Course 2

The structural and functional

organization of the cell
• The cell and its functions
The human body contains about 100 trillion
cells, each of which represents a living
structure that survives indefinitely and can
reproduce when it has proper conditions. The
cell has two main components: the nucleus
and the cytoplasm. The nucleus has a nuclear
membrane that separates it from the
cytoplasm, and it is bounded by the
surrounding environment through the cell
membrane. In addition to these two important
components, the cell also contains various
substances and these are called protoplasm.
Protoplasm consists of: water, electrolytes,
proteins, lipids, carbohydrates.
The cell membrane

• The membrane contains mainly lipids and proteins. Protein molecules

often penetrate the entire membrane, disrupting the lipid barrier, thus
forming transmembrane pathways or channels through which various
substances will pass. Lipids will form a barrier to water and other
substances that would move between the cell compartments.
The cell membrane has a bilipid layer, in fact a thin lipid film two molecules thick and
arranged continuously at the periphery. Between these two layers are the globular proteins.
The lipids are cholesterol and phospholipids. Some of them are soluble only in lipids,
forming the hydrophobic part and others are soluble in water, being the hydrophilic part.
The hydrophilic portions are positioned on the outside where they come in contact with the
surrounding water and the hydrophobic ones line up in the center.This bilipid layer is a real barrier
for water-soluble substances such as urea, glucose, ions, instead they can pass the fat-soluble ones
such as carbon dioxide, oxygen, alcohol.The bilipid layer has a liquid character, so proteins or other
dissolved substances can diffuse over the entire surface of the membrane.
The globular masses in the bilipid layer represent the membrane proteins formed mainly by
glycoproteins. There are two categories: whole proteins and peripheral proteins.
Integral proteins will form channels (pores) through which water-soluble substances pass.
These channels are selective, achieving a differentiated diffusion for some substances.Peripheral
proteins are attached to the inner faces of the membrane without crossing it. They are attached to
one of the whole proteins. They act as enzymes that catalyze chemical reactions that are very
important for the cell function. In addition to these proteins, the membrane also has some carrier proteins.
They deal with the "active transport" of substances (in the opposite direction to the natural diffusion).
The carbohydrates of the cell membrane- the glycocalyx
If we talk about the glycoproteins and glycolipids of the cell membrane, it means that it
contains, in addition to proteins and lipids, carbohydrates in combination with them.The glycoproteins
represent the large majority of integral proteins. At the level of the cell membrane, carbohydrates
protrude to the outside.Other carbohydrate compounds called proteoglycans have a protein core that
hangs from the outer surface of the membrane.
The functions of carbohydrates are:
1. They give the cell surfaces a negative charge
2. Solidify the cells together (glycocalyx of two cells can attach)
3. Activate whole proteins by acting as hormone-binding receptors (insulin)
4. Participate in immune reactions.
THE CYTOPLASM AND ITS ORGANITES
The five organs of the cytosol are:
- the endoplasmic reticulum
- the Golgi apparatus
- mitochondria
- lysosomes
- peroxisomes.
The endoplasmic reticulum consists of a network of tubular and flattened vesicular structures that
are interconnected. The walls are made up of lipids and proteins. Inside the tubes is a liquid medium
other than the cytosol - the endoplasmic matrix. The endoplasmic reticulum has a very important role
in the metabolic activity of the cell, presenting numerous enzymes attached to its membranes.
Small granular particles called ribosomes are attached to the outer face of its membrane.
The endoplasmic reticulum-ribosome assembly represents the rough or granular endoplasmic
reticulum. Part of the reticulum has no ribosomes, it is called the smooth or agranular endoplasmic
reticulum.
The Golgi apparatus consists of four or more overlapping layers of thin vesicles.
It has close relations with the endoplasmic reticulum, the membranes being similar to its own and
functioning in association with it.
The lysosomes are an intracellular digestive system through which the cell removes unwanted substances
(bacteria) through digestion. They are formed in the Golgi apparatus, then dispersed in the cytoplasm.
Lysosomes have a diameter of 250-750 nm and the lysosomal membrane is bilipid with protein aggregates
in its structure. Digestion will result in amino acids from proteins and glycogen will be hydrolyzed to
glucose. The main substances digested are: proteins, nucleic acids, mucopolysaccharides, lipids and
glycogen. More than 50 different acid hydrolases have been found in lysosomes, with the lysosomal
membrane preventing them from meeting cytoplasmic elements.
The mitochondria
They extract large amounts of energy from oxygen and food.
They are spread throughout the cytoplasm and may number in the hundreds or thousands, depending
on the needs of each cell type. Composed mainly of two bilipid protein membranes, internal and
external and matrix. The inner membrane has folds forming septa or ridges to which oxidative enzymes
are attached. The matrix is ​the inner cavity of the mitochondria and contains many dissolved enzymes.
