disease in which the cells lack the receptors that bind to

cholesterol binding LDLs.

As a result, cholesterol cannot enter the cells and builds up in the blood,

causing hypercholesterolemia and atherosclerosis which lead to stroke or

myocardial infarction.

Cytoplasm

Cytoplasm is the cellular

region between the nucleus

and plasma membrane.

It consists of:

cytosol, or cytoplasmic

matrix which is a viscous

fluid containing water,

ions and enzymes,

inclusions containing

stored nutrients and

pigments and organelles.

Ribosomes

Ribosomes:

-Are dark staining granules with

no membrane.

-Ribosomes are site of protein

production.

They consist of two subunits:

protein and ribosomal RNA

(rRNA, ribonucleic acid).

Free ribosomes make the protein

used in the cytosol.

Ribosomes attached on the

surface of rER make the proteins

used for cell membrane

or exported out of the cell.

Amino acids on the ribosomes are

linked together to form protein.

This process is

called Translation and is dictated

by DNA of the nucleus. Such

instructions are

carried to the ribosomes by

messengers called messenger

RNA (mRNA).

Rough endoplasmic reticulum

Is a ribosome-studded system of membrane-walled envelopes in cytosol, called cisternae.

Ribosomes on the rER make proteins which enter the cisternae and are secreted

by the cell in vesicles.

Ribosomes also make the proteins of the cell membrane.

Smooth Endoplasmic reticulum

Is a network of membranous system of sacs and tubules in the cytosol.

It has no ribosomes and is involved in the synthesis of lipids and steroids,

lipid metabolism and drug detoxification.

Golgi Apparatus

Is a stack of 3-10 disc-shaped envelopes or cisternae which are bound by membrane.

Cisternae have a cis (convex) and a trans (concave) face.

It sorts the products of rER and packs them in membrane bound vesicles and sends

them to their proper destination.

Secretory granules and lysosomes also arise from this.

Mitochondria

Are rod like organelles covered by two membranes in the cytoplasm.

The inner membrane is folded into projections called cristae.

Mitochondria are the main energy generator of the cell and are the

main site of ATP synthesis.

Lysosomes

Are spherical, membrane-walled sacs containing digestive enzymes called

Acid hydrolases.

Lysosomes are site of intracellular digestion and they destroy (digest)

deteriorated organelles and substances brought into the cells by vesicles.

They fuse with phagosomes and empty their enzymes into phagosomes,

breaking down their contents. Phagocytic cells have a lot of lysosomes.

Tay sachs disease

is an inherited disease,

infants lack specific enzymes in the

lysosomes responsible for break down of

certain glycolipids. As a result, glycolipids

accumulate in the cell membrane specially

on neurons, resulting in mental slowing,

blindness, spastic movements and death

within 1.5 years from birth.

Gaucher’s disease

The lack of the glucocerebrosidase enzyme causes harmful substances to build up in

the liver, spleen, bones, and bone marrow. The substances prevent cells and organs

from working properly.

There are three main subtypes:

1.Type 1 disease is most common. It involves bone disease, anemia, an enlarged

spleen and thrombocytopenia. Type I affects both children and adults.

2.Type 2 disease usually begins in infancy with severe neurologic involvement. This

form can lead to rapid, early death.

3.Type 3 disease may cause liver, spleen, and brain problems. Patients may live into

adulthood.

Symptoms

Symptoms vary depending on the type of disease, but may include:

Bone pain and fractures

Enlarged spleen

Enlarged liver

Lung disease

Seizures

Peroxisomes

Are membrane-walled, enzyme-containing sacs.

They contain oxidase and catalase enzymes.

Oxidases use oxygen to neutralize aggressively reactive substances called

free radicals, by converting them to hydrogen peroxide.

Hydrogen peroxide, although reactive and dangerous, it is converted to oxygen

and water by catalases which break down poisons like alcohol, phenol and

formaldehydes that have entered the body. Liver and kidney have many peroxisomes.

Cytoskeleton

Is a network of rods running throughout the cytosol to support the cellular structure

and generates movements of the cell. There are 3 types of such cytoskeleton:

Microtubules, microfilaments and intermediate filaments

Cell skeleton

Microtubules

Are cylindrical structures made of tubulin proteins. They radiate out from the

centrosome region close to the nucleus. They give the cell its shape and they organize

the distribution and transport of various organelles within the cytoplasm.