These enzymes work together with the enzymes on the septa of the inner membrane causing the
oxidation of the food principles from which CO2 and H2O result. The resulting energy is used in the
synthesis of adenosine triphosphate (ATP) which is the way the whole cell uses energy.
THE NUCLEUS
The nucleus remains the most important intracellular part. It is the control center of the cell.
It contains large amounts of DNA (genes) that will determine the characteristics of cytoplasmic enzymes,
influencing its functions. The genes also intervene in reproduction, being the first to divide within the
mitosis with the formation of daughter cells, each of them receiving one of the two sets of genes.
The nucleus is clearly outlined and well delimited by the cytoplasm through the nuclear membrane.
It is very easy to see under a microscope in a living cell because it has a different refractive index than
the cytoplasm. The nucleus has chromatin scattered throughout the nucleoplasm and it forms
chromosomes during mitosis.
The nuclear membrane is double, one component being inside and one outside.
The outer membrane is a continuation of the endoplasmic reticulum, so the space between the two
membranes is a continuation of the space inside the endoplasmic reticulum. This shell is crossed by
thousands of large nuclear pores, passing molecules with high and low molecular weight.
The endocytosis
The cellular ingestion food principles cross the cell membrane by active transport and diffusion.
When the cell is in contact with larger particles, they are introduced into the cell through a special
function - endocytosis. This includes pinocytosis and phagocytosis.
Pinocytosis occurs continuously through the membranes of many cells, in addition in some cells, this process
has a special speed.
Proteins usually bind to each type of specific receptor. At the surface of the membrane the places
with receptors are called coated pits which have in their thickness a fibrillar-clathrin protein and actin
and myosin filaments. As soon as the protein touches the receptor closes the edges like a bag, then comes
off the surface of the membrane being a pinocytosis vesicle. This process is performed with the help of
actin and myosin in the structure, but also with an energy consumption in the form of ATP.
Phagocytosis involves the ingestion of large particles and only a few cells have this ability
(macrophages, leukocytes). Phagocytic particles have proteins or mucopolysaccharides on their surface
that will come in contact with phagocyte receptors. Bacteria are usually encapsulated in specific antibodies
and are attached to phagocyte receptors. This phenomenon demonstrated by the role of antibodies in
phagocytosis is called opsonization. Stages of phagocytosis:
- The ligands on the surface of the phagocytic particle bind to the receptors
- all the contractile elements participate in this process
- the contractile proteins carry the vesicles formed in the membrane, towards the inside of the cell.
Intracellular Digestion of Foreign Substances
- Lysosomes When phagocytosis or pinocytosis vesicles reach the cell, lysosomes attach to them and
release their specific enzymes - acid hydrolases. In this way, the digestive vesicle was born, where
the acid hydrolysis of nucleic acids, proteins, glycogen, mucopolysaccharides takes place.
- Digestion results in amino acids, phosphates, glucose, and what remains undigested in the blisters
are the residual bodies that will be eliminated from the cell by exocytosis. Another important role
of the lysosomes is to destroy phagocytosed microbial bactericidal substances before they cause
damage. Among the bactericidal substances are: lysozyme (dissolves membranes), lysoferrin
(binds important metals for the growth of bacteria), in addition it has an acid pH of about 5 which
activates its own enzymes and inactivates bacterial systems.
The endoplasmic reticulum and the Golgi system-the richest cells in the endoplasmic
reticulum and Golgi apparatus are the secretory ones. Usually the synthesis begins in the endoplasmic
reticulum, then the products pass into the Golgi apparatus where they undergo processing before
being released. Lipid synthesis takes place in the smooth endoplasmic reticulum -the rough (granular)
endoplasmic reticulum has ribosomes with a role in protein formation. After the protein molecule is
synthesized, it passes through the membrane of the endoplasmic reticulum into its matrix where it is
processed by the enzymes of the reticulum. Proteins synthesized by ribosomes and released into the
cytoplasm are free proteins, and those in the R.E. are mostly glycoproteins. Golgi can form certain
carbohydrates that R.E. can’t. These are sialic acid and galactose.
FUNCTIONS OF MITOCHONDRIA-ENERGY EXTRACTION
sources such as: oxygen, carbohydrates, lipids, proteins. Even before they reach the cells, carbohydrates
are converted into glucose, proteins into amino acids and lipids into fatty acids. The food principles
inside the cell react with oxygen, all oxidative reactions taking place in the mitochondria and the
energy released is stored as ATP which will be used in turn in metabolic reactions.
EXCHANGES OF SUBSTANCES THROUGH CELL MEMBRANES
If we take the cell as a reference, we can talk about the intracellular and extracellular fluid, which
will include the interstitial fluid (in the spaces between the cells), but also the blood plasma.
The introduction into the cells of the substances necessary for the cellular activity, as well as the
elimination of the products of catabolism or metabolically useful ones is achieved through transmembrane
transport phenomena, of a great diversity and efficiency. The extracellular fluid is rich in sodium and
chlorine, but very low in potassium, while the intracellular fluid has the exact opposite situation containing
more potassium, protein and phosphates
Located at the boundary between the cell and the extracellular environment, the cell membrane controls
and modulates the exchanges, ensuring the survival, functioning and permanent homeostatic adaptation
of the cells to the environmental conditions.
The bilipid layer of the cell membrane is a barrier to the movement of water and water-soluble
substances between the extracellular and intracellular space. Membrane proteins that cross the lipid
layer are an alternative transport pathway, and are called transport proteins. Some whole proteins can
create homogeneous hydrophilic pathways that cross the membrane like a tunnel, called protein (ionic)
channels, and others are called carrier proteins that help substances cross the cell membrane.
Two types of mechanisms:
- passive transport - in the sense of transmembrane physico-chemical
gradients, without energy consumption (osmosis and diffusion)
- active transport - against transmembrane physico-chemical gradients, with energy consumption
Diffusion represents the chaotic molecular motion of substances, either through intermolecular
spaces in the membrane or in combination with a transporter protein. The energy that causes diffusion
is the kinetic energy resulting from movement.Due to the movement of molecules, electrostatic and
internuclear forces attract and repel, moving in different directions, bouncing randomly millions of
times per second.This permanent movement of molecules is called diffusion.At the level of the cell
membrane we are talking about two important subtypes of diffusion: simple and facilitated
The simple diffusion
- the possibility of crossing the membrane determined by the amount of existing substance,
the speed of kinetic movement and the number of membrane pores through which molecules or
ions pass - can follow two paths: through the lipid bilayer or through protein hydrophilic channels.
Diffusion of fat-soluble substances
The rate at which a substance passes through the lipid bilayer depends on the liposubility of that substance.
Oxygen, carbon dioxide, nitrogen, alcohol are soluble
in the lipid layer, have a high diffusion rate and penetrate quickly into the cell.
Transmembrane water transport by simple diffusion
Membrane lipids are hydrophobic, but water crosses the cell membrane fairly quickly, most passing through
protein channels. The water molecules are small enough and their kinetic energy is high enough that
they pass quickly before being stopped by hydrophobic lipids.
Ions cannot cross the lipid bilayer freely.Each ion transport is done through protein channels because
the ions have an electric charge and the lipid bilayer has polarized lipids with negative charges that
will repel the ions. The interaction between the electric charge of the ion and the charge of the lipid
bilayer makes it possible for them to cross the membrane only through its protein channels.
Simple diffusion
Ionic channels. The ionic channels are characterized by permeability and selectivity. The selectivity of the
channel allows the passage of only certain ionic species due to "selectivity barriers". The permeability
of the channel, the ability to ensure an ionic flow is achieved by a barrier mechanism
("gating mechanism").It is described: 1 -dependent voltage channels, with voltage sensors which,
when reaching a difference in transmembrane potential, make intrachanical load shifts; 2 –chemically
dependent channels that open in the presence of certain endo- or exogenous substances; 3 –changed
receptor channels - some proteins of the channel gate are opened as a result of the fixation of other
molecules on these proteins, producing a conformational change of the protein molecule that closes
and opens the gate. This is called "ligant gating", and the substance that binds is called ligand
(chemical messenger); 4-mechanically-activated channels - under the influence of mechanical factors
(pressure, tension) go through conformational changes that open them; 5 -channels with spontaneous
opening
The voltage-dependent channel conducts current according to the "all or nothing" law. Closing and
opening the gate is sudden, the time required to switch from one state to another being of the order
of a few millionths of a second. At a certain voltage the channel can remain closed all the time, while
at another voltage level it can remain open all the time.
Na + voltage dependent channels appear mainly in the neuronal membranes and in the
skeletal muscle. Under the action of a stimulus there is an influx of cations and a depolarization
occurs in that area which if it exceeds the threshold(- 10 - 15 mv) changes the charge at the membrane
surface and causes a redistribution of electrons inside.This flow of electrons inwards results in a change
in the state of the barriers. The phenomenon is called gating current.
-depolarization of the membrane decreases the channel opening threshold (hyperexcitability), and
hyperpolarization increases this threshold (low excitability). This voltage-dependent mechanism is
the model of the action potentials of the nerves, which in fact represent the nerve impulses.