Microfilaments

(actin filaments) Are fine filaments of

contractile protein called

actin. They are labile.

Actin interacts with another

protein called myosin, and

generates contractile forces

within the cell. It is involved

in muscle contraction, and

other types of cellular

movements such as

amoeboid movements and

extension of pseudopods.

Intermediate filaments

are tough

insoluble and stable protein

fibers

which act to resist tension

placed on the cell.

Centrosome

is a spherical structure in the

cytoplasm near the nucleus. It consists of

an outer cloud of protein called: matrix

and an inner pair of centrioles.

Matrix protein is involved in the elongation

of microtubules and mitotic spindle of

microtubules radiates from it in dividing

cells.

Cytoplasmic inclusions

Impermanent structures in the cytoplasm

such as lipid droplets and glycogen

containing glycosomes.

Centrioles

are in the core of centrosome.

These are paired cylindrical bodies

perpendicular to one another and each

composed of nine triplets of microtubules.

They organize a microtubule network

during mitosis to form the spindle and asters.

They also form the bases of cilia

and flagella

Nucleus

is the control center of the cell

and contains genetic materials (DNA),

which directs the cell’s activities by

providing the instructions for protein

synthesis.

Most cells have one nucleus in the center,

some have multiple nuclei e.g.: skeletal

muscle, however, mature red blood cells

have no nucleus (anucleate) at all.

Main parts:

1- Nuclear envelope

2- Chromatin and chromosomes

3- Nucleoli

Nuclear envelope

Surrounds the nucleus and has pores and

is continuous with endoplasmic reticulum.

Nucleolus

Is a dark staining body within the nucleus.

It contains parts of chromosomes and is

cell’s ribosome producing machine (has

genes that code for rRNA)

Chromatin

is the granular thread-like

material in the nucleus composed of DNA

(Deoxyribonucleic acid)

and histone proteins.

DNA constitute the genes.

genetic code is copied onto mRNA in a

process called transcription

Deoxyribonucleic acid

DNA molecule in chromatin is a double

helix chains of nucleotide molecules.

*Nucleotides consist of sugar, phosphate and

one of four bases: thymine (T), adenine (A),

cytosine (C) or guanine (G), which bind to

hold the DNA helix together like a ladder.

*DNA helix wraps around clusters of eight

spherical proteins called histones, which

regulate gene expression and transcription.

*Each cluster of DNA and histones is called

a nucleosome.

Chromosomes

contains a single, very long

molecule of DNA. There are 46 chromosomes

in a typical human cell.

*Chromatin is distributed in chromosomes.

During cell division, the chromatin is highly

coiled, making the chromosomes appear as

thick rods.

Cell life cycle

is a series of changes

a cell experiences from the time it forms

until it reproduces itself.

The cycle has two major periods:

1- Interphase, in which the cell grows

and carries on its usual activities,

2- Cell division (mitotic phase), during

this period, the cell divides into 2 cells.

*Cell division is essential for growth and

repair of the body.

Interphase

Is the non-dividing phase of the cell cycle,

cells maintain their life-sustaining activities

and prepare for the next cell division.

It consists of subphases G1, S and G2.

Gap 1

Cells are active and grow vigorously and

centrioles start to replicate.

Synthetic phase

DNA replicates itself for the future two

daughter cells having identical genetic

material.

Gap 2

Enzymes needed for cell division are

synthesized, centrioles finish replication

and cell gets ready to divide.

Mitosis

Has four stages:

1- prophase

2- metaphase

3- anaphase

4- telophase

Prophase

First phase, Asters (stars) are formed; these are microtubule arrays, extending from the centrosome.

*Chromosomes are formed from coiling and condensation of the chromatin threads.

(each chromosome has 2 identical chromatin threads, now called chromatids;

the chromatids are held together by centromere and a protein complex called cohesin.)

nucleoli disappear centriole pairs separate *nuclear envelope fragments

*microtubules disassemble and are newly assembled to form mitotic spindles which lengthen

and push the centrioles farther apart to the poles of the cell (some of these spindles are

attached to chromosomes and are called kinetochores; others are called polar spindles).

Metaphase

Second phase, Chromosomes cluster at the middle of the cell,

to form a metaphase plate.

*Separase, an enzyme which cleaves

cohesin, start to separates the chromatids.

Anaphase

Third phase, *the V-shaped chromatids are pulled apart

by the kinetochore spindles to become the

chromosomes of the daughter cells, and the

polar spindles still push against each other

to elongate the cell.

This stage lasts for few minutes only.

Telophase

Fourth phase, This phase is like prophase in reverse.

*chromosomes at the opposite sides of the cell

uncoil and resume extension of the chromatin.

*nuclear envelope forms by rER.

*nucleoli appear.

**For a short period, the cell has 2 nuclei until

it is completely separated by the process of

CYTOKINESIS

Meiosis

is a specialized process of cell division that occurs only in the production of

gametes. It consists of two divisions that result in the formation of four gametes, each

containing half the number of chromosomes (23 single chromosomes) and half the

amount of DNA (1N) found in normal somatic cells (46 single chromosomes, 2N).

Meiosis 1

Synapsis: pairing of 46 homologous duplicated chromosomes.

*Crossing over: large segments of DNA are exchanged.

Alignment: 46 homologous duplicated chromosomes align at the metaphase plate.

Disjunction: 46 homologous duplicated chromosomes separate from each other;

centromeres do not split.

Cell division: two secondary gametocytes (23 duplicated chromosomes, 2N) are

formed.

Meiosis 2

Synapsis: absent

Crossing over: absent

Alignment: 23 duplicated chromosomes align at the metaphase plate.

Disjunction: 23 duplicated chromosomes separate to form 23 single chromosomes;

centromeres split.

Cell division: four gametes (23 single chromosomes, 1N) are found.

Trisomy

21 chromosomes, Down syndrome

Klinefelter syndrome

XXXY chromosomes

Turner syndrome

Monosomy (XO)

Gametes

contain 23 single chromosomes (22 autosomes and 1 sex chromosome) and

1N amount of DNA.

The term “haploid” is classically used to refer to a cell containing 23 single

chromosomes.

*Female gametes contain only the X sex chromosome.

*Male gametes contain either the X or Y sex chromosome; therefore, the male

gamete determines the genetic sex of the individual.

Mitochondrial theory of aging

involves a decrease of energy production by

radical-damaged mitochondria which weakens and ages the cell. Vitamins C and E

act as antioxidants and prevent excessive production of free radicals. The same is

true with caloric intake restriction due to lowering the metabolic rate which slows

aging.

Genetic theories of aging

proposes that aging is programmed into our genes

(senescence)

Apoptosis

(Programmed cell death) is the method whereby cells are removed from tissues in an orderly fashion

as a part of normal maintenance or during development.

1. Cells that undergo programmed cell death have several morphological features.

-They include chromatin condensation, breaking up of the nucleus, and the plasma

membrane.

- The cell shrinks and is fragmented into membrane-enclosed fragments called

apoptotic bodies.

2. The signals that induce apoptosis may occur through several mechanisms.

- Certain cytokines, such as tumor necrosis factor (TNF), may also activate

caspases that degrade regulatory and structural proteins in the nucleus and

cytoplasm, leading to the morphological changes characteristic of apoptosis.

3. Defects in the process of programmed cell death contribute to many major diseases.

- Too much apoptosis causes extensive nerve cell loss in Alzheimer disease and

stroke.

- Insufficiency of apoptosis has been linked to cancer and other autoimmune

disease.

Cancer

cell mass which divides and multiplies abnormally; it is also called a neoplasm.

Neoplasms are classified as Benign or Malignant.

Benign neoplasm

or tumor is a local mass, remains compacted, often encapsulated, grows

slowly and seldom kills the host.

Malignant neoplasm

or cancer is a mass which is not-capsulated and grows rapidly.

Cells here are immature and they invade their surrounding.

These give metastasis (invading other tissues) by means of lymphatics and/or blood.

Oncogenes

are the result of mutations of certain regulatory genes, called protooncogenes,

which normally stimulate or inhibit cell proliferation and development.

1. Genetic accidents or viruses may lead to the formation of oncogenes.

2. Oncogenes dominate the normal alleles (proto-oncogenes), causing deregulation of cell

division, which leads to a cancerous state.

3. Bladder cancer and acute myelogenous leukemia are caused by occogenes.