K + voltage dependent channels have a single permeability barrier that opens late the sodium channels
activated by the same stimulus are already inactive.Once in the open position, the K + channels play
the role of a passive waterway, through which, under the influence of the concentration gradient, a
K + efflux is achieved carrying an ionic current directed in the opposite direction to the Na + current
through the specific channels mentioned above.This current increases the transmembrane potential
difference.
Ca + voltage-dependent channels control a good part of the Ca + transmembrane flows, with special
implications in triggering and modulating a wide range of cellular activities.The channel protein
consists of five polypeptide and glycopeptide subunits: alpha1, alpha2, beta on the inner face,
gamma, delta on the outer side.
Facilitated diffusion is a form of passive transport that is mediated by carriers and involves the presence
of a specific carrier protein that helps to cross the membrane at a much higher speed than simple
diffusion. The diffusion rate reaches a maximum as the concentration increases. The molecule to be
transported is fixed on the “cis” end of the protein, then follows the actual transport stage, in which the
movement through the inside of the transporter towards the opposite “trans” face takes place.
In this way glucose and most amino acids are transported. If the glucose
concentration on the "trans" face is reduced, the unloaded transporter returns to the "cis" face to
attach a new molecule.Glucose has a molecule that can carry other monosaccharides and insulin can
increase the rate of facilitated diffusion of glucose 10-20 times.
Counter-transport- also called carrier-mediated exchange, it is an alternative to the facilitated diffusion
mechanism.The return stage of the unloaded conveyor from the "trans" face to the "cis" face is missing.
They are part of a series of transporter proteins such as: the Na + / Ca2 + exchanger (in neural and
myocardial membranes) and the Na + / H + one.
The net diffusion rate in one direction represents the difference in the amounts of substance diffusing in
the two directions.
Factors that affect this rate are: 1-membrane surface 2-permeability 3-concentration difference of
diffusing substances 4-potential difference between the two sides of the membrane 5-pressure
difference
Osmosis in the cell membrane
The transmembrane movement of water molecules is achieved by the phenomenon of osmosis.
In the case of two solutions separated by a semipermeable membrane, the solvent (water) molecules
will move from the low-concentration (solvent) compartment to the high-concentration compartment.
In solutions with lower concentration, the solvent molecules being less obstructed by the solvate, have
a higher molecular agitation, passing into the high concentration zone.
Osmolality. Osmotic pressure.
A concentration of 1 osmol per liter will determine in solution an osmotic pressure of 19,300 mmHg,
at the normal body temperature of 37 ° C. The 300 milliosmol concentration of body fluids causes an
osmotic pressure of 5790 mmHg.
Active transport
The transmembrane transport of substances against physical gradients, as well as the maintenance of
ionic concentration inequalities (sodium and potassium) cannot be explained unless the existence of
active transport mechanisms (pumps) is taken into account. Active transports can be of two types,
primary and secondary, depending on the energy source used for the transport and how it is performed.
Primary active transport is characterized by the fact that it uses ATP directly for transport, which is
achieved with the help of ATPases specific to each ionic species or molecule transported. In secondary
active transport, the energy of an ionic concentration gradient is used, previously generated by primary
active transport.
The primary active transport benefits from sodium, potassium, calcium, hydrogen, chlorine and other
ions.The best known of the active transport mechanisms is that of sodium and potassium called
the sodium-potassium pump with ATP .
As a result of the processes that take place, sodium dissociates to the outside of the cell and
potassium enters the cell.The pump can be found in all cells of the body and regulates the
transmembrane concentration gradients of sodium and potassium, achieving a negative electrical
potential inside the cell.
Operating at full capacity, this ATPase carries three sodium ions outward and two potassium ions
inward for each molecule of hydrolyzed ATP. Phosphorylation and cyclic dephosphorylation of the
protein makes it oscillate between two alternative conformations (molecular peristalsis).
SODIUM CO-TRANSPORT OF GLUCOSE AND AMINO ACIDS
In many cells, glucose and amino acids are transported against the concentration gradient.
After sodium and glucose have been fixed, the carrier protein undergoes a conformational change and
then is transported simultaneously in the cell.Sodium Amino Acid co-transport uses other carrier
proteins, but happens similarly. There are five types of amino acid transport proteins, each carrying a
subset of amino acids. These examples of co-transport are present in renal tubular cells and intestinal
mucosa cells.
COUNTER-TRANSPORT SODIUM-HYDROGEN AND SODIUM-CALCIUM
As a result of this mechanism, sodium is moved to the inside of the cell and calcium to the outside of
the cell.The calcium antiport is present in all cell membranes, both ions having the same carrier protein.
This mode of transport adds to the mechanism of calcium transport in some cells.Sodium-hydrogen
countertransport is very important in the proximal convoluted tubules of the nephron, where as sodium
moves out of the lumen, hydrogen ions leave the cell